EOS Med Chem, Medicinal Chemical is Big: new -1

CAT NO

CHEMICAL NAME

CASRN

SYNONYMS

Formula

MWt

SMILES

Solubility

Clinical Information

Research Area

Biological Description

Target

Pathway

Library

References list

References link list

EOS XFZ-00001

Fenoterol (hydrobromide)

1944/12/3

Fenoterol bromide;Th-1165a;Phenoterol hydrobromide

C17H22BrNO4

384.2649

[H]Br.OC1=CC(C(O)CNC(C)CC2=CC=C(O)C=C2)=CC(O)=C1

DMSO：≥ 38 mg/mL

Launched

Inflammation/Immunology

Fenoterol hydrobromide is a β 2 adrenergic agonist designed to open up the airways to the lungs, is classed as sympathomimetic β2 agonist and asthma medication.

Adrenergic Receptor

GPCR/G protein

FDA-approved_Drug_Library; GPCR/G protein Compound Library; MCE online Bioactive Compound Library

EOS XFZ-00002

Guanidine (hydrochloride)

1950/1/1

Guanidinium chloride;Aminoformamidine Hydrochloride

CH6ClN3

95.53144

NC(N)=N.Cl

10 mM in DMSO

Launched

Metabolic Disease

Guanidine HCl, the crystalline compound of strong alkalinity formed by the oxidation of guanine, is a normal product of protein metabolism and a protein denaturant. Target: Others Guanidine HCl is the most popular protein denaturant. Analysis of unfolding transitions by Guanidine HCl provides several important parameters regarding the mechanism of conformational stability of proteins. Guanidine HCl at low concentrations refolds acid-unfolds apomyoglobin and cytochrome c, stabilizing the molten globule state. Guanidine HCl (> 1 M) causes co-operative unfolding of the molten globule state [1]. Guanidine HCl at millimolar concentrations, is able to causes efficient loss of the normally stable [PSI+] element from yeast cells. 5 mM Guanidine HCl in growth media cures [PSI+] and other prions of yeast. 5 mM Guanidine HCl significantly reduces Hsp104-mediated basal and acquired thermotolerance by 30-fold and 50 fold, respectively. Guanidine HCl also reduces the ability of Hsp104 to restore activity of thermally denatured luciferase [2].

Others

FDA-approved_Drug_Library; MCE online Bioactive Compound Library

[1] Hagihara, Y., et al., Guanidine hydrochloride-induced folding of proteins. J Mol Biol, 1993. 231(2): p. 180-4. [2] Jung, G. and D.C. Masison, Guanidine hydrochloride inhibits Hsp104 activity in vivo: a possible explanation for its effect in curing yeast prions. Curr Microbiol, 2001. 43(1): p. 7-10.

[1] http://www.ncbi.nlm.nih.gov/pubmed/8389881 [2] http://www.ncbi.nlm.nih.gov/pubmed/11375656

EOS XFZ-00003

Dexamethasone

1950/2/2

MK 125;NSC 34521;Prednisolone F

C22H29FO5

392.4611

O=C1C=C[C@@]2(C)C(CC[C@]3([H])[C@]2(F)[C@@H](O)C[C@@]4(C)[C@@]3([H])C[C@@H](C)[C@@]4(C(CO)=O)O)=C1

DMSO: ≥ 56 mg/mL

Launched

Inflammation/Immunology

Dexamethasone is a glucocorticoid receptor agonist. IC50 & Target: Glucocorticoid receptor[1] In Vitro: Dexamethasone regulates several transcription factors, including activator protein-1, nuclear factor-AT, and nuclear factor-kB, leading to the activation and repression of key genes involved in the inflammatory response[1]. Dexamethasone potently inhibits granulocyte-macrophage colony stimulating factor (GM-CSF) release from A549 cells with EC50 of 2.2 nM. Dexamethasone (EC50=36 nM) induces transcription of the β2-receptor is found to correlate with glucocorticoid receptor (GR) DNA binding and occurred at 10-100 fold higher concentrations than the inhibition of GM-CSF release. Dexamethasone (IC50=0.5 nM) inhibits a 3×κB (NF-κB, IκBα, and I-κBβ), which is associated with inhibition of GM-CSF release[2]. In Vivo: It has previously been reported that treatment with Dexamethasone at a dose of 2×5 mg/kg efficiently inhibits lipopolysaccharide (LPS)-induced inflammation. In our experimental system, treatment with a single dose of Dexamethasone 10 mg/kg (i.p.) significantly decreases recruitment of granulocytes as well as spontaneous production of oxygen radicals compared with animals expose to LPS and injected with solvent alone (saline). The effects are statistically significant when administered both 1 h before and 1 h after inhalation of LPS. The number of granulocytes in BALF decreased to levels comparable to healthy animals (given an aerosol of water)[3]. Rats treated with Dexamethasone consume less food and weighed less than control rats. Treated rats also weigh less than pair-fed animals though their food intake is similar. Five days of Dexamethasone injection result in a significant increase in both the liver mass (+42%) and the liver to body weight ratio (+65%). The wet weight of gastrocnemius muscle decreases 20% after 5 days of treatment, but it remains unaffected relative to body weight (g/100 g body weight), indicating that muscle weight loss paralleled body weight loss[4].

Autophagy; Glucocorticoid Receptor

Autophagy; GPCR/G protein

Autophagy Compound Library; FDA-approved_Drug_Library; GPCR/G protein Compound Library; MCE online Bioactive Compound Library

[1] J Mullol, A Xaubet, E López, Comparative study of the effects of different glucocorticosteroids on eosinophil survival primed by cultured epithelial cell supernatants obtained from nasal mucosa and nasal polyps. Thorax. 1995 March; 50(3): 270-274. [2] Leskiewicz M, Jantas D, Regulska M, Antidepressants attenuate the dexamethasone-induced decrease in viability and proliferation of human neuroblastoma SH-SY5Y cells: A involvement of extracellular regulated kinase (ERK1/2). Neurochem Int. 2013 Jul 29. pii: S0197-0186(13)00202-7. [3] Heberden C, Meffray E, Goustard-Langelier B, Dexamethasone inhibits the maturation of newly formed neurons and glia supplemented with polyunsaturated fatty acids. J Steroid Biochem Mol Biol. 2013 Jul 29. pii: S0960-0760(13)00139-8. [4] Lu XX, McCoy KS, Hu WK, Dexamethasone reduces IL-17 and Tim-3 expression in BALF of asthmatic mice. J Huazhong Univ Sci Technolog Med Sci. 2013 Aug;33(4):479-84. [5] Wyns H, Meyer E, Watteyn A, Pharmacokinetics of dexamethasone after intravenous and intramuscular administration in pigs. Vet J. 2013 Jul 19. pii: S1090-0233(13)00299-2.

[1] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1021191/ [2] http://www.ncbi.nlm.nih.gov/pubmed/23906970 [3] http://www.ncbi.nlm.nih.gov/pubmed/23907015 [4] http://www.ncbi.nlm.nih.gov/pubmed/23904364 [5] http://www.ncbi.nlm.nih.gov/pubmed/23876308

EOS XFZ-00004

Hydrocortisone (acetate)

1950/3/3

Hydrocortisone 21-acetate

C23H32O6

404.4966

C[C@@]12[C@](C(COC(C)=O)=O)(O)CC[C@@]1([H])[C@]3([H])CCC4=CC(CC[C@]4(C)[C@@]3([H])[C@@H](O)C2)=O

DMSO: ≥ 38 mg/mL

Launched

Inflammation/Immunology

Hydrocortisone acetate is a corticosteroid, used to decrease swelling, itching, and pain that is caused by minor skin irritations or by hemorrhoids.

Glucocorticoid Receptor

GPCR/G protein

FDA-approved_Drug_Library; GPCR/G protein Compound Library; MCE online Bioactive Compound Library

EOS XFZ-00005

Cortisone (acetate)

1950/4/4

Cortisone 21-acetate

C23H30O6

402.4807

C[C@@]1(C2)[C@](C(COC(C)=O)=O)(O)CC[C@@]1([H])[C@]3([H])CCC4=CC(CC[C@]4(C)[C@@]3([H])C2=O)=O

DMSO: 6.8 mg/mL (Need ultrasonic and warming)

No Development Reported

Cancer

Cortisone acetate (17-hydroxy-11-dehydrocorticosterone), a 21-carbon steroid hormone, is one of the main hormones released by the adrenal gland in response to stress. IC50 Value: Target: Glucocorticoid Receptor in vitro: Cortisone suppressed this apoptosis at a concentration range of 1-10,000 ng/ml (2.8-28,000 nM) dose-dependently. Suppression of cortisol-induced apoptosis by cortisonewas consistently observed in PBMCs derived from 16 healthy subjects. Examination for inhibitory activities of the steroids against [3H]dexamethasone binding to PBMCs suggested that cortisone can bind cellular GC-receptors (GC-Rs), but the affinity of cortisone to GCRs is 1/30 or less than that of cortisol [1]. Apoptosis was also readily induced in primary cultures of third trimester decidual cells when treated with cortisol, cortisone, or dexamethasone (all 100 nM for 24 h) [2]. in vivo: The effects of a single dose of cortisone acetate (5 or 10 mg/100 g body weight) on B cells were examined in young chickens. A dose-dependent increase in numbers of circulating B lymphocytes and a change in their Ig-class distribution were followed by parallel increase in splenic plasma cells and serum immunoglobulins. The higher dose of cortisone produced changes in Bmu and Bgamma cells, whereas the lower dose primarily affected Bmu cells [3]. Adult female CD-1 mice received daily injections of cortisone acetate (0--50 mg/kg subcutaneously) and/or amphotericin B (0--12.5 mg/kg intraperitoneally) in a checkerboard combination dosage pattern for 30 days. Dosages of amphotericin B and cortisone acetate that produced little or no mortality individually produced significant (P less than 0.005) mortality in combination [4]. Toxicity: Oral use of cortisone has a number of potential systemic side-effects: hyperglycemia, insulin resistance, diabetes mellitus, osteoporosis, anxiety, depression, amenorrhoea, cataracts and glaucoma, among other problems.

Glucocorticoid Receptor

GPCR/G protein

Anti-cancer Compound Library; Clinical Compound Library; FDA-approved_Drug_Library; GPCR/G protein Compound Library; MCE online Bioactive Compound Library

[1] Hirano T, et al. Cortisone counteracts apoptosis-inducing effect of cortisol in human peripheral-blood mononuclear cells. Int Immunopharmacol. 2001 Nov;1(12):2109-15. [2] Chan J, et al. Glucocorticoid-induced apoptosis in human decidua: a novel role for 11beta-hydroxysteroid dehydrogenase in late gestation. J Endocrinol. 2007 Oct;195(1):7-15. [3] Rusu VM, et al. In vivo effects of cortisone on the B cell line in chickens. J Immunol. 1975 Nov;115(5):1370-4. [4] Kisch AL, et al. Synergistic nephrotoxicity of amphotericin B and cortisone acetate in mice. J Infect Dis. 1978 Jun;137(6):789-94.

[1] http://www.ncbi.nlm.nih.gov/pubmed/11710540 [2] http://www.ncbi.nlm.nih.gov/pubmed/17911392 [3] http://www.ncbi.nlm.nih.gov/pubmed/1100730 [4] http://www.ncbi.nlm.nih.gov/pubmed/659923

EOS XFZ-00006

Mitomycin C

1950/7/7

Ametycine

C15H18N4O5

334.3272

NC1=C(C(C2=C(C1=O)[C@@H](COC(N)=O)[C@]3(OC)N2C[C@H]4[C@@H]3N4)=O)C

DMSO: 30 mg/mL

Registered

Cancer

Mitomycin C is a DNA-damaging agent and small-molecule inhibitor effectively sensitize cancer cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). IC50 & Target: TNF[1] In Vitro: The HCT116 (p53-/-) cells are minimally sensitive to either Mitomycin C or TRAIL alone. However, surprisingly, combination treatment with MMC and TRAIL decreases cell viability significantly. Although Mitomycin C and TRAIL alone are moderately effective, Mitomycin C substantially enhances the effect of TRAIL on suppression of the cell proliferation. Mitomycin C and TRAIL treatment alone induces 9.5% and 35.0% apoptosis, respectively. However, combination treatment with Mitomycin C and TRAIL enhances apoptosis to 66.6%[1]. Mitomycin C is a cytotoxic chemotherapeutic agent that causes DNA damage in the form of DNA cross-links as well as a variety of DNA monoadducts and is known to induce p53[2]. In Vivo: Mice bearing xenografted HCT116 (p53-/-) colon tumors and HT-29 colon tumors are treated with Mitomycin C (i.p., 1 mg/kg) and TRAIL (i.v., 100 μg) every other day. Animals are treated with 10 consecutive cycles of the combination therapy regimen. The combination therapy suppresses tumor growth significantly and does not impact the weight of the mice, indicating that the therapeutic combination of Mitomycin C and TRAIL is well-tolerated and has anti-tumor activity in vivo[1]. Intravesical Mitomycin C instillations has an effect on body weight that is not observed in normal, NaCl instilled or Epirubicin instilled rats. After 3 consecutive weekly instillations of 1 mg/mL Mitomycin C there is almost no weight gain, whereas rats in the other 3 groups has a statistically significant weight gain compared with MMC treated rats[3].

ADC Cytotoxin; Autophagy; DNA Alkylator/Crosslinker

Antibody-drug Conjugate/ADC Related; Autophagy; Cell Cycle/DNA Damage

Anti-cancer Compound Library; Autophagy Compound Library; Cell Cycle/DNA Damage Compound Library; Clinical Compound Library; MCE online Bioactive Compound Library

[1] Bizanek R, et al. Isolation and structure of an intrastrand cross-link adduct of mitomycin C and DNA. Biochemistry. 1992 Mar 31;31(12):3084-3091. [2] Gorgülü O, et al.  Adjunctive use of mitomycin C in endoscopic revision dacryocystorhinostomy.  B-ENT. 2012;8(2):123-126. [3] Cheng H, et al.  Mitomycin C potentiates TRAIL-induced apoptosis through p53-independent upregulation of death receptors: Evidence for the role of c-Jun N-terminal kinase activation. Cell Cycle. 2012 Sep 1;11(17): 3312-23. [4] Tomasz M, Lipman R, Chowdary D, Pawlak J, Verdine GL, Nakanishi K. Isolation and structure of a covalent cross-link adduct between mitomycin C and DNA. Science. 1987 Mar 6;235(4793):1204-8. [5] Bizanek R, McGuinness BF, Nakanishi K, Tomasz M. Isolation and structure of an intrastrand cross-link adduct of mitomycin C and DNA. Biochemistry. 1992 Mar 31;31(12):3084-91.

[1] http://www.ncbi.nlm.nih.gov/pubmed/1554696 [2] http://www.ncbi.nlm.nih.gov/pubmed/22896931 [3] http://www.ncbi.nlm.nih.gov/pubmed/22895172 [4] http://www.ncbi.nlm.nih.gov/pubmed/3103215 [5] http://www.ncbi.nlm.nih.gov/pubmed/1554696

EOS XFZ-00007

Piperonyl butoxide

1951/3/6

ENT-14250

C19H30O5

338.4385

CCCC1=C(COCCOCCOCCCC)C=C2OCOC2=C1

10 mM in DMSO

Launched

Infection

Piperonyl butoxide is a semisynthetic derivative of safrole，used as a component of pesticide formulations. It is a synergist, despite having no pesticidal activity of its own, it enhances the potency of certain pesticides such as Carbamates, Pyrethrins, Pyrethroids, and Rotenone.

Antiparasitic

Anti-infection

EOS XFZ-00008

Procaine (hydrochloride)

1951/5/8

C13H21ClN2O2

272.771

O=C(OCCN(CC)CC)C1=CC=C(N)C=C1.Cl

10 mM in DMSO

Launched

Neurological Disease

Procaine Hydrochloride is a local anesthetic drug of the amino ester group. Target: Others Procaine is a local anesthetic of the ester type that has a slow onset and a short duration of action.Procaine (0.01-100 microM) inhibited the 5-HT3 receptor-mediated inward current in the whole-cell patch clamp recording. Procaine appears to produce a competitive inhibition on 5-HT3 receptors with a KD of 1.7 microM [1]. Procaine is a DNA-demethylating agent that produces a 40% reduction in 5-methylcytosine DNA content as determined by high-performance capillary electrophoresis or total DNA enzyme digestion. Procaine can also demethylate densely hypermethylated CpG islands. Procaine also has growth-inhibitory effects in these cancer cells, causing mitotic arrest [2]. Procaine functions as an excitant of limbic system cells, and that procaine alters synaptic transmission in some, but not all, output pathways from the amygdale [3].

Others

FDA-approved_Drug_Library; MCE online Bioactive Compound Library

[1] Fan, P. and F.F. Weight, Procaine impairs the function of 5-HT3 receptor-ion channel complex in rat sensory ganglion neurons. Neuropharmacology, 1994. 33(12): p. 1573-9. [2] Villar-Garea, A., et al., Procaine is a DNA-demethylating agent with growth-inhibitory effects in human cancer cells. Cancer Res, 2003. 63(16): p. 4984-9. [3] Adamec, R.E. and C. Stark-Adamec, The effects of procaine HCl on population cellular and evoked response activity within the limbic system of the cat. Evidence for differential excitatory action of procaine in a variety of limbic circuits. Prog Neuropsychopharmacol Biol Psychiatry, 1987. 11(4): p. 345-64.

[1] http://www.ncbi.nlm.nih.gov/pubmed/7539114 [2] http://www.ncbi.nlm.nih.gov/pubmed/12941824 [3] http://www.ncbi.nlm.nih.gov/pubmed/3423267

EOS XFZ-00009

Nialamide

1951/12/7

C16H18N4O2

298.3397

O=C(C1=CC=NC=C1)NNCCC(NCC2=CC=CC=C2)=O

DMSO: ≥ 30 mg/mL

Launched

Neurological Disease

Nialamide is a non-selective, irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class that was used as an antidepressant.

Monoamine Oxidase

Neuronal Signaling

FDA-approved_Drug_Library; MCE online Bioactive Compound Library; Neuronal Signaling Compound Library

EOS XFZ-00010

Spironolactone

1952/1/7

SC9420

C24H32O4S

416.5735

C[C@@]12[C@](OC3=O)(CC3)CC[C@@]1([H])[C@@]([C@@H](CC4=CC5=O)SC(C)=O)([H])[C@]([C@]4(CC5)C)([H])CC2

10 mM in DMSO

Launched

Metabolic Disease

Spironolactone is a potent antagonist of the androgen receptor. Target: Androgen Receptor Spironolactone is a potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. 5% topical spironolactone cream acts as an antiandrogen in human sebaceous glands, competing with DHT receptors and producing a decrease of labelled DHT. At the concentrations used the effect has been only local. No side-effects were recorded during both studies [1]. Patients who received spironolactone had a significant improvement in the symptoms of heart failure, as assessed on the basis of the New York Heart Association functional class (P<0.001). Gynecomastia or breast pain was reported in 10 percent of men who were treated with spironolactone, as compared with 1 percent of men in the placebo group (P<0.001). The incidence of serious hyperkalemia was minimal in both groups of patients [2].

Androgen Receptor; Autophagy

Autophagy; Others

Autophagy Compound Library; FDA-approved_Drug_Library; MCE online Bioactive Compound Library

[1] Berardesca, E., et al., Topical spironolactone inhibits dihydrotestosterone receptors in human sebaceous glands: an autoradiographic study in subjects with acne vulgaris. Int J Tissue React, 1988. 10(2): p. 115-9. [2] Pitt, B., et al., The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med, 1999. 341(10): p. 709-17.

[1] http://www.ncbi.nlm.nih.gov/pubmed/2972662 [2] http://www.ncbi.nlm.nih.gov/pubmed/10471456

EOS XFZ-00011

Tiopronin

1953/2/2

C5H9NO3S

163.1949

O=C(O)CNC(C(S)C)=O

10 mM in DMSO

Launched

Metabolic Disease

Tiopronin is a prescription thiol drug used to control the rate of cystine precipitation and excretion in the disease cystinuria. Target: Others Tiopronin is used primarily for cystinuria and is well known in the cystinuric community. Depending on the severity of a person's cystinuria, tiopronin may be taken for life, possibly starting in early childhood. It may also be used for Wilson's disease (an overload of copper in the body), and certain types of rare arthritis, though tiopronin is not an anti-inflammatory. Tiopronin is also sometimes used as a stabilizing agent for metal nanoparticles. The thiol group binds to the nanoparticles, preventing coagulation [1, 2].

Others

FDA-approved_Drug_Library; MCE online Bioactive Compound Library

[1] http://en.wikipedia.org/wiki/Tiopronin [2] Dahl, J.A., B.L. Maddux, and J.E. Hutchison, Toward greener nanosynthesis. Chem Rev, 2007. 107(6): p. 2228-69.

[1] http://en.wikipedia.org/wiki/Tiopronin [2] http://www.ncbi.nlm.nih.gov/pubmed/17564480

EOS XFZ-00012

Prednisone

1953/3/2

Dehydrocortisone

C21H26O5

358.4281

C[C@@]1(C2)[C@](C(CO)=O)(O)CC[C@@]1([H])[C@]3([H])CCC4=CC(C=C[C@]4(C)[C@@]3([H])C2=O)=O

10 mM in DMSO

Launched

Inflammation/Immunology

Prednisone (Adasone) is a synthetic corticosteroid agent that is particularly effective as an immunosuppressant compound. Target: Others Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases (such as moderate allergic reactions) and (at higher doses) some types of cancer, but has significant adverse effects. Because it suppresses the immune system, it leaves patients more susceptible to infections. Prednisone can also be used in the treatment of decompensated heart failure to potentiate renal responsiveness to diuretics, especially in heart failure patients with refractory diuretic resistance with large dose of loop diuretics. The mechanism is prednisone, as a glucocorticoid, can improve renal responsiveness to atrial natriuretic peptide by increasing the density of natriuretic peptide receptor type A in the renal inner medullary collecting duct, inducing a potent diuresis.

Others

CNS-penetrant Compound Library; FDA-approved_Drug_Library; MCE online Bioactive Compound Library

[1] RIEMER AD. Application of the newer corticosteroids to augment diuresis in congestive heart failure. Am J Cardiol. 1958 Apr;1(4):488-96. [2] Zhang H, et al. Prednisone adding to usual care treatment for refractory decompensated congestive heart failure. Int Heart J. 2008 Sep;49(5):587-95.

[1] http://www.ncbi.nlm.nih.gov/pubmed/13520608 [2] http://www.ncbi.nlm.nih.gov/pubmed/18971570

EOS XFZ-00013

Galanthamine (hydrobromide)

1953/4/4

C17H22BrNO3

368.2655

O[C@@H]1C[C@@H]2OC3=C4C(CN(C)CC[C@]42C=C1)=CC=C3OC.Br

DMSO: ≥ 3.5 mg/mL; DMSO < 7.8 mg/mL

Launched

Neurological Disease

Galanthamine hydrobromide is a long-acting, centrally active acetylcholinesterase(AChE) inhibitor (IC50 = 410 nM) and allosteric potentiator at neuronal nicotinic ACh receptors. IC50 Value: 410 nM Target: AChE Galanthamine hydrobromide prevents β-amyloid-induced apoptosis in SH-SY5Y and bovine chromaffin cells. Long-term administration reduces amyloid precursor protein deposition and neurodegeneration in a mouse model of Alzheimer's disease.

AChE

Neuronal Signaling

FDA-approved_Drug_Library; MCE online Bioactive Compound Library; Neuronal Signaling Compound Library

[1] Arias et al Galantamine prevents apoptosis induced by b-amyloid and thapsigargin: involvement of nicotinic acetycholine receptors. Neuropharmacology (2004) 46 103. [2] Kita Y, Ago Y, Takano E, Fukada A, Takuma K, Matsuda T.Galantamine increases hippocampal insulin-like growth factor 2 expression via α7 nicotinic acetylcholine receptors in mice.Psychopharmacology (Berl). 2012 Aug 30. [3] Berkov S, Viladomat F, Codina C, Suárez S, Ravelo A, Bastida J.GC-MS of amaryllidaceous galanthamine-type alkaloids.J Mass Spectrom. 2012 Aug;47(8):1065-73. [4] Park CW, Son DD, Kim JY, Oh TO, Ha JM, Rhee YS, Park ES.Investigation of formulation factors affecting in vitro and in vivo characteristics of a galantamine transdermal system.Int J Pharm. 2012 Oct 15;436(1-2):32-40. Epub 2012 Jul 5. [5] Park YS, Kim SH, Kim SY, Kim YH, Lee MH, Yang SC, Shaw LM, Kang JS.Quantification of Galantamine in Human Plasma by Validated Liquid Chromatography-Tandem Mass Spectrometry using Glimepride as an Internal Standard: Application to Bioavailability Studies in 32 Healthy Korean Subjects.J Chromatogr Sci. 2012 Jun 28.

[1] http://www.sciencedirect.com/science/article/pii/S0028390803003174 [2] http://www.ncbi.nlm.nih.gov/pubmed/22932776 [3] http://www.ncbi.nlm.nih.gov/pubmed/22899516 [4] http://www.ncbi.nlm.nih.gov/pubmed/22771734 [5] http://www.ncbi.nlm.nih.gov/pubmed/22744744

EOS XFZ-00014

Cortisone

1953/6/5

17-Hydroxy-11-dehydrocorticosterone;Kendall's compound E

C21H28O5

360.444

C[C@@]1(C2)[C@](C(CO)=O)(O)CC[C@@]1([H])[C@]3([H])CCC4=CC(CC[C@]4(C)[C@@]3([H])C2=O)=O

10 mM in DMSO

Launched

Inflammation/Immunology

Cortisone is a 21-carbon steroid hormone. Cortisone is one of the main hormones released by the adrenal gland in response to stress. Target： In chemical structure, it is a corticosteroid closely related to cortisol. It is used to treat a variety of ailments and can be administered intravenously, orally,intraarticularly (into a joint), or transcutaneously. Cortisone suppresses the immune system, thus reducing inflammation and attendant pain and swelling at the site of the injury. Risks exist, in particular in the long-term use of cortisone. Cortisone, a glucocorticoid, and adrenaline are the main hormones released by the body as a reaction to stress. They elevate blood pressure and prepare the body for a fight or flight response.

Others

FDA-approved_Drug_Library; MCE online Bioactive Compound Library

EOS XFZ-00015

L-Nicotine

1954/11/5

(-)-Nicotine;(S)-Nicotine

C10H14N2

162.2316

CN1[C@H](C2=CC=CN=C2)CCC1

10 mM in DMSO

Launched

Others

L-Nicotine is the prototype of nicotinic acetylcholine receptor agonists; natural isomer.

Autophagy; nAChR

Autophagy; Membrane Transporter/Ion Channel; Neuronal Signaling

Autophagy Compound Library; CNS-penetrant Compound Library; FDA-approved_Drug_Library; MCE online Bioactive Compound Library; Membrane Tranporter/Ion Channel Compound Library; Neuronal Signaling Compound Library

EOS XFZ-00016

3,3',5-Triiodo-L-thyronine (sodium)

1955/6/1

T3 Sodium salt;Sodium L-3,3',5-triiodothyronine;Liothyronine sodium

C15H11I3NNaO4

672.9553

[O-]C([C@H](CC1=CC(I)=C(C(I)=C1)OC2=CC=C(O)C(I)=C2)N)=O.[Na+]

DMSO: ≥ 42 mg/mL

Launched

Endocrinology

Liothyronine sodium (T3 Sodium sal) is the most potent form of thyroid hormone used to treat hypothyroidism and myxedema coma. IC50 value: Target: In comparison to levothyroxine (T4), liothyronine has a faster onset of action as well as a shorter biological half-life, which may be due to less plasma protein binding to thyroxine-binding globulin and transthyretin.

Others

FDA-approved_Drug_Library; MCE online Bioactive Compound Library

[1] Liothyronine, From Wikipedia

[1] http://en.wikipedia.org/wiki/Liothyronine

EOS XFZ-00017

Methylthiouracil

1956/4/2

MTU

C5H6N2OS

142.1789

O=C(C=C(C)N1)NC1=S

10 mM in DMSO

Launched

Endocrinology

Methylthiouracil is an antithyroid preparation. Target: Others Methylthiouracil is an antithyroid preparation. It is a thioamide, closely related to propylthiouracil. The drug acts to decrease the formation of stored thyroid hormone, as thyroglobulin in the thyroid gland. The clinical effects of the drug to treat the hyperthyroid state can have a lag period of up to two weeks, depending on the stores of thyroglobulin and other factors. From Wikipedia.

Others

FDA-approved_Drug_Library; MCE online Bioactive Compound Library

[1] http://en.wikipedia.org/wiki/Methylthiouracil

EOS XFZ-00018

6-Acetamidohexanoic acid

1957/8/9

6-Acetamidocaproic acid

C8H15NO3

173.2096

O=C(O)CCCCCNC(C)=O

DMSO: ≥ 1.8 mg/mL

Launched

Others

6-Acetamidohexanoic acid is a pharmaceutical intermediate

Others

FDA-approved_Drug_Library; MCE online Bioactive Compound Library

EOS XFZ-00019

Methotrexate

1959/5/2

Amethopterin;CL14377;WR19039

C20H22N8O5

454.4393

NC1=NC(N)=C2C(N=CC(CN(C)C3=CC=C(C(N[C@@H](CCC(O)=O)C(O)=O)=O)C=C3)=N2)=N1

DMSO: ≥ 30 mg/mL

Pre-registration

Cancer

Methotrexate is a traditional folate antagonist, with median IC50 of 78 nM for a 120 h drug exposure in a panel of six pediatric leukemia and lymphoma cell lines using the sulforhodamine B assay. IC50 & Target: Antifolate[1] In Vitro: Methotrexate (MTX), which has a more predictable toxicity profile than aminopterin, has become a cornerstone of the treatment for childhood acute lymphoblastic leukemia (ALL) and for non-Hodgkins lymphoma[1]. In Vivo: Methotrexate (MTX) exposure reduces thymus and spleen indices of mice. Methotrexate markedly decreases white blood cells, thymic and splenic lymphocytes at dose ≥5 mg/kg. However, there is a significant difference between the treatment plus control group and the model group (p<0.01). The combination of grape seed proanthocyanidins and Siberian ginseng eleutherosides obviously diminishes the effects of Methotrexate exposure on indices of thymus and spleens in mice[2].

ADCs cytotoxin; Antifolate

Antibody-drug conjugates/ADCs Related; Cell Cycle/DNA Damage

Anti-cancer Compound Library; Cell Cycle/DNA Damage Compound Library; Clinical Compound Library; CNS-penetrant Compound Library; FDA-approved_Drug_Library; MCE online Bioactive Compound Library; Toxins for Antibody-drug conjugates research Library

[1] Budzik GP, et al. Effects of methotrexate on nucleotide pools in normal human T cells and the CEM T cell line. Life Sci. 2000;66(23):2297-307. [2] Chen YX, et al. Methotrexate induces apoptosis of human choriocarcinoma cell line JAR via a mitochondrial pathway. Eur J Obstet Gynecol Reprod Biol. 2009 Apr;143(2):107-11. [3] Ohbayashi M, et al. Induction of pulmonary fibrosis by methotrexate treatment in mice lung in vivo and in vitro. J Toxicol Sci. 2010 Oct;35(5):653-61. [4] Padmanabhan S, et al. Cytotoxic and genotoxic effects of methotrexate in germ cells of male Swiss mice. Mutat Res. 2008 Aug-Sep;655(1-2):59-67. [5] Sitzia J, et al. Side effects of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy for breast cancer. Cancer Pract. 1998 Jan-Feb;6(1):13-21.

[1] http://www.ncbi.nlm.nih.gov/pubmed/10855951 [2] http://www.ncbi.nlm.nih.gov/pubmed/19181434 [3] http://www.ncbi.nlm.nih.gov/pubmed/20930460 [4] http://www.ncbi.nlm.nih.gov/pubmed/18678279 [5] http://www.ncbi.nlm.nih.gov/pubmed/9460322

EOS XFZ-00020

Dibucaine (hydrochloride)

1961/12/1

Cinchocaine hydrochloride

C20H30ClN3O2

379.9241

O=C(C1=CC(OCCCC)=NC2=CC=CC=C12)NCCN(CC)CC.Cl

10 mM in DMSO

Launched

Neurological Disease

Dibucaine Hydrochloride is a local anesthetic of the amide type now generally used for surface anesthesia. Target: Sodium Channel Dibucaine is an amide local anesthetic. Dibucaine reduced the degradation of BSA-gold complex in the reservosomes, which was not caused either by an inhibition of the whole proteolytic activity of the parasite or by a reduction on the expression levels of cruzipain [1]. Dibucaine, a quaternary ammonium compound, inhibited SChE to a minimum within 2 min in a reversible manner. The inhibition was very potent. It had an IC(50) of 5.3 microM with BuTch or 3.8 microM with AcTch. The inhibition was competitive with respect to BuTch with a K(i) of 1.3 microM and a linear-mixed type (competitive/noncompetitive) with respect to AcTch with inhibition constants, K(i) and K(I) of 0.66 and 2.5 microM, respectively. Dibucaine possesses a butoxy side chain that is similar to the butryl group of BuTch and longer by an ethylene group from AcTch [2].

Sodium Channel

Membrane Transporter/Ion Channel

FDA-approved_Drug_Library; MCE online Bioactive Compound Library; Membrane Tranporter/Ion Channel Compound Library

[1] Souto-Padron, T., A.P. Lima, and O. Ribeiro Rde, Effects of dibucaine on the endocytic/exocytic pathways in Trypanosoma cruzi. Parasitol Res, 2006. 99(4): p. 317-20. [2] Elamin, B., Dibucaine inhibition of serum cholinesterase. J Biochem Mol Biol, 2003. 36(2): p. 149-53.

[1] http://www.ncbi.nlm.nih.gov/pubmed/16612626 [2] http://www.ncbi.nlm.nih.gov/pubmed/12689511

EOS XFZ-00021

3,3'-Diindolylmethane

1968/5/4

DIM;Arundine;HB 236

C17H14N2

246.3065

C1(CC2=CNC3=C2C=CC=C3)=CNC4=C1C=CC=C4

10 mM in DMSO

No Development Reported

Cancer

3,3'-Diindolylmethane is a strong, pure androgen receptor (AR) antagonist. IC50 & Target: Androgen receptor[1] In Vitro: 3,3'-Diindolylmethane (DIM) is a strong antagonist of androgen receptor (AR) function but exhibits less than obvious structural similarity to the endogenous AR ligand, dihydrotestosterone (DHT). 3,3'-Diindolylmethane is a major digestive product of indole-3-carbinol, a potential anticancer component of cruciferous vegetables. 3,3'-Diindolylmethane exhibits potent antiproliferative and antiandrogenic properties in androgen-dependent human prostate cancer cells. 3,3'-Diindolylmethane suppresses cell proliferation of LNCaP cells and inhibits DHT stimulation of DNA synthesis. Moreover, 3,3'-Diindolylmethane inhibits endogenous PSA transcription and reduced intracellular and secreted PSA protein levels induced by DHT in LNCaP cells. Also, 3,3'-Diindolylmethane inhibits, in a concentration-dependent manner, the DHT-induced expression of a prostate-specific antigen promoter-regulated reporter gene construct in transiently transfected LNCaP cells. Co-treatment with 50 μM 3,3'-Diindolylmethane partially inhibits the translocation of AR induced by DHT treatment and showed distribution of the AR to be both cytoplasmic and nuclear. Furthermore, 3,3'-Diindolylmethane treatment prevents the formation of AR foci in the nucleus. 3,3'-Diindolylmethane alone produces a predominantly cytoplasmic distribution of fluorescence[1]. In Vivo: Mice are randomized into two groups and are treated daily s.c. with either vehicle or 3,3'-Diindolylmethane (10 mg/kg) for 30 days. Tumor volume and the weight of mice are recorded once every 3 days using calipers. 3,3'-Diindolylmethane (DIM) treatment resulted in a marked inhibition of SNU-484 xenograft tumor growth. Notably, the body weight of mice from both groups did not significantly differ from the vehicle control following 30 days of drug exposure, suggesting that 3,3'-Diindolylmethane has no severe toxicity to the mice. Taken together, these findings demonstrate that 3,3'-Diindolylmethane administration significantly inhibited SNU-484 xenograft growthin vivo mediated by the inactivation of YAP[2].

Androgen Receptor

Others

Anti-cancer Compound Library; Clinical Compound Library; MCE online Bioactive Compound Library

[1] Prabodh K, et al. Activation of Checkpoint Kinase 2 by 3,3-Diindolylmethane Is Required for Causing G2/M Cell Cycle Arrest in Human Ovarian Cancer Cells. Mol Pharmacol 78:297-309, 2010 [2] Fan S, et al. DIM (3,3'-diindolylmethane) confers protection against ionizing radiation by a unique mechanism. Proc Natl Acad Sci U S A. 2013 Oct 14. [3] Poornima J, et al. Regulation of carbohydrate metabolism by indole-3-carbinol and its metabolite 3,3'-diindolylmethane in high-fat diet-induced C57BL/6J mice. Mol Cell Biochem. 2013 Sep 27. [4] Li XJ, et al. 3,3'-Diindolylmethane suppresses the growth of gastric cancer cells via activation of the Hippo signaling pathway. Oncol Rep. 2013 Nov;30(5):2419-26. [5] Kandala PK, et al. Blocking epidermal growth factor receptor activation by 3,3'-diindolylmethane suppresses ovarian tumor growth in vitro and in vivo. J Pharmacol Exp Ther. 2012 Apr;341(1):24-32. [6] Leibelt DA, et al. Evaluation of chronic dietary exposure to indole-3-carbinol and absorption-enhanced 3,3'-diindolylmethane in sprague-dawley rats. Toxicol Sci. 2003 Jul;74(1):10-21.

[1] http://molpharm.aspetjournals.org/content/78/2/297.full.pdf [2] http://www.ncbi.nlm.nih.gov/pubmed/24127581 [3] http://www.ncbi.nlm.nih.gov/pubmed/24072613 [4] http://www.ncbi.nlm.nih.gov/pubmed/24008339 [5] http://www.ncbi.nlm.nih.gov/pubmed/22205686 [6] http://www.ncbi.nlm.nih.gov/pubmed/12730619

EOS XFZ-00022

Quinacrine (dihydrochloride)

1969/5/6

Mepacrine dihydrochloride;SN-390

C23H32Cl3N3O

472.8787

CC(NC1=C(C=C(OC)C=C2)C2=NC3=CC(Cl)=CC=C31)CCCN(CC)CC.Cl.Cl

DMSO: ≥ 44 mg/mL

Phase 2 Clinical

Cancer

Quinacrine is a fluorescent probe for the conformational transitions of the cholinergic receptor protein. Quinacrine shows activity in the low μM range with a mean IC50 of 2.30 μM In the patient AML cells. IC50 value: 2.30 μM (for AML cells) Target: in vitro: Quinacrine is a fluorescent probe for the conformational transitions of the cholinergic receptor protein in its membrane-bound state.[1] In the patient AML samples, Quinacrine showed activity in the low μM range with a mean IC50 of 2.30 μM, statistically significantly lower than that of normal PBMCs; 3.54 μM (P=0.0327; Student's t-test). Samples from patients with chronic lymphocytic, acute myeloid and lymphocytic leukemias as well as peripheral blood mononuclear cells (PBMC) were tested in response to 1266 compounds from the LOPAC1280 library. 25 compounds were defined as hits with activity in all leukemia subgroups (<50% cell survival compared with control) at 10 μM drug concentration. Only Quinacrine showed concurrent high activity in all leukemia subgroups and low activity in normal PBMCs and was, therefore, selected for further preclinical evaluation. Quinacrine also induced early inhibition of both DNA and protein synthesis. Quinacrine have repositioning potential for treatment of acute myeloid leukemia by targeting of ribosomal biogenesis.[2]

Autophagy; Phospholipase

Autophagy; Metabolic Enzyme/Protease

Anti-cancer Compound Library; Autophagy Compound Library; Clinical Compound Library; MCE online Bioactive Compound Library; Metabolism/Protease Compound Library

[1] Grünhagen HH, et al. Studies on the electrogenic action of acetylcholine with Torpedo marmorata electric organ. IV. Quinacrine: a fluorescent probe for the conformational transitions of the cholinergic receptor protein in its membrane-bound state. J Mol Biol. 1976 Sep 25;106(3):497-516. [2] Eriksson A, et al. Drug screen in patient cells suggests quinacrine to be repositioned for treatment of acute myeloid leukemia. Blood Cancer J. 2015 Apr 17;5:e307. 

[1] http://www.ncbi.nlm.nih.gov/pubmed/978733 [2] http://www.ncbi.nlm.nih.gov/pubmed/25885427

EOS XFZ-00023

Loxapine

1977/10/2

C18H18ClN3O

327.808

CN1CCN(C2=NC3=CC=CC=C3OC4=CC=C(Cl)C=C24)CC1

10 mM in DMSO

Launched

Neurological Disease

Loxapine Succinate is a D2DR and D4DR inhibitor, serotonergic receptor antagonist and also a dibenzoxazepine anti-psychotic agent. IC50 value: Target: D2DR/D4DR; 5-HT receptor in vitro: In the presence of Loxapine, [3H]ketanserin binds to 5-HT2 receptor in Frontal cortex of brain in human and bovine with ki value of 6.2 nM and 6.6 nM, respectively. Loxapine has the rank order of potency for the various receptors appears to be as follows:5-HT2≥D4>>>D1>D2 in comparing competition experiments involving the human membranes [1]. Loxapine 0.2 μM, 2 μM and 20 μM reduces IL-1beta secretion by LPS-activated mixed glia cultures after 1 and 3 days of exposure. Loxapine in concentrations of 0.2 μM, 2 μM and 20 μM reduces IL-2 secretion in mixed glia cultures after 1 and 3 days of exposure, and additionally Loxapine decreases IL-1beta and IL-2 secretion in LPS-induced microglia cultures in concentrations of 2 μM, 10 μM and 20 μM [2]. in vivo: Loxapine (5 mg/kg) induces a very significant reduction (more than 50%) of serotonin (S2) receptor density after 4 weeks or 10 weeks of daily injection in the rat. Loxapine (5 mg/kg) does not change dopamine receptor density but greatly reduces serotonin receptor density by 47% in the brain of rats [3].

5-HT Receptor

GPCR/G protein; Neuronal Signaling

FDA-approved_Drug_Library; GPCR/G protein Compound Library; MCE online Bioactive Compound Library; Neuronal Signaling Compound Library

[1] Singh AN, et al. A neurochemical basis for the antipsychotic activity of loxapine: interactions with dopamine D1, D2, D4 and serotonin 5-HT2 receptor subtypes. J Psychiatry Neurosci. 1996 Jan;21(1):29-35. [2] Labuzek K, et al. Chlorpromazine and loxapine reduce interleukin-1beta and interleukin-2 release by rat mixed glial and microglial cell cultures. Eur Neuropsychopharmacol. 2005 Jan;15(1):23-30. [3] Lee T, et al. Loxapine and clozapine decrease serotonin (S2) but do not elevate dopamine (D2) receptor numbers in the rat brain. Psychiatry Res. 1984 Aug;12(4):277-85. [4] Kalkman HO, et al. Clozapine inhibits catalepsy induced by olanzapine and loxapine, but prolongs catalepsy induced by SCH 23390 in rats. Naunyn Schmiedebergs Arch Pharmacol. 1997 Mar;355(3):361-4.

[1] http://www.ncbi.nlm.nih.gov/pubmed/8580115 [2] http://www.ncbi.nlm.nih.gov/pubmed/15572270 [3] http://www.ncbi.nlm.nih.gov/pubmed/6239298 [4] http://www.ncbi.nlm.nih.gov/pubmed/9089667

EOS XFZ-00024

4-Aminoantipyrine

1983/7/8

Ampyrone

C11H13N3O

203.2404

O=C1N(C2=CC=CC=C2)N(C)C(C)=C1N

10 mM in DMSO

Launched

Others

4-Aminoantipyrine is a reagent for glucose determination in the presence of peroxidase and phenol.

Others

FDA-approved_Drug_Library; MCE online Bioactive Compound Library

EOS XFZ-00025

Phenindione

1983/12/5

Rectadione

C15H10O2

222.2387

O=C1C(C2=CC=CC=C2)C(C3=C1C=CC=C3)=O

10 mM in DMSO

Launched

Cardiovascular Disease

Phenindione is an anticoagulant which functions as a Vitamin K antagonist. Target: Others Phenindione(Rectadione) is an anticoagulant which functions as a Vitamin K antagonist. A lymphocyte transformation test showed proliferation of T-cells from the hypersensitive patient, but not from four controls on exposure to phenindione in vitro. Drug-specific T-cell clones were generated and characterized in terms of their phenotype, functionality, and mechanism of antigen presentation. Forty-three human leukocyte antigen class II restricted CD4+ αβ T-cell clones were identified. T-cell activation resulted in the secretion of interferon-γ and interleukin-5 [1].

Others

FDA-approved_Drug_Library; MCE online Bioactive Compound Library

[1] Naisbitt, D.J., et al., Characterization of the T-cell response in a patient with phenindione hypersensitivity. Journal of Pharmacology and Experimental Therapeutics, 2005. 313(3): p. 1058-1065.

[1] http://jpet.aspetjournals.org/content/313/3/1058.short

EOS XFZ-00026

Salicyl alcohol

1990/1/7

2-Hydroxybenzyl alcohol;Saligenin

C7H8O2

124.1372

OCC1=CC=CC=C1O

10 mM in DMSO

Launched

Others

Salicyl alcohol is an intermediate for medicine, perfume, pesticide.

Others

FDA-approved_Drug_Library; MCE online Bioactive Compound Library

EOS XFZ-00027

Benzocaine

1994/9/7

C9H11NO2

165.1891

O=C(OCC)C1=CC=C(N)C=C1

10 mM in DMSO

No Development Reported

Others

benzocaine is a common receptor with all other local anesthetics (LAs) in the voltage-gated Na+ channel. exerts an indirect action on the membrane permeability to calcium. key steps of the Ca-ATPase enzymatic cycle. In vitro: benzocaine is effective at blocking mu1-N1584A current than the wild-type current, while they are less potent at blocking mu1-F1579A current.[1] Benzocaine also interfered with the calcium transport capability by decreasing the maximal uptake (IC50 40.3 mM) without modification of the calcium affinity for the ATPase. It inhibited the phosphorylation of the enzyme, and at high benzocaine concentration. [2]

Sodium Channel

Membrane Transporter/Ion Channel

Clinical Compound Library; MCE online Bioactive Compound Library; Membrane Tranporter/Ion Channel Compound Library

[1] Wang GK et al. A common local anesthetic receptor for benzocaine and etidocaine in voltage-gated mu1 Na+ channels. Pflugers Arch. 1998 Jan;435(2):293-302. [2] Di Croce D et al. Drug action of benzocaine on the sarcoplasmic reticulum Ca-ATPase from fast-twitch skeletal muscle. Naunyn Schmiedebergs Arch Pharmacol. 2015 Nov;388(11):1163-70.

[1] http://www.ncbi.nlm.nih.gov/pubmed/9382945 [2] http://www.ncbi.nlm.nih.gov/pubmed/26173386

EOS XFZ-00028

Asparagusic acid

2224/2/4

C4H6O2S2

150.2192

O=C(O)C1CSSC1

DMSO: ≥ 46 mg/mL

Discovery

Others

Asparagusic acid (1,2-dithiolane-4-carboxylic acid) is unique to asparagus. The compound is responsible for the odorous urine excreted after eating asparagus. Its derivatives ihydroasparagusic acid have anti-inflammatory effect.

Others

Clinical Compound Library; MCE online Bioactive Compound Library

[1] Mitchell SC et al. Asparagusic acid. Phytochemistry. 2014 Jan;97:5-10.

[1] https://www.ncbi.nlm.nih.gov/pubmed/24099657

EOS XFZ-00029

Oxymetazoline (hydrochloride)

2315/2/8

C16H25ClN2O

296.8355

OC1=C(C(C)(C)C)C=C(C)C(CC2=NCCN2)=C1C.Cl

DMSO: ≥ 39 mg/mL

Launched

Neurological Disease

Oxymetazoline Hydrochloride is a selective alpha-1 agonist and partial alpha-2 agonist topical decongestant. Target: Alpha Adrenergic Receptor Oxymetazoline is a selective alpha-1 agonist and partial alpha-2 agonist topical decongestant, used in the form of Oxymetazoline hydrochloride. It was developed from xylometazoline at E. Merck Darmstadt by Fruhstorfer in 1961. Oxymetazoline is generally available as a nasal spray. Oxymetazoline is a sympathomimetic that selectively agonizes α1 and partially α2 adrenergic receptors. Since vascular beds widely express α1 receptors, the action of oxymetazoline results in vasoconstriction. In addition, the local application of the drug also results in vasoconstriction due to its action on endothelial postsynaptic α2 receptors; systemic application of α2 agonists, in contrast, causes vasodilation because of centrally-mediated inhibition of sympathetic tone via presynaptic α2 receptors. Vasoconstriction of vessels results in relief of nasal congestion in two ways: First, it increases the diameter of the airway lumen; second, it reduces fluid exudation from postcapillary venules. It can reduce Nasal Airway Resistance (NAR) up to 35.7% and Nasal mucosal blood flow up to 50% [1].

Adrenergic Receptor

GPCR/G protein

FDA-approved_Drug_Library; GPCR/G protein Compound Library; MCE online Bioactive Compound Library

[1] Widdicombe, J., Microvascular anatomy of the nose. Allergy, 1997. 52(40 Suppl): p. 7-11. [2] http://en.wikipedia.org/wiki/Oxymetazoline

[1] http://www.ncbi.nlm.nih.gov/pubmed/9353554 [2] http://en.wikipedia.org/wiki/Oxymetazoline

EOS XFZ-00030

Terpin (hydrate)

2451/1/6

Terpin monohydrate;cis-Terpin hydrate

C10H22O3

190.2799

O[C@]1(C)CC[C@H](C(C)(C)O)CC1.O

H2O: ≥ 1.9 mg/mL

Launched

Inflammation/Immunology

Terpin hydrate is an expectorant, commonly used to loosen mucus in patients presenting with acute or chronic bronchitis, and related conditions.

Others

FDA-approved_Drug_Library; MCE online Bioactive Compound Library

EOS XFZ-00031

FH1

2719/5/3

NSC 12407;BRD-K4477;FH 1;NSC12407;BRDK4477

C17H18N2O2

282.337

CC(NC1=CC=C(CC2=CC=C(NC(C)=O)C=C2)C=C1)=O

DMSO: 13 mg/mL

No Development Reported

Others

FH1(BRDK4477) is a small molecule that can enhance the functions of cultured hepatocytes. IC50 value: Target: In vitro: FH1(BRD-K4477) enhances hepatocyte functions, and promotes the maturation of well-differentiated cultures of iHeps, which potentially alleviates a major obstacle to the use of iPS cells as a renewable source of functional human hepatocytes.

Others

Clinical Compound Library; MCE online Bioactive Compound Library

[1] Shan J, et al. Identification of small molecules for human hepatocyte expansion and iPS differentiation. Nat Chem Biol. 2013 Aug;9(8):514-20.

[1] http://www.ncbi.nlm.nih.gov/pubmed/23728495

EOS XFZ-00032

Doxifluridine

3094/9/5

Ro 21-9738;5-Fluoro-5'-deoxyuridine;5'-DFUR

C9H11FN2O5

246.1924

C[C@@H]1[C@H]([C@H]([C@H](N2C(NC(C(F)=C2)=O)=O)O1)O)O

10 mM in DMSO

Launched

Cancer

Doxifluridine(Ro 21-9738; 5'-DFUR) is a thymidine phosphorylase activator for PC9-DPE2 cells with IC50 of 0.62 μM. IC50 value: 0.62 μM(PC9-DPE2 cell). Target: Nucleoside antimetabolite/analog Doxifluridine is a fluoropyrimidine derivative and oral prodrug of the antineoplastic agent 5-fluorouracil (5-FU) with antitumor activity. Doxifluridine, designed to circumvent the rapid degradation of 5-FU by dihydropyrimidine dehydrogenase in the gut wall, is converted into 5-FU in the presence of pyrimidine nucleoside phosphorylase. 5-FU interferes with DNA synthesis and subsequent cell division by reducing normal thymidine production and interferes with RNA transcription by competing with uridine triphosphate for incorporation into the RNA strand. in vitro: 5'-DFUR's metabolic product(N3-Me-5'-dFUR) was found to be non-toxic in all the cell growth experiments performed. The absence of cytotoxicity could be explained by the observation that the metabolite was not recognized as a substrate by thymidine phosphorilase, the enzyme responsible for 5-fluorouracil (5-FU) release from doxifluridine, as ascertained by high-performance liquid chromatography/ultraviolet (HPLC-UV) analysis of the incubation mixture[1]. in vivo: Administration of 200 mg of Furtulon to 23 beagle dogs, the plasma concentrations of doxifluridine, 5-FU, and 5-FUrd were measured simultaneously, using LC-MS/MS. The parent-metabolite compartment model with first-order absorption and Michaelis-Menten kinetics described the pharmacokinetics of doxifluridine, 5-FU, and 5-FUrd. Michaelis-Menten kinetics sufficiently explained the generation and elimination processes of 5-FU and 5-FUrd[2]. Clinical trial: A phase II study of doxifluridine and docetaxel combination chemotherapy for advanced or recurrent gastric cancer was reported in 2009[3].

Nucleoside antimetabolite/analog

Cell Cycle/DNA Damage

Anti-cancer Compound Library; Cell Cycle/DNA Damage Compound Library; FDA-approved_Drug_Library; MCE online Bioactive Compound Library

[1] Dipartimento di Chimica, Università degli Studi della Basilicata, Potenza, In vitro toxicity of N3-methyl-5'-deoxy-5-fluorouridine, a novel metabolite of doxifluridine: a bioanalytical investigation. J Pharm Biomed Anal. 1998 May;17(1):11-6. [2] Baek IH, Lee BY, Kim MS, Pharmacokinetic analysis of doxifluridine and its metabolites, 5-fluorouracil and 5-fluorouridine, after oral administration in beagle dogs. Eur J Drug Metab Pharmacokinet. 2013 Apr 7. [3] Yoshikawa T, Tsuburaya A, Shimada K, A phase II study of doxifluridine and docetaxel combination chemotherapy for advanced or recurrent gastric cancer. Gastric Cancer. 2009;12(4):212-8.

[1] http://www.ncbi.nlm.nih.gov/pubmed/9608421 [2] http://www.ncbi.nlm.nih.gov/pubmed/23564503 [3] http://www.ncbi.nlm.nih.gov/pubmed/20047126

EOS XFZ-00033

Pristinamycin IA

3131/3/1

Mikamycin B;Mikamycin IA

C45H54N8O10

866.9579

O=C(C(N(C(C(CCC1)N1C(C(NC2=O)CC)=O)=O)C)CC3=CC=C(N(C)C)C=C3)N(CCC4=O)C(C4)C(NC(C5=CC=CC=C5)C(OC(C2NC(C(N=CC=C6)=C6O)=O)C)=O)=O

DMSO: ≥ 28 mg/mL

No Development Reported

Others

Pristinamycin IA is a cyclo-peptidic macrolactone antibiotic belonging to the streptogramin family, a substrate for the P-glycoprotein. In vitro: Pristinamycin IA specifically inhibits the efflux of the P-glycoprotein substrate [3H]vinblastine, thus increasing the cellular accumulation of the drug. Pristinamycin IA also reduces by 70% the basolateral to apical secretion of [3H]vinblastine across Caco-2 cell monolayers. The cellular accumulation of [14C]pristinamycin IA is very low and is increased by P-glycoprotein inhibitors (verapamil, chlorpromazine and reserpine). The basolateral to apical transport of [14C]pristinamycin IA is 100-fold higher than apical to basolateral passage. [1]

Others

[1] Phung-Ba V et al. Interaction of pristinamycin IA with P-glycoprotein in human intestinal epithelial cells. Eur J Pharmacol. 1995 Jan 16;288(2):187-92.

[1] http://www.ncbi.nlm.nih.gov/pubmed/ 7720780

EOS XFZ-00034

Naftidrofuryl (oxalate)

3200/6/4

Nafronyl oxalate salt

C26H35NO7

473.5586

O=C(OCCN(CC)CC)C(CC1=C2C=CC=CC2=CC=C1)CC3OCCC3.O=C(O)C(O)=O

DMSO: 10 mg/mL

Launched

Cardiovascular Disease

Naftidrofuryl is a drug used in the management of peripheral and cerebral vascular disorders as a vasodilator, enhance cellular oxidative capacity, and may also be a 5-HT2 receptor antagonist. Target: 5-HT2 receptor Naftidrofuryl may be effective for relieving the pain of muscle cramps.[1] Naftidrofuryl oxalate is the only vasoactive drug for peripheral arterial disease (PAD) which is likely to be cost-effective.[2] Naftidrofuryl oxalate is ranked first for both maximum walking distance (MWD) and pain-free walking distance (PFWD) (probability of 0·947 and 0·987, respectively, of being the best treatment) followed by cilostazol and pentoxifylline. Naftidrofuryl oxalate is effective treatments for claudication, Naftidrofuryl oxalate is likely to be the most effective, with minimal serious adverse events.[3]

5-HT Receptor

GPCR/G protein; Neuronal Signaling

FDA-approved_Drug_Library; GPCR/G protein Compound Library; MCE online Bioactive Compound Library; Neuronal Signaling Compound Library

[1] Naftidrofuryl [2] Meng Y, et al. Cost-effectiveness of cilostazol, naftidrofuryl oxalate, and pentoxifylline for the treatment of intermittent claudication in people with peripheral arterial disease. Angiology. 2014 Mar;65(3):190-197. [3] Stevens JW, et al. Systematic review of the efficacy of cilostazol, naftidrofuryl oxalate and pentoxifylline for the treatment of intermittent claudication. Br J Surg. 2012 Dec;99(12):1630-1638.

[1] https://en.wikipedia.org/wiki/Naftidrofuryl [2] http://www.ncbi.nlm.nih.gov/pubmed/23378195 [3] http://www.ncbi.nlm.nih.gov/pubmed/23034699

EOS XFZ-00035

6-CFDA

3348/3/6

6-Carboxyfluorescein diacetate

C25H16O9

460.3891

CC(OC1=CC=C(C2(O3)C4=CC(C(O)=O)=CC=C4C3=O)C(OC5=C2C=CC(OC(C)=O)=C5)=C1)=O

DMSO: ≥ 44 mg/mL; Protect from light

No Development Reported

Others

6-CFDA is fluorescent polyanionic probe, and its derivatives such as 2′,7′-bis (2-carboxyethyl)-5(6)-carboxyfluorescein are used to measure changes in intracellular pH (pHi) and processes such as dendrimer aggregation and absorption.

Biochemical assay reagents

Biochemical Reagent

[1] Babcock DF. Examination of the intracellular ionic environment and of ionophore action by point measurements employing the fluorescein chromophore. J Biol Chem. 1983 May 25;258(10):6380-9. [2] Graber ML, et al. Characteristics of fluoroprobes for measuring intracellular pH. Anal Biochem. 1986 Jul;156(1):202-12. [3] Bonizzoni M, et al. PAMAM dendrimer-induced aggregation of 5(6)-carboxyfluorescein. J Org Chem. 2012 Feb 3;77(3):1258-66.

[1] http://www.ncbi.nlm.nih.gov/pubmed/6853488 [2] http://www.ncbi.nlm.nih.gov/pubmed/3740410 [3] http://www.ncbi.nlm.nih.gov/pubmed/22145833

EOS XFZ-00036

Flunisolide

3385/3/3

C24H31FO6

434.4977

C[C@@]12[C@@]3(C(CO)=O)[C@@](OC(C)(O3)C)([H])C[C@@]1([H])[C@]4([H])C[C@H](F)C5=CC(C=C[C@]5(C)[C@@]4([H])[C@@H](O)C2)=O

10 mM in DMSO

Launched

Inflammation/Immunology

Flunisolide is a corticosteroid often used to treat allergic rhinitis.The principal mechanism of action of Flunisolide is to activate glucocorticoid receptors, meaning it has an anti-inflammatory action.

Glucocorticoid Receptor

GPCR/G protein

EOS XFZ-00037

DTT

3483/12/3

DL-Dithiothreitol;Cleland’s reagent

C4H10O2S2

154.251

O[C@H]([C@@H](O)CS)CS

10 mM in H2O

No Development Reported

Others

Dithiothreitol (DTT) is the common name for a small-molecule redox reagent known as Cleland's reagent; as a reducing or "deprotecting" agent for thiolated DNA.

Biochemical assay reagents

Biochemical Reagent

Clinical Compound Library; MCE online Bioactive Compound Library

[1] Dithiothreitol, From Wikipedia

[1] http://en.wikipedia.org/wiki/Dithiothreitol

EOS XFZ-00038

Zebularine

3690/10/6

NSC309132;4-Deoxyuridine

C9H12N2O5

228.202

O=C1N=CC=CN1[C@H]2[C@@H]([C@@H]([C@@H](CO)O2)O)O

DMSO: ≥ 29 mg/mL

No Development Reported

Cancer

Zebularine(NSC309132; 4-Deoxyuridine) is a DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases, also inhibits cytidinedeaminase with Ki of 2 μM. IC50 value: Target: DNA methyltransferase in vitro: Zebularine is shown to form a tight, covalent complex with bacterial methyltransferases [1]. Zebularine is a cytidine analogue containing a 2-(1H)-pyrimidinone ring, originally synthesized as a cytidine deaminase inhibitor [2]. In N. crassa, zebularine inhibits DNA methylation and reactivates a gene previously silenced by methylation. Zebularine is a global inhibitor of DNA methylation, similar to 5-Aza-CR, rather than a selective inhibitor. Zebularine induces the myogenic phenotype in 10T1/2 cells, which is a phenomenon unique to DNA methylation inhibitors. Zebularine reactivates a silenced p16 gene and demethylates its promoter region in T24 bladder carcinoma cells. Zebularine is only slightly cytotoxic to T24 cells [3]. Zebularine is preferentially incorporated into DNA and exhibits greater cell growth inhibition and gene expression in cancer cell lines compared to normal fibroblasts. In addition, zebularine preferentially depletes DNA methyltransferase 1 (DNMT1) and induces expression of cancer-related antigen genes in cancer cells relative to normal fibroblasts [4]. in vivo: Zebularine is only slightly cytotoxic to tumor-bearing mice (average maximal weight change in mice treated with 1000 mg/kg zebularine = 11% [95% CI = 4% to 19%]). Compared with those in control mice, tumor volumes are statistically significantly reduced in mice treated with high-dose zebularine administered by intraperitoneal injection or by oral gavage [3].

Autophagy; DNA Methyltransferase

Autophagy; Epigenetics

Anti-cancer Compound Library; Autophagy Compound Library; Clinical Compound Library; Epigenetics Compound Library; MCE online Bioactive Compound Library

[1] Zhou L, et al. Zebularine: a novel DNA methylation inhibitor that forms a covalent complex with DNA methyltransferases. J Mol Biol, 2002, 321(4), 591-599. [2] Lemaire M, et al. Inhibition of cytidine deaminase by zebularine enhances the antineoplastic action of 5-aza-2'-deoxycytidine. Cancer Chemother Pharmacol, 2009, 63(3), 411-416. [3] Cheng JC, et al. Inhibition of DNA methylation and reactivation of silenced genes by zebularine. J Natl Cancer Inst, 2003, 95(5), 399-409. [4] Cheng JC, et al. Preferential response of cancer cells to zebularine. Cancer Cell, 2004, 6(2), 151-158.

[1] http://www.ncbi.nlm.nih.gov/pubmed/12206775 [2] http://www.ncbi.nlm.nih.gov/pubmed/18398609 [3] http://www.ncbi.nlm.nih.gov/pubmed/12618505 [4] http://www.ncbi.nlm.nih.gov/pubmed/15324698

EOS XFZ-00039

Dacarbazine

4342/3/4

Imidazole Carboxamide

C6H10N6O

182.1832

O=C(C1=C(/N=N/N(C)C)NC=N1)N

DMSO: ＜ 9.4 mg/mL

Launched

Cancer

Dacarbazine(DTIC-Dome; DTIC) is an antineoplastic agent. It has significant activity against melanomas. Target: Nucleoside antimetabolite/analog Approved: May 1975 Dacarbazine (DTIC) is the only single-agent approved by the Food and Drug Administration for treating metastatic melanoma. With DTIC as single agent, an approximately 20% objective response rate can be achieved with median response duration of 5 to 6 months and complete response rates of 5% [1]. Dacarbazine (DTIC) has activity in advanced previously untreated pancreatic islet cell tumors [2]. In the intent-to-treat population, median survival time was 7.7 months for patients treated with temozolomide and 6.4 months for those treated with DTIC (hazards ratio, 1.18; 95% confidence interval [CI], 0.92 to 1.52). Median PFS time was significantly longer in the temozolomide-treated group (1.9 months) than in the DTIC-treated group (1.5 months) (P = .012; hazards ratio, 1.37; 95% CI, 1.07 to 1.75) [3].

Nucleoside antimetabolite/analog

Cell Cycle/DNA Damage

Anti-cancer Compound Library; Cell Cycle/DNA Damage Compound Library; FDA-approved_Drug_Library; MCE online Bioactive Compound Library

[1] Serrone, L., et al., Dacarbazine-based chemotherapy for metastatic melanoma: thirty-year experience overview. J Exp Clin Cancer Res, 2000. 19(1): p. 21-34. [2] Ramanathan, R.K., et al., Phase II trial of dacarbazine (DTIC) in advanced pancreatic islet cell carcinoma. Study of the Eastern Cooperative Oncology Group-E6282. Ann Oncol, 2001. 12(8): p. 1139-43. [3] Middleton, M.R., et al., Randomized phase III study of temozolomide versus dacarbazine in the treatment of patients with advanced metastatic malignant melanoma. J Clin Oncol, 2000. 18(1): p. 158-66.

[1] http://www.ncbi.nlm.nih.gov/pubmed/10840932 [2] http://www.ncbi.nlm.nih.gov/pubmed/11583197 [3] http://www.ncbi.nlm.nih.gov/pubmed/10623706

EOS XFZ-00040

Ajmaline

4360/12/7

Cardiorythmine;(+)-Ajmaline

C20H26N2O2

326.4326

CN1C2=CC=CC=C2[C@@]34[C@]1([H])[C@@](CC5[C@H](CC)[C@H]6O)([H])N6[C@]([H])(C5[C@H]4O)C3

10 mM in DMSO

Launched

Cardiovascular Disease

Ajmaline is an alkaloid that is class Ia antiarrhythmic agent.

Others

FDA-approved_Drug_Library; MCE online Bioactive Compound Library

EOS XFZ-00041

Theaflavin

4670/5/7

C29H24O12

564.4937

O=C1C(O)=CC([C@@H]2[C@H](O)CC3=C(O)C=C(O)C=C3O2)=CC4=C([C@@H]5[C@H](O)CC6=C(O)C=C(O)C=C6O5)C=C(O)C(O)=C41

10 mM in H2O

No Development Reported

Infection

Theaflavin is a suitable natural inhibitor against influenza A (H1N1) neuraminidase. IC50 & Target: Influenza A (H1N1) virus[1] InVitro: Theaflavin, found in green tea, is observed to inhibit H1N1 NA proteins strongly supported by lowest docking energy. Theaflavin is a plant product traditionally used for treatment of influenza infection. Green tea is particularly rich in polyphenolic compounds like Theaflavin. Theaflavin derivatives have shown pronounced antiviral activity. Theaflavin is found to interact with the amino acid residues like Arg118, Asp151, Asp 152, Arg193, Asp199, Asn344, and Arg430 of NA by forming hydrogen bonds[1].

Influenza Virus

Anti-infection

[1] Sahoo M, et al. Identification of Suitable Natural Inhibitor against Influenza A (H1N1) Neuraminidase Protein by Molecular Docking. Genomics Inform. 2016 Sep;14(3):96-103.

[1] https://www.ncbi.nlm.nih.gov/pubmed/27729839

EOS XFZ-00042

Fenspiride (Hydrochloride)

5053/8/7

C15H21ClN2O2

296.7924

O=C1OC2(CCN(CCC3=CC=CC=C3)CC2)CN1.[H]Cl

10 mM in DMSO

Suspended

Inflammation/Immunology

Fenspiride Hcl is an α adrenergic and H1 histamine receptor antagonist. IC50 value: Target: Adrenergic receptor; H1 receptor Fenspiride hydrochloride is a bronchodilator with anti-inflammatory properties. Fenspiride hydrochloride inhibits mucus secretion and reduces the release of tachykinins at a prejunctional level. Fenspiride hydrochloride also may be an antagonist at α adrenergic and H1 histamine receptors.

Adrenergic Receptor; Histamine Receptor

GPCR/G protein

Clinical Compound Library; GPCR/G protein Compound Library; MCE online Bioactive Compound Library

[1] Khawaja AM, Liu YC, Rogers DF. et al.Effect of fenspiride, a non-steroidal antiinflammatory agent, on neurogenic mucus secretion in ferret trachea in vitro. Pulm Pharmacol Ther. 1999;12(6):363-8. [2] Zielnik-Jurkiewicz B, Jurkiewicz D. et al. Usefulness of fenspiride in the treatment of acute otitis media in children. Pol Merkur Lekarski. 2005 Jun;18(108):624-8. [3] Bee D, Laude EA, Emery CJ, Howard P. Effect of fenspiride on pulmonary function in the rat and guinea pig. Clin Sci (Lond). 1995 Mar;88(3):325-30. [4] Fenspiride [5] Lebedenko AA, Mal'tsev SV. .[The efficacy of application of fenspiride (erespal) for the treatment of exacerbation of bronchial asthma in children.] Vestn Otorinolaringol. 2011;(4):66-67.

[1] http://www.ncbi.nlm.nih.gov/pubmed/10587477 [2] http://www.ncbi.nlm.nih.gov/pubmed/16124370 [3] http://www.ncbi.nlm.nih.gov/pubmed/7736702 [4] http://en.wikipedia.org/wiki/Fenspiride [5] http://www.ncbi.nlm.nih.gov/pubmed/21983674

EOS XFZ-00043

Mexiletine (hydrochloride)

5370/1/4

C11H18ClNO

215.7197

CC(N)COC1=C(C)C=CC=C1C.[H]Cl

DMSO: ≥ 41 mg/mL

Launched

Cardiovascular Disease

Mexiletine hydrochloride is a non-selective voltage-gated sodium channel blocker; Class IB anti-arrhythmic compound.

Sodium Channel

Membrane Transporter/Ion Channel

FDA-approved_Drug_Library; MCE online Bioactive Compound Library; Membrane Tranporter/Ion Channel Compound Library

[1] Desaphy JF, et al. Effect of mexiletine on sea anemone toxin-induced non-inactivating sodium channels of rat skeletal muscle: a model of sodium channel myotonia. Neuromuscul Disord. 1999 May;9(3):182-9. [2] Mori K, et al. Inhibitory effects of class I and IV antiarrhythmic drugs on the Na+-activated K+ channel current in guinea pig ventricular cells. Naunyn Schmiedebergs Arch Pharmacol. 1998 Dec;358(6):641-8.

[1] http://www.ncbi.nlm.nih.gov/pubmed/10382914 [2] http://www.ncbi.nlm.nih.gov/pubmed/9879723

EOS XFZ-00044

Cynaroside

5373/11/5

Luteolin 7-glucoside;Luteolin 7-O-β-D-glucoside

C21H20O11

448.3769

O=C(C=C(C1=CC(O)=C(O)C=C1)OC2=CC(O[C@@H]([C@@H]([C@@H](O)[C@@H]3O)O)O[C@@H]3CO)=C4)C2=C4O

DMSO: ≥ 35 mg/mL

No Development Reported

Others

Cynaroside is a flavone, a flavonoid-like chemical compound. It is a 7-O-glucoside of luteolin.

Others

Clinical Compound Library; MCE online Bioactive Compound Library; Natural Product Library

EOS XFZ-00045

5-Aminolevulinic acid (hydrochloride)

5451/9/2

ALA;5-ALA

C5H10ClNO3

167.5908

O=C(O)CCC(CN)=O.[H]Cl

10 mM in DMSO

Launched

Metabolic Disease

5-Aminolevulinic acid HCl is an intermediate in heme biosynthesis in the body and the universal precursor of tetrapyrroles. Target: Others 5-Aminolevulinic acid is a non-fluorescent prodrug that leads to intracellular accumulation of fluorescent porphyrins in malignant gliomas-a finding that is under investigation for intraoperative identification and resection of these tumours. Median follow-up was 35.4 months (95% CI 1.0-56.7). Contrast-enhancing tumour was resected completely in 90 (65%) of 139 patients assigned 5-aminolevulinic acid compared with 47 (36%) of 131 assigned white light (difference between groups 29% [95% CI 17-40], p<0.0001). Patients allocated 5-aminolevulinic acid had higher 6-month progression free survival than did those allocated white light (41.0% [32.8-49.2] vs 21.1% [14.0-28.2]; difference between groups 19.9% [9.1-30.7], p=0.0003, Z test) [1]. 5-ALA alone proved to be insufficient in attaining gross total resection without the danger of incurring postoperative neurological deterioration. Furthermore, in the case of functional grade III gliomas, iMRI in combination with functional neuronavigation was significantly superior to the 5-ALA resection technique [2].

Autophagy

Autophagy Compound Library; FDA-approved_Drug_Library; MCE online Bioactive Compound Library; Natural Product Library

[1] Stummer, W., et al., Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol, 2006. 7(5): p. 392-401. [2] Eyupoglu, I.Y., et al., Improving the extent of malignant glioma resection by dual intraoperative visualization approach. PLoS One, 2012. 7(9): p. e44885.

[1] http://www.ncbi.nlm.nih.gov/pubmed/16648043 [2] http://www.ncbi.nlm.nih.gov/pubmed/23049761

EOS XFZ-00046

Beclometasone dipropionate

5534/9/8

C28H37ClO7

521.0422

C[C@@]12[C@](C[C@H](C)[C@]2(OC(CC)=O)C(COC(CC)=O)=O)([H])[C@]3([H])CCC4=CC(C=C[C@]4(C)[C@@]3(Cl)[C@@H](O)C1)=O

10 mM in DMSO

Launched

Inflammation/Immunology

Beclometasone dipropionate is a potent glucocorticoid agonist; it is a prodrug of the free form, beclometasone. IC50 Value: 0.2 nM (Inhibiting thymidine incorporation) [1] Target: glucocorticoid receptor in vitro: Cortisol and beclomethasone dipropionate were more potent than salbutamol in inhibiting thymidine incorporation with IC50 values of 5 nM and 0.2 nM respectively. Cortisol 100 nM led to a 16.6 +/- 6.5% reduction and beclomethasone dipropionate 3 nM led to a 17.8 +/- 5.8% reduction in cell number [1]. in vivo: Controlled trials involving 497 adults and children demonstrated similar clinical efficacy between nebulized BDP and either nebulized fluticasone propionate or nebulized budesonide. Meta-analyses show that BDP, like other inhaled corticosteroids, has no major influence on patient height, urinary cortisol concentration, or bone metabolism [2]. Beclometasone dipropionate (BDP) 800 microgday(-1) suspension for nebulization and budesonide (BUD) 750 microg day(-1) given by nebulization in a twice-daily regimen, and when used in addition to the usual maintenance therapy, resulted in comparable clinical efficacy across all parameters [3]. Clinical trial: Efficacy and Tolerability of Beclometasone/Formoterol Single Inhaler in Patients With Moderate to Severe Persistent Asthma. Phase 3

Glucocorticoid Receptor

GPCR/G protein

FDA-approved_Drug_Library; GPCR/G protein Compound Library; MCE online Bioactive Compound Library

[1] Young PG, Skinner SJ, Black PN. Effects of glucocorticoids and beta-adrenoceptor agonists on the proliferation of airway smooth muscle. Eur J Pharmacol. 1995 Jan 24;273(1-2):137-43. [2] Nicolini G, Cremonesi G, Melani AS. Inhaled corticosteroid therapy with nebulized beclometasone dipropionate. Pulm Pharmacol Ther. 2010 Jun;23(3):145-55. [3] Delacourt C, Dutau G, Lefran?ois G, Comparison of the efficacy and safety of nebulized beclometasone dipropionate and budesonide in severe persistent childhood asthma. Respir Med. 2003 Feb;97 Suppl B:S27-33.

[1] http://www.ncbi.nlm.nih.gov/pubmed/7737307 [2] http://www.ncbi.nlm.nih.gov/pubmed/19961948 [3] http://www.ncbi.nlm.nih.gov/pubmed/12593525

EOS XFZ-00047

Methoxyphenamine (Hydrochloride)

5588/10/3

NSC-65644

C11H18ClNO

215.7197

COC1=CC=CC=C1CC(C)NC.[H]Cl

DMSO: ≥ 34 mg/mL

Launched

Inflammation/Immunology

Methoxyphenamine Hydrochloride is a β-adrenergic receptor agonist of the amphetamine class used as a bronchodilator. Target: β-adrenergic receptor

Adrenergic Receptor

GPCR/G protein

FDA-approved_Drug_Library; GPCR/G protein Compound Library; MCE online Bioactive Compound Library

EOS XFZ-00048

Proparacaine (Hydrochloride)

5875/6/9

Proxymetacaine Hydrochloride

C16H27ClN2O3

330.8502

O=C(OCCN(CC)CC)C1=CC=C(OCCC)C(N)=C1.[H]Cl

10 mM in DMSO

No Development Reported

Neurological Disease

Proparacaine Hydrochloride is a voltage-gated sodium channels antagonist with ED50 of 3.4 mM. IC50 Value: 3.4 mM(ED50) [1] Target: Sodium Channel in vitro: Proparacaine is more potent and less toxic than cocaine [1]. Proparacaine significantly increases in FHV-1 (P < 0.01), C. felis, and 28S rDNA Ct values when fusidic acid is used [2]. in vivo: Proparacaine inhibits corneal epithelial migration and adhesion through alteration of the actin cytoskeleton [3]. Proparacaine acts like bupivacaine or lidocaine and produces dose-related spinal blockades of motor function, proprioception and nociception. Intrathecal proxymetacaine also produces longer sensory blockade than motor blockade [4].

Sodium Channel

Membrane Transporter/Ion Channel

Clinical Compound Library; MCE online Bioactive Compound Library; Membrane Tranporter/Ion Channel Compound Library

[1] Grant, R.L. and D. Acosta, Comparative toxicity of tetracaine, proparacaine and cocaine evaluated with primary cultures of rabbit corneal epithelial cells. Exp Eye Res, 1994. 58(4): p. 469-78. [2] Segarra, S., K. Papasouliotis, and C. Helps, The in vitro effects of proxymetacaine, fluorescein, and fusidic acid on real-time PCR assays used for the diagnosis of Feline herpesvirus 1 and Chlamydophila felis infections. Vet Ophthalmol, 2011. 14 Suppl 1: p. 5-8. [3] Dass, B.A., H.K. Soong, and B. Lee, Effects of proparacaine on actin cytoskeleton of corneal epithelium. J Ocul Pharmacol, 1988. 4(3): p. 187-94. [4] Hung, C.H., et al., Intrathecal oxybuprocaine and proxymetacaine produced potent and long-lasting spinal anesthesia in rats. Neurosci Lett, 2009. 454(3): p. 249-53.

[1] http://www.ncbi.nlm.nih.gov/pubmed/7925683 [2] http://www.ncbi.nlm.nih.gov/pubmed/21923818 [3] http://www.ncbi.nlm.nih.gov/pubmed/3198982 [4] http://www.ncbi.nlm.nih.gov/pubmed/19429093

EOS Med Chem, Medicinal Chemical is Big

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2016 China CPHI meet