Biggest Manufacturer Acalabrutinib (ACP-196) CAS#: 1420477-60-6 and Intermediates.

Name: Acalabrutinib (ACP-196)

CAS#: 1420477-60-6

Chemical Formula: C26H23N7O2

Exact Mass: 465.19132

Molecular Weight: 465.52

Elemental Analysis: C, 67.08; H, 4.98; N, 21.06; O, 6.87

EOS Med Chem produce Acalabrutinib (ACP-196) in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

First supplier who could produce EE, Optical purity 99.5 more, stock more than 20KG.

Acalabrutinib (ACP-196) Intermediates, EOS Med Chem have 8; Acalabrutinib (ACP-196) Impurity we have 10, all from GMP, FDA plant.

Now Acalabrutinib (ACP-196) DMF document is preparing.

Until 2016, Aug, Acalabrutinib (ACP-196) more than produced 25kg API, 120kg Intermediates, world biggest supplier.

Acalabrutinib (ACP-196) Intermediate 1420478-90-5,(S)-4-(8-amino-3-(pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 1420478-89-2,(S)-benzyl 2-(8-amino-1-(4-(pyridin-2-ylcarbamoyl)phenyl)imidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 1420478-88-1, (S)-benzyl 2-(8-amino-1-bromoimidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 1420478-87-0,(S)-benzyl 2-(1-bromo-8-chloroimidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 1418307-18-2, (S)-benzyl 2-(8-chloroimidazo[1,5-a]pyrazin-3-yl)pyrrolidine-1-carboxylate, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 1418307-17-1, (S)-benzyl 2-((3-chloropyrazin-2-yl)methylcarbamoyl)pyrrolidine-1-carboxylate, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 771581-15-8,  2-Aminomethyl-3-chloropyrazine, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 55557-52-3, 3-Chloropyrazine-2-carbonitrile, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 1383385-64-5, No Name, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

Acalabrutinib (ACP-196) Intermediate 180516-87-4, 4-Carboxylphenylboronic acid pinacol ester, HPLC99%, NMR, LCMS is ok, more than 100g in stock.

2017 China CPHI: E1M35

EOS Med Chem, Medchem is Big

執大象，天下往，往而無害，安平泰

網址: www.eosmedchem.com 

労働時間: Beijing Time 4:00AM~11:00PM

郵箱: info@eosmedchem.com ; eosmedchem@gmail.com 

辦公室: 0086-531-69905422-806(直通)

攜帶番號 & WhatsApp & Wechat: +8618653174435

住所: Diaozhen Chemical Industrial Park, Jinan City, China

Skype: willgutian

QQ: 2393923585

Description: Acalabrutinib, also known as ACP-196, is an orally available inhibitor of Bruton’s tyrosine kinase (BTK) with potential antineoplastic activity. Upon administration, ACP-196 inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. BTK, a member of the src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.

Synonym: ACP-196; ACP196; ACP 196; Acalabrutinib

IUPAC/Chemical Name: (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide

Acalabrutinib is a potent and selective BTK (Bruton's tyrosine kinase) inhibitor. BTK is a cytoplasmic, non-receptor tyrosine kinase that transmits signals from a variety of cell-surface molecules, including the B-cell receptor (BCR) and tissue homing receptors. Genetic BTK deletion causes B-cell immunodeficiency in humans and mice, making this kinase an attractive therapeutic target for B-cell disorders. BTK inhibitors targeting B cell receptor signaling and other survival mechanism showed great promise for the treatment of chronic lymphocytic leukemia (CLL)s holds great promise.

As of 2015 it is in late stage clinical trials for relapsed chronic lymphocytic leukemia. Interim results are encouraging : 95% overall response rate. It is also in another 20 clinical trials (alone and in combination) for various cancers.

1: Maly J, Blachly JS. Chronic Lymphocytic Leukemia: Exploiting Vulnerabilities with Targeted Agents. Curr Hematol Malig Rep. 2016 Feb 11. [Epub ahead of print] PubMed PMID: 26893063.

2: Byrd JC, Harrington B, O'Brien S, Jones JA, Schuh A, Devereux S, Chaves J, Wierda WG, Awan FT, Brown JR, Hillmen P, Stephens DM, Ghia P, Barrientos JC, Pagel JM, Woyach J, Johnson D, Huang J, Wang X, Kaptein A, Lannutti BJ, Covey T, Fardis M, McGreivy J, Hamdy A, Rothbaum W, Izumi R, Diacovo TG, Johnson AJ, Furman RR. Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016 Jan 28;374(4):323-32. doi: 10.1056/NEJMoa1509981. Epub 2015 Dec 7. PubMed PMID: 26641137.

EOS Med Chem produce Venetoclax (ABT199) 1257044-40-8 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok

Name: Venetoclax (ABT199)
CAS#: 1257044-40-8
Chemical Formula: C45H50ClN7O7S
Exact Mass: 867.3181
Molecular Weight: 868.44
Elemental Analysis: C, 62.24; H, 5.80; Cl, 4.08; N, 11.29; O, 12.90; S, 3.69

EOS Med Chem produce Venetoclax (ABT199) 1257044-40-8 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.
Venetoclax (ABT199) 1257044-40-8 Intermediates, EOS Med Chem have 8; Venetoclax (ABT199) 1257044-40-8 Impurity we have 10, all from GMP, FDA plant.
Now Venetoclax (ABT199) 1257044-40-8 DMF document is preparing.
Until 2016, Aug, Venetoclax (ABT199) 1257044-40-8 more than produced 25kg API, 120kg Intermediates

ABT-199, Venetoclax;  CAS 1257044-40-8

Venetoclax (ABT199) Intermediate 4-fluoro-3-nitrobenzenesulfonamide  CAS  406233-31-6
Venetoclax (ABT199) Intermediate 3-Nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)benzenesulfonamide       CAS 1228779-96-1
Venetoclax (ABT199) Intermediate 1H-Pyrrolo[2,3-b]pyridin-5-ol      CAS 98549-88-3
Venetoclax (ABT199) Intermediate Ethyl2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-fluorobenzoate  CAS 1630101-74-4
Venetoclax (ABT199) Intermediate Methyl 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-fluorobenzoate     CAS 1235865-75-4
Venetoclax (ABT199) Intermediate 3,3-Dimethylcyclohexanone  CAS 2979-19-3
Venetoclax (ABT199) Intermediate (4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methanol CAS 1228837-05-5
Venetoclax (ABT199) Intermediate 1-[[2-(4-Chlorophenyl)-4,4-dimethylcyclohex-1-enyl]methyl]piperazine   CAS 1228780-72-0
Venetoclax (ABT199) Intermediate Tert-butyl4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine-1-carboxylate     CAS 1228780-71-9
Venetoclax (ABT199) Intermediate 2-((1H-Pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)benzoic acid CAS 1235865-77-6

Description: Venetoclax, also known as ABT-199 or GDC0199, is an orally bioavailable, selective small molecule inhibitor of the anti-apoptotic protein Bcl-2, with potential antineoplastic activity. Venetoclax mimics BH3-only proteins, the native ligands of Bcl-2 and apoptosis activators, by binding to the hydrophobic groove of Bcl-2 proteins thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells.
Synonym: ABT199; ABT-199; ABT 199; GDC0199; GDC0199; GDC 0199; RG7601; RG7601; RG 7601. Venetoclax.
IUPAC/Chemical Name: 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide
SMILES Code: O=C(NS(=O)(C1=CC=C(NCC2CCOCC2)C([N+]([O-])=O)=C1)=O)C3=CC=C(N4CCN(CC5=C(C6=CC=C(Cl)C=C6)CC(C)(C)CC5)CC4)C=C3OC7=CN=C(NC=C8)C8=C7

GDC-0199 (RG7601) is a novel small molecule Bcl-2 selective inhibitor designed to restore apoptosis, also known as programmed cell death, by blocking the function of a pro-survival Bcl-2 family protein. The Bcl-2 family proteins, which are expressed at high levels in many tumors, play a central role in regulating apoptosis and, consequently, are thought to impact tumor formation, tumor growth and resistance.

1: Seymour J. ABT-199 for Chronic Lymphocytic Leukemia. Clin Adv Hematol Oncol. 2014 Oct;12(10):698-700. PubMed PMID: 25658896.
2: Choudhary GS, Al-Harbi S, Mazumder S, Hill BT, Smith MR, Bodo J, Hsi ED, Almasan A. MCL-1 and BCL-xL-dependent resistance to the BCL-2 inhibitor ABT-199 can be overcome by preventing PI3K/AKT/mTOR activation in lymphoid malignancies. Cell Death Dis. 2015 Jan 15;6:e1593. doi: 10.1038/cddis.2014.525. PubMed PMID: 25590803.
3: Cao Y, Yang G, Hunter ZR, Liu X, Xu L, Chen J, Tsakmaklis N, Hatjiharissi E, Kanan S, Davids MS, Castillo JJ, Treon SP. The BCL2 antagonist ABT-199 triggers apoptosis, and augments ibrutinib and idelalisib mediated cytotoxicity in CXCR4(Wild-type) and CXCR4(WHIM) mutated Waldenstrom macroglobulinaemia cells. Br J Haematol. 2015 Jan 12. doi: 10.1111/bjh.13278. [Epub ahead of print] PubMed PMID: 25582069.
4: Johnson-Farley N, Veliz J, Bhagavathi S, Bertino JR. ABT-199, a BH3 mimetic that specifically targets Bcl-2, enhances the antitumor activity of chemotherapy, bortezomib and JQ1 in "double hit" lymphoma cells. Leuk Lymphoma. 2015 Jan 28:1-7. [Epub ahead of print] PubMed PMID: 25373508.
5: Ko TK, Chuah CT, Huang JW, Ng KP, Ong ST. The BCL2 inhibitor ABT-199 significantly enhances imatinib-induced cell death in chronic myeloid leukemia progenitors. Oncotarget. 2014 Oct 15;5(19):9033-8. PubMed PMID: 25333252; PubMed Central PMCID: PMC4253416.
6: Peirs S, Matthijssens F, Goossens S, Van de Walle I, Ruggero K, de Bock CE, Degryse S, Canté-Barrett K, Briot D, Clappier E, Lammens T, De Moerloose B, Benoit Y, Poppe B, Meijerink JP, Cools J, Soulier J, Rabbitts TH, Taghon T, Speleman F, Van Vlierberghe P. ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia. Blood. 2014 Dec 11;124(25):3738-47. doi: 10.1182/blood-2014-05-574566. Epub 2014 Oct 9. PubMed PMID: 25301704.
7: Zhao X, Bodo J, Sun D, Durkin L, Lin J, Smith MR, Hsi ED. Combination of ibrutinib with ABT-199: synergistic effects on proliferation inhibition and apoptosis in mantle cell lymphoma cells through perturbation of BTK, AKT and BCL2 pathways. Br J Haematol. 2015 Mar;168(5):765-8. doi: 10.1111/bjh.13149. Epub 2014 Oct 4. PubMed PMID: 25284608.
8: ABT-199 shows effectiveness in CLL. Cancer Discov. 2014 Sep;4(9):OF7. doi: 10.1158/2159-8290.CD-NB2014-102. Epub 2014 Jul 3. PubMed PMID: 25185206.
9: Chonghaile TN, Roderick JE, Glenfield C, Ryan J, Sallan SE, Silverman LB, Loh ML, Hunger SP, Wood B, DeAngelo DJ, Stone R, Harris M, Gutierrez A, Kelliher MA, Letai A. Maturation stage of T-cell acute lymphoblastic leukemia determines BCL-2 versus BCL-XL dependence and sensitivity to ABT-199. Cancer Discov. 2014 Sep;4(9):1074-87. doi: 10.1158/2159-8290.CD-14-0353. Epub 2014 Jul 3. PubMed PMID: 24994123; PubMed Central PMCID: PMC4154982.
10: Wei A. ABT-199 partners with azacitidine to contest myeloid malignancies. Leuk Lymphoma. 2015 Jan;56(1):8-9. doi: 10.3109/10428194.2014.919638. Epub 2014 Jul 15. PubMed PMID: 24794804.

EOS Med Chem produce Tirabrutinib HCl,ONO4059, 1439901-97-9 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Name: Tirabrutinib HCl

CAS#: 1439901-97-9 (HCl)

Chemical Formula: C25H23ClN6O3

Exact Mass:

Molecular Weight: 490.948

Elemental Analysis: C, 61.16; H, 4.72; Cl, 7.22; N, 17.12; O, 9.78

EOS Med Chem produce Tirabrutinib HCl,ONO4059, 1439901-97-9 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Tirabrutinib HCl,ONO4059, 1439901-97-9 Intermediates, EOS Med Chem have 8; Tirabrutinib HCl,ONO4059, 1439901-97-9 Impurity we have 10, all from GMP, FDA plant.

Now Tirabrutinib HCl,ONO4059, 1439901-97-9 DMF document is preparing.

Until 2016, Aug, Tirabrutinib HCl,ONO4059, 1439901-97-9 more than produced 25kg API, 120kg Intermediates

Description: Tirabrutinib HCl, also known as ONO-4059 HCl, is a potent and orally active Bruton agammaglobulinemia tyrosine kinase (BTK) in hibitor. Upon administration, ONO-4059 covalently binds to BTK within B cells, thereby preventing B-cell receptor signaling and impeding B-cell development. As a result, this agent may inhibit the proliferation of B-cell malignancies. BTK, a cytoplasmic tyrosine kinase and member of the Tec family of kinases, plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.

Synonym: ONO-4059 HCl; ONO4059; ONO 4059; ONO-4059; GS 4059; GS-4059; GS4059; ONO-WG-307; Tirabrutinib

IUPAC/Chemical Name: (R)-6-amino-9-(1-(but-2-ynoyl)pyrrolidin-3-yl)-7-(4-phenoxyphenyl)-7,9-dihydro-8H-purin-8-one hydrochloride

SMILES Code: O=C(N1C[C@@H](CC1)N(C2=O)C3=NC=NC(N)=C3N2C4=CC=C(C=C4)OC5=CC=CC=C5)C#CC.[H]Cl

Related CAS#

1439901-97-9 (ONO-4059 HCl);

1351636-18-4 (ONO-4059 free base).

1351635-67-0 (ONO-4059 analog).

CID: PMC4876096.

2: Wu J, Zhang M, Liu D. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol. 2016 Mar 9;9:21. doi: 10.1186/s13045-016-0250-9. PubMed PMID: 26957112; PubMed Central PMCID: PMC4784459.

3: Walter HS, Rule SA, Dyer MJ, Karlin L, Jones C, Cazin B, Quittet P, Shah N, Hutchinson CV, Honda H, Duffy K, Birkett J, Jamieson V, Courtenay-Luck N, Yoshizawa T, Sharpe J, Ohno T, Abe S, Nishimura A, Cartron G, Morschhauser F, Fegan C, Salles G. A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies. Blood. 2016 Jan 28;127(4):411-9. doi: 10.1182/blood-2015-08-664086. Epub 2015 Nov 5. PubMed PMID: 26542378; PubMed Central PMCID: PMC4731845.

4: Robak P, Smolewski P, Robak T. Emerging immunological drugs for chronic lymphocytic leukemia. Expert Opin Emerg Drugs. 2015 Sep;20(3):423-47. doi: 10.1517/14728214.2015.1046432. Epub 2015 Jul 11. Review. PubMed PMID: 26153226.

5: Burger JA. Bruton's tyrosine kinase (BTK) inhibitors in clinical trials. Curr Hematol Malig Rep. 2014 Mar;9(1):44-9. doi: 10.1007/s11899-013-0188-8. Review. PubMed PMID: 24357428.

6: Akinleye A, Chen Y, Mukhi N, Song Y, Liu D. Ibrutinib and novel BTK inhibitors in clinical development. J Hematol Oncol. 2013 Aug 19;6:59. doi: 10.1186/1756-8722-6-59. Review. PubMed PMID: 23958373; PubMed Central PMCID: PMC3751776.

EOS Med Chem produce AT-7519,902135-91-5 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Name: AT-7519 HCl
CAS#: 902135-91-5 (HCl salt)
Chemical Formula: C16H17Cl2N5O2
Exact Mass:
Molecular Weight: 418.71
Elemental Analysis: C, 45.90; H, 4.33; Cl, 25.40; N, 16.73; O, 7.6


EOS Med Chem produce AT-7519,902135-91-5 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.
AT-7519,902135-91-5 Intermediates, EOS Med Chem have 8; AT-7519,902135-91-5 Impurity we have 10, all from GMP, FDA plant.
Now AT-7519,902135-91-5 DMF document is preparing.
Until 2016, Aug, AT-7519,902135-91-5 more than produced 25kg API, 120kg Intermediates

GMP PRODUCE:

Alectinib;Veliparib;Acalabrutinib;Venetoclax;Sotagliflozin;Ledipasvir;LX1606;Anacetrapib;Abemaciclib 

2016 Mumbai CPHI, Hope to meet!

2016 Barcelona CPHI, Hope to meet!

2016 Korea(한국) CPHI, C40, Welcome!

2016 Shanghai CPHI, W5C47, Welcome!

EOS Med Chem, Medchem is Big

執大象，天下往，往而無害，安平泰

網址: www.eosmedchem.com 

郵箱: gutian@eosmedchem.com; eosmedchem@gmail.com 

辦公室: 0086-531-69905422-806(直通)

攜帶番號 & WhatsApp: +8618653174435

Skype: willgutian

AT-7519 AT-7519 844442-38-2(free base)
AT-7519M AT-7519M 902135-91-5(HCl)
AT-7519 Intermediates 4-[(4-amino-1H-pyrazole-3-carbonyl)amino]piperidine-1-carboxylic acid tert-butyl ester 844443-81-8
AT-7519 Intermediates 4-(2,6-dichloro-benzoylamino)-1H-pyrazole-3-carboxylic acid 825619-04-3


Description: AT-7519 is an orally bioavailable small molecule CDK inhibitor with potential antineoplastic activity. AT7519M selectively binds to and inhibits cyclin dependent kinases (CDKs), which may result in cell cycle arrest, induction of apoptosis, and inhibition of tumor cell proliferation. CDKs are serine/theronine kinases involved in regulation of the cell cycle and may be overexpressed in some types of cancer cells.
Synonym: AT7519; AT-7519; AT 7519.
IUPAC/Chemical Name: N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide hydrochloride
SMILES Code: O=C(C1=NNC=C1NC(C2=C(Cl)C=CC=C2Cl)=O)NC3CCNCC3.[H]Cl


Related:
902135-91-5 (AT-7519 HCl salt)
844442-38-2 (AT-7519 free base)
1: Lucas CD, Dorward DA, Tait MA, Fox S, Marwick JA, Allen KC, Robb CT, Hirani N, Haslett C, Duffin R, Rossi AG. Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung. Mucosal Immunol. 2013 Nov 27. doi: 10.1038/mi.2013.102. [Epub ahead of print] PubMed PMID: 24280938.
2: Dolman ME, den Hartog IJ, Molenaar JJ, Schellens JH, Beijnen JH, Sparidans RW. Liquid chromatography-tandem mass spectrometric assay for the cyclin-dependent kinase inhibitor AT7519 in mouse plasma. J Pharm Biomed Anal. 2014 Jan 25;88:216-20. doi: 10.1016/j.jpba.2013.08.051. Epub 2013 Sep 12. PubMed PMID: 24080524.
3: Alessandri AL, Duffin R, Leitch AE, Lucas CD, Sheldrake TA, Dorward DA, Hirani N, Pinho V, de Sousa LP, Teixeira MM, Lyons JF, Haslett C, Rossi AG. Induction of eosinophil apoptosis by the cyclin-dependent kinase inhibitor AT7519 promotes the resolution of eosinophil-dominant allergic inflammation. PLoS One. 2011;6(9):e25683. doi: 10.1371/journal.pone.0025683. Epub 2011 Sep 30. PubMed PMID: 21984938; PubMed Central PMCID: PMC3184151.
4: Mahadevan D, Plummer R, Squires MS, Rensvold D, Kurtin S, Pretzinger C, Dragovich T, Adams J, Lock V, Smith DM, Von Hoff D, Calvert H. A phase I pharmacokinetic and pharmacodynamic study of AT7519, a cyclin-dependent kinase inhibitor in patients with refractory solid tumors. Ann Oncol. 2011 Sep;22(9):2137-43. doi: 10.1093/annonc/mdq734. Epub 2011 Feb 16. PubMed PMID: 21325451.
5: Squires MS, Cooke L, Lock V, Qi W, Lewis EJ, Thompson NT, Lyons JF, Mahadevan D. AT7519, a cyclin-dependent kinase inhibitor, exerts its effects by transcriptional inhibition in leukemia cell lines and patient samples. Mol Cancer Ther. 2010 Apr;9(4):920-8. doi: 10.1158/1535-7163.MCT-09-1071. Epub 2010 Mar 30. PubMed PMID: 20354122.
6: Santo L, Vallet S, Hideshima T, Cirstea D, Ikeda H, Pozzi S, Patel K, Okawa Y, Gorgun G, Perrone G, Calabrese E, Yule M, Squires M, Ladetto M, Boccadoro M, Richardson PG, Munshi NC, Anderson KC, Raje N. AT7519, A novel small molecule multi-cyclin-dependent kinase inhibitor, induces apoptosis in multiple myeloma via GSK-3beta activation and RNA polymerase II inhibition. Oncogene. 2010 Apr 22;29(16):2325-36. doi: 10.1038/onc.2009.510. Epub 2010 Jan 25. PubMed PMID: 20101221; PubMed Central PMCID: PMC3183744.
7: Squires MS, Feltell RE, Wallis NG, Lewis EJ, Smith DM, Cross DM, Lyons JF, Thompson NT. Biological characterization of AT7519, a small-molecule inhibitor of cyclin-dependent kinases, in human tumor cell lines. Mol Cancer Ther. 2009 Feb;8(2):324-32. doi: 10.1158/1535-7163.MCT-08-0890. Epub 2009 Jan 27. PubMed PMID: 19174555.
8: Wyatt PG, Woodhead AJ, Berdini V, Boulstridge JA, Carr MG, Cross DM, Davis DJ, Devine LA, Early TR, Feltell RE, Lewis EJ, McMenamin RL, Navarro EF, O'Brien MA, O'Reilly M, Reule M, Saxty G, Seavers LC, Smith DM, Squires MS, Trewartha G, Walker MT, Woolford AJ. Identification of N-(4-piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), a novel cyclin dependent kinase inhibitor using fragment-based X-ray crystallography and structure based drug design. J Med Chem. 2008 Aug 28;51(16):4986-99. doi: 10.1021/jm800382h. Epub 2008 Jul 26. PubMed PMID: 18656911.

EOS Med Chem produce Palbociclib,PD-0332991, 827022-32-2 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Name: Palbociclib HCl

CAS#: 827022-32-2 (HCl)

Chemical Formula: C24H29N7O2

Exact Mass:

Molecular Weight: 483.99

Elemental Analysis: C, 59.56; H, 6.25; Cl, 7.33; N, 20.26; O, 6.61

GMP PRODUCE:

Alectinib;Veliparib;Acalabrutinib;Venetoclax;Sotagliflozin;Ledipasvir;LX1606;Anacetrapib;Abemaciclib 

2016 Mumbai CPHI, Hope to meet!

2016 Barcelona CPHI, Hope to meet!

2016 Korea(한국) CPHI, C40, Welcome!

2016 Shanghai CPHI, W5C47, Welcome!

EOS Med Chem, Medchem is Big

執大象，天下往，往而無害，安平泰

網址: www.eosmedchem.com 

郵箱: gutian@eosmedchem.com; eosmedchem@gmail.com 

辦公室: 0086-531-69905422-806(直通)

攜帶番號 & WhatsApp: +8618653174435

Skype: willgutian

EOS Med Chem produce Palbociclib,PD-0332991, 827022-32-2 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Palbociclib,PD-0332991, 827022-32-2 Intermediates, EOS Med Chem have 8; Palbociclib,PD-0332991, 827022-32-2 Impurity we have 10, all from GMP, FDA plant.

Now Palbociclib,PD-0332991, 827022-32-2 DMF document is preparing.

Until 2016, Aug, Palbociclib,PD-0332991, 827022-32-2 more than produced 25kg API, 120kg Intermediates

Palbociclib Ibrance;PD-0332991;Palbociclib;; 571190-30-2(free base)

Palbociclib HCl Ibrance;PD-0332991;Palbociclib;PD-0332991 HCl; 827022-32-2(HCl)

Palbociclib Intermediates 1-(6-nitropyridin-3-yl)piperazine 775288-71-6

Palbociclib Intermediates tert-butyl 4-(6-nitropyridin-3-yl)piperazine-1-carboxylate 571189-16-7

Palbociclib Intermediates 6-bromo-2-chloro-8-cyclopentyl-5-methylpyrido[2,3-d]pyrimidin-7(8H)-one 1016636-76-2

Palbociclib Intermediates 5-bromo-2-chloro-N-cyclopentylpyrimidin-4-amine 733039-20-8

Palbociclib Intermediates 2-chloro-8-cyclopentyl-5-Methylpyrido[2,3-d]pyriMidin-7(8H)-one 1013916-37-4

Palbociclib Intermediates Tert-butyl 4-(6-aminopyridin-3-yl)piperazine-1-carboxylate 571188-59-5

Palbociclib Intermediates Tert-butyl 4-(6-((6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate 571188-82-4

Palbociclib Intermediates Tert-butyl 4-(6-((6-(1-butoxyvinyl)-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)pyridin-3-yl)piperazine-1-carboxylate

Palbociclib Intermediates 6-bromo-8-cyclopentyl-5-methyl-2-(methylsulfinyl)pyrido[2,3-d]pyrimidin-7(8H)-one 571188-81-3

Palbociclib Intermediates Ethyl 4-(cyclopentylamino)-2-(methylthio)pyrimidine-5-carboxylate 211245-62-4

Palbociclib Intermediates (4-(cyclopentylamino)-2-(methylthio)pyrimidin-5-yl)methanol 211245-63-5

Palbociclib Intermediates 4-(cyclopentylamino)-2-(methylthio)pyrimidine-5-carbaldehyde 211245-64-6

Palbociclib Intermediates 1-(4-(cyclopentylamino)-2-(methylthio)pyrimidin-5-yl)ethanol 362656-31-3

Palbociclib Intermediates 8-cyclopentyl-5-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one 362656-23-3

Description: Palbociclib, also known as PD0332991, is an orally available pyridopyrimidine-derived cyclin-dependent kinase (CDK) inhibitor with potential antineoplastic activity. PD-0332991 selectively inhibits cyclin-dependent kinases (particularly Cdk4/cyclin D1 kinase), which may inhibit retinoblastoma (Rb) protein phosphorylation; inhibition of Rb phosphorylation prevents Rb-positive tumor cells from entering the S phase of the cell cycle (arrest in the G1 phase), resulting in suppression of DNA replication and decreased tumor cell proliferation. PD 0332991 is a highly specific inhibitor of cyclin-dependent kinase 4 (Cdk4) (IC50 = 0.011 μmol/L) and Cdk6 (IC50 = 0.016 μmol/L), having no activity against a panel of 36 additional protein kinases. Palbociclib was approved on 2/3/2015 for treatment of advanced (metastatic) breast cancer.

Synonym: PD 0332991; PD-0332991; PD0332991; PD0332991; PD332991; PD-332991; PD 332991; Palbociclib, brand name: Ibrance

IUPAC/Chemical Name: 6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one hydrochloride

SMILES Code: O=C1C(C(C)=O)=C(C)C2=CN=C(NC3=NC=C(N4CCNCC4)C=C3)N=C2N1C5CCCC5.[H]Cl

CAS# related to Palbociclib

CAS#571190-30-2 (Palbociclib free base);

CAS# 827022-32-2 ( PalbociclibHCl salt);

CAS#827022-33-3 (Palbociclib Isethionate)

1: L'Allemain G. [Doubling time of progression-free survival by palbociclib in metastatic breast cancer]. Bull Cancer. 2015 Apr;102(4):300. doi: 10.1016/j.bulcan.2015.02.011. French. PubMed PMID: 26042255.

2: Palbociclib Extends Survival in Advanced Breast Cancer. Cancer Discov. 2015 Jun 2. [Epub ahead of print] PubMed PMID: 26036642.

3: Turner NC, Ro J, André F, Loi S, Verma S, Iwata H, Harbeck N, Loibl S, Huang Bartlett C, Zhang K, Giorgetti C, Randolph S, Koehler M, Cristofanilli M. Palbociclib in Hormone-Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2015 Jun 1. [Epub ahead of print] PubMed PMID: 26030518.

4: Niesvizky R, Badros AZ, Costa LJ, Ely SA, Singhal SB, Stadtmauer EA, Haideri NA, Yacoub A, Hess G, Lentzsch S, Spicka I, Chanan-Khan AA, Raab MS, Tarantolo S, Vij R, Zonder JA, Huang X, Jayabalan D, Di Liberto M, Huang X, Jiang Y, Kim ST, Randolph S, Chen-Kiang S. Phase 1/2 study of cyclin-dependent kinase (CDK)4/6 inhibitor palbociclib (PD-0332991) with bortezomib and dexamethasone in relapsed/refractory multiple myeloma. Leuk Lymphoma. 2015 May 15:1-9. [Epub ahead of print] PubMed PMID: 25813205.

5: Dhillon S. Palbociclib: first global approval. Drugs. 2015 Apr;75(5):543-51. doi: 10.1007/s40265-015-0379-9. PubMed PMID: 25792301.

6: Finn RS, Crown JP, Lang I, Boer K, Bondarenko IM, Kulyk SO, Ettl J, Patel R, Pinter T, Schmidt M, Shparyk Y, Thummala AR, Voytko NL, Fowst C, Huang X, Kim ST, Randolph S, Slamon DJ. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. doi: 10.1016/S1470-2045(14)71159-3. Epub 2014 Dec 16. PubMed PMID: 25524798.

7: Vaughn DJ, Hwang WT, Lal P, Rosen MA, Gallagher M, O'Dwyer PJ. Phase 2 trial of the cyclin-dependent kinase 4/6 inhibitor palbociclib in patients with retinoblastoma protein-expressing germ cell tumors. Cancer. 2015 May 1;121(9):1463-8. doi: 10.1002/cncr.29213. Epub 2014 Dec 18. PubMed PMID: 25522918.

8: DeMichele A, Clark AS, Tan KS, Heitjan DF, Gramlich K, Gallagher M, Lal P, Feldman M, Zhang P, Colameco C, Lewis D, Langer M, Goodman N, Domchek S, Gogineni K, Rosen M, Fox K, O'Dwyer P. CDK 4/6 inhibitor palbociclib (PD0332991) in Rb+ advanced breast cancer: phase II activity, safety, and predictive biomarker assessment. Clin Cancer Res. 2015 Mar 1;21(5):995-1001. doi: 10.1158/1078-0432.CCR-14-2258. Epub 2014 Dec 11. PubMed PMID: 25501126.

9: Altenburg JD, Farag SS. The potential role of PD0332991 (Palbociclib) in the treatment of multiple myeloma. Expert Opin Investig Drugs. 2015 Feb;24(2):261-71. doi: 10.1517/13543784.2015.993753. Epub 2014 Dec 13. PubMed PMID: 25494820.

10: Schultz KA, Petronio J, Bendel A, Patterson R, Vaughn DJ. PD0332991 (Palbociclib) for treatment of pediatric intracranial growing teratoma syndrome. Pediatr Blood Cancer. 2015 Jun;62(6):1072-4. doi: 10.1002/pbc.25338. Epub 2014 Nov 21. PubMed PMID: 25417786.

11: de Melo-Diogo D, Gaspar VM, Costa EC, Moreira AF, Oppolzer D, Gallardo E, Correia IJ. Combinatorial delivery of Crizotinib-Palbociclib-Sildenafil using TPGS-PLA micelles for improved cancer treatment. Eur J Pharm Biopharm. 2014 Nov;88(3):718-29. doi: 10.1016/j.ejpb.2014.09.013. Epub 2014 Oct 13. PubMed PMID: 25308930.

12: Cadoo KA, Gucalp A, Traina TA. Palbociclib: an evidence-based review of its potential in the treatment of breast cancer. Breast Cancer (Dove Med Press). 2014 Aug 4;6:123-33. doi: 10.2147/BCTT.S46725. eCollection 2014. Review. PubMed PMID: 25177151; PubMed Central PMCID: PMC4128689.

13: Pauls E, Badia R, Torres-Torronteras J, Ruiz A, Permanyer M, Riveira-Muñoz E, Clotet B, Marti R, Ballana E, Esté JA. Palbociclib, a selective inhibitor of cyclin-dependent kinase4/6, blocks HIV-1 reverse transcription through the control of sterile α motif and HD domain-containing protein-1 (SAMHD1) activity. AIDS. 2014 Sep 24;28(15):2213-22. doi: 10.1097/QAD.0000000000000399. PubMed PMID: 25036183.

14: Palbociclib ups PFS in HER2-/ER+ breast cancer. Cancer Discov. 2014 Jun;4(6):624-5. doi: 10.1158/2159-8290.CD-NB2014-053. Epub 2014 Apr 6. PubMed PMID: 24891344.

15: Rocca A, Farolfi A, Bravaccini S, Schirone A, Amadori D. Palbociclib (PD 0332991) : targeting the cell cycle machinery in breast cancer. Expert Opin Pharmacother. 2014 Feb;15(3):407-20. doi: 10.1517/14656566.2014.870555. Epub 2013 Dec 26. Review. PubMed PMID: 24369047.

EOS Med Chem produce EW-7197 1352608-82-2 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Name: EW-7197
CAS#: 1352608-82-2
Chemical Formula: C22H18FN7
Exact Mass: 399.1608
Molecular Weight: 399.4334
Elemental Analysis: C, 66.15; H, 4.54; F, 4.76; N, 24.55


EOS Med Chem produce EW-7197 1352608-82-2 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

EW-7197 1352608-82-2 Intermediates, EOS Med Chem have 8; EW-7197 1352608-82-2 Impurity we have 10, all from GMP, FDA plant.
Now EW-7197 1352608-82-2 DMF document is preparing.
Until 2016, Aug, EW-7197 1352608-82-2 more than produced 25kg API, 120kg Intermediates

GMP PRODUCE:

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TEW-7197 Intermediates N-(5-iodopyridin-2-yl)-N,N-dimethylmethanediamine
TEW-7197 Intermediates 6-iodo-[1,2,4]triazolo[1,5-a]pyridine 614750-84-4
TEW-7197 Intermediates [1,2,4]triazolo[1,5-a]pyridine-6-carbaldehyde 614750-81-1
TEW-7197 Intermediates diphenyl ((6-methylpyridin-2-yl)(phenylamino)methyl)phosphonate 614750-85-5
TEW-7197 Intermediates 2-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(6-methylpyridin-2-yl)ethanone 614750-82-2
TEW-7197 Intermediates 1-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-(6-methylpyridin-2-yl)ethane-1,2-dione 356560-84-4
TEW-7197 Intermediates 6-(2-(dimethoxymethyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)-[1,2,4]triazolo[1,5-a]pyridine 1352609-89-2
TEW-7197 Intermediates 4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazole-2-carbaldehyde 1352609-91-6


Description: TEW-7197, also known as EW-7197, is and orally bioavailable inhibitor of the serine/threonine kinase, transforming growth factor (TGF)-beta receptor type 1 (TGFBR1), also known as activin receptor-like kinase 5 (ALK5), with potential antineoplastic activity. Upon oral administration, TEW-7197 inhibits the activity of TGFBR1 and prevents TGF-beta/TGFBR1-mediated signaling. This suppresses tumor growth in TGFBR1-overexpressing tumor cells. TGFBR1, which is overexpressed in a variety of tumor cell types, plays a key role in tumor cell proliferation.
Synonym: TEW-7197; TEW 7197; TEW7197; EW-7197; EW 7197; EW7197.
IUPAC/Chemical Name: N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-fluoroaniline
SMILES Code: FC1=CC=CC=C1NCC2=NC(C3=CN4C(C=C3)=NC=N4)=C(C5=NC(C)=CC=C5)N2

1: Kim MJ, Park SA, Kim CH, Park SY, Kim JS, Kim DK, Nam JS, Sheen YY. TGF-β Type I Receptor Kinase Inhibitor EW-7197 Suppresses Cholestatic Liver Fibrosis by Inhibiting HIF1α-Induced Epithelial Mesenchymal Transition. Cell Physiol Biochem. 2016;38(2):571-88. doi: 10.1159/000438651. PubMed PMID: 26845171.
2: Naka K, Ishihara K, Jomen Y, Jin CH, Kim DH, Gu YK, Jeong ES, Li S, Krause DS, Kim DW, Bae E, Takihara Y, Hirao A, Oshima H, Oshima M, Ooshima A, Sheen YY, Kim SJ, Kim DK. Novel oral transforming growth factor-β signaling inhibitor EW-7197 eradicates CML-initiating cells. Cancer Sci. 2016 Feb;107(2):140-8. doi: 10.1111/cas.12849. PubMed PMID: 26583567; PubMed Central PMCID: PMC4768399.
3: Park SA, Kim MJ, Park SY, Kim JS, Lim W, Nam JS, Yhong Sheen Y. TIMP-1 mediates TGF-β-dependent crosstalk between hepatic stellate and cancer cells via FAK signaling. Sci Rep. 2015 Nov 9;5:16492. doi: 10.1038/srep16492. PubMed PMID: 26549110; PubMed Central PMCID: PMC4637930.
4: Krishnaiah M, Jin CH, Sheen YY, Kim DK. Synthesis and biological evaluation of 5-(fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl )imidazoles as inhibitors of transforming growth factor-β type I receptor kinase. Bioorg Med Chem Lett. 2015 Nov 15;25(22):5228-31. doi: 10.1016/j.bmcl.2015.09.058. PubMed PMID: 26483198.
5: Park SY, Kim MJ, Park SA, Kim JS, Min KN, Kim DK, Lim W, Nam JS, Sheen YY. Combinatorial TGF-β attenuation with paclitaxel inhibits the epithelial-to-mesenchymal transition and breast cancer stem-like cells. Oncotarget. 2015 Nov 10;6(35):37526-43. doi: 10.18632/oncotarget.6063. PubMed PMID: 26462028; PubMed Central PMCID: PMC4741946.
6: Park SA, Kim MJ, Park SY, Kim JS, Lee SJ, Woo HA, Kim DK, Nam JS, Sheen YY. EW-7197 inhibits hepatic, renal, and pulmonary fibrosis by blocking TGF-β/Smad and ROS signaling. Cell Mol Life Sci. 2015 May;72(10):2023-39. doi: 10.1007/s00018-014-1798-6. PubMed PMID: 25487606.
7: Son JY, Park SY, Kim SJ, Lee SJ, Park SA, Kim MJ, Kim SW, Kim DK, Nam JS, Sheen YY. EW-7197, a novel ALK-5 kinase inhibitor, potently inhibits breast to lung metastasis. Mol Cancer Ther. 2014 Jul;13(7):1704-16. doi: 10.1158/1535-7163.MCT-13-0903. PubMed PMID: 24817629.
8: Jin CH, Krishnaiah M, Sreenu D, Subrahmanyam VB, Rao KS, Lee HJ, Park SJ, Park HJ, Lee K, Sheen YY, Kim DK. Discovery of N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2 -yl)methyl)-2-fluoroaniline (EW-7197): a highly potent, selective, and orally bioavailable inhibitor of TGF-β type I receptor kinase as cancer immunotherapeutic/antifibrotic agent. J Med Chem. 2014 May 22;57(10):4213-38. doi: 10.1021/jm500115w. PubMed PMID: 24786585.
9: Sheen YY, Kim MJ, Park SA, Park SY, Nam JS. Targeting the Transforming Growth Factor-β Signaling in Cancer Therapy. Biomol Ther (Seoul). 2013 Sep 30;21(5):323-31. doi: 10.4062/biomolther.2013.072. Review. PubMed PMID: 24244818; PubMed Central PMCID: PMC3825194.
10: Yoon JH, Jung SM, Park SH, Kato M, Yamashita T, Lee IK, Sudo K, Nakae S, Han JS, Kim OH, Oh BC, Sumida T, Kuroda M, Ju JH, Jung KC, Park SH, Kim DK, Mamura M. Activin receptor-like kinase5 inhibition suppresses mouse melanoma by ubiquitin degradation of Smad4, thereby derepressing eomesodermin in cytotoxic T lymphocytes. EMBO Mol Med. 2013 Nov;5(11):1720-39. doi: 10.1002/emmm.201302524. Erratum in: EMBO Mol Med. 2014 May;6(5):703. PubMed PMID: 24127404; PubMed Central PMCID: PMC3840488.

EOS Med Chem produce Brigatinib (AP-26113) 1197953-54-0 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.

Name: Brigatinib (AP-26113)
CAS#: 1197953-54-0
Chemical Formula: C29H39ClN7O2P
Exact Mass: 583.25914
Molecular Weight: 584.10176
Elemental Analysis: C, 59.63; H, 6.73; Cl, 6.07; N, 16.79; O, 5.48; P, 5.30

EOS Med Chem produce Brigatinib (AP-26113) 1197953-54-0 in GMP plant, C-GMP standard, now COA, NMR, HPLC, MS is ok.


Brigatinib (AP-26113) 1197953-54-0 Intermediates, EOS Med Chem have 8; Brigatinib (AP-26113) 1197953-54-0 Impurity we have 10, all from GMP, FDA plant.
Now Brigatinib (AP-26113) 1197953-54-0 DMF document is preparing.
Until 2016, Aug, Brigatinib (AP-26113) 1197953-54-0 more than produced 25kg API, 120kg Intermediates

Brigatinib AP-26113 ； 1197953-54-0
Brigatinib Intermediates (2-((2,5-dichloropyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide 1197953-49-3


Description: Brigatinib, also known as AP-26113, is an orally active, potent and selective Dual ALK/EGFR inhibitor. AP26113 binds to and inhibits ALK kinase and ALK fusion proteins as well as EGFR and mutant forms. This leads to the inhibition of ALK kinase and EGFR kinase, disrupts their signaling pathways and eventually inhibits tumor cell growth in susceptible tumor cells. In addition, AP26113 appears to overcome mutation-based resistance. ALK belongs to the insulin receptor superfamily and plays an important role in nervous system development; ALK dysregulation and gene rearrangements are associated with a series of tumors. EGFR is overexpressed in a variety of cancer cell types.
Synonym: AP26113; AP-26113; AP 26113, Brigatinib
IUPAC/Chemical Name: (2-((5-chloro-2-((2-methoxy-4-(4-(4-methylpiperazin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)amino)phenyl)dimethylphosphine oxide
SMILES Code: CN1CCN(C2CCN(C3=CC=C(NC4=NC=C(Cl)C(NC5=CC=CC=C5P(C)(C)=O)=N4)C(OC)=C3)CC2)CC1


The following public resources have listed a wrong structure for Brigatinib (AP-26113)
1. Some papers:
Such as Onco Targets Ther. 2014 Mar 5;7:375-85., http://www.ncbi.nlm.nih.gov/pubmed/24623980.
2. Wikipedia (https://en.wikipedia.org/wiki/Brigatinib, last visited on 12/9/2015).
3. Sci-Finder Scholar Database: Before December 2015, Sci-Finder Scholar Database also wrongly listed CAS#1197958-12-5 as Brigatinib (AP26113). Now Sci-Finder Scholar Database has corrected.
4. Pubchem: https://pubchem.ncbi.nlm.nih.gov/compound/ap26113, last visited: 12/9/2015.
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--------------------------------------------------- More information related to AP26113 bioactivities---------------------------------------------
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AP26113 is a potent and selective ALK inhibitor. AP26113 induced tumor regression in BaF3 xenograft model expressing EML4-ALK, and EML4-ALK harboring G1269S and L1196M (gatekeeper) mutations. In preclinical studies, AP26113 was shown to be active against all 9 clinically-identified crizotinib-resistant mutants tested. AP26113 is also a potent, reversible inhibitor of activated and T790M-mutant EGFR, yet it does not inhibit the native enzyme [94]. A phase I/II study was initiated (NCT01449461) to evaluate AP26113 as a dual ALK/mutant EGFR inhibitor. As of 14 Jan 2013, 44 patients were enrolled including 37 with NSCLC. In the dose escalation phase (30-300 mg), two dose limiting toxicities were observed, grade 3 ALT elevations at 240 mg and grade 4 dyspnea at 300 mg. The recommended phase II dose was identified as 180 mg. The most common adverse effects were nausea (45%), fatigue (39%), diarrhea (27%). Among 18 evaluable ALK+ patients, four out of 5 patients with CNS lesions showed improvement on follow up imaging, including one patient resistant to crizotinib and ceritinib. Sixteen patients had EGFR mutation (EGFRm). Of 12 patients with EGFRm, one patient responded at 120 mg (duration 21 weeks, ongoing) and 6 patients had stable disease (2 ongoing, duration 7 and 31 weeks, respectively). In a later update, 114 pts were enrolled: 65 in phase 1 (30–300 mg) and 49 in phase 2 (180 mg) [93]. There were 106 pts with NSCLC. The most common treatment-emergent AEs (20%) were similar to the previous report. Early onset of pulmonary symptoms (dyspnea with hypoxia and/or findings on imaging) were observed in 6/45 (13%) pts at 180 mg QD. These symptoms needed urgent intervention. The respiratory symptoms were not observed at 90 mg QD (n = 8) or in the lead-in dose cohort (n = 19; initiated at 90 mg QD, escalated to 180 mg QD after 1 wk). Therefore, further enrollment with this dose escalation scheme, and an additional cohort of 90 mg QD without escalation were being added. Among 38 evaluable ALK+ NSCLC pts who had prior crizotinib, 24 (63%) reported response, including one CR. Six of 10 pts enrolled with untreated or progressing brain metastases showed response in brain, including 4 with complete resolution; 2 stable disease, 2 progressed; AP26113 has promising anti-tumor activity in pts with crizotinib-resistant ALK+ NSCLC, including pts with brain metastases. A randomized phase 2 trial of AP26113 comparing 90 mg QD vs. 90 mg QD escalating to 180 mg QD in crizotinib-resistant ALK+ NSCLC was planned. (copied from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349797/)


1: Noonan SA, Camidge DR. PROFILE 1014: lessons for the new era of lung cancer clinical research. Transl Lung Cancer Res. 2015 Oct;4(5):642-648. PubMed PMID: 26629438; PubMed Central PMCID: PMC4630507.
2: Correction: Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK-Positive Anaplastic Large Cell Lymphoma. Mol Cancer Res. 2015 Oct;13(10):1441. doi: 10.1158/1541-7786.MCR-15-0277. Epub 2015 Sep 29. PubMed PMID: 26420623.
3: Iams WT, Lovly CM. Anaplastic Lymphoma Kinase as a Therapeutic Target in Non-Small Cell Lung Cancer. Cancer J. 2015 Sep-Oct;21(5):378-82. doi: 10.1097/PPO.0000000000000142. PubMed PMID: 26389762.
4: Toyokawa G, Seto T, Takenoyama M, Ichinose Y. Insights into brain metastasis in patients with ALK+ lung cancer: is the brain truly a sanctuary? Cancer Metastasis Rev. 2015 Dec;34(4):797-805. doi: 10.1007/s10555-015-9592-y. PubMed PMID: 26342831; PubMed Central PMCID: PMC4661196.
5: Iragavarapu C, Mustafa M, Akinleye A, Furqan M, Mittal V, Cang S, Liu D. Novel ALK inhibitors in clinical use and development. J Hematol Oncol. 2015 Feb 27;8:17. doi: 10.1186/s13045-015-0122-8. PubMed PMID: 25888090; PubMed Central PMCID: PMC4349797.
6: Viala M, Brosseau S, Planchard D, Besse B, Soria JC. [Second generation ALK inhibitors in non-small cell lung cancer: systemic review]. Bull Cancer. 2015 Apr;102(4):381-9. doi: 10.1016/j.bulcan.2015.02.016. Epub 2015 Mar 25. Review. French. PubMed PMID: 25819217.
7: Mologni L, Ceccon M, Pirola A, Chiriano G, Piazza R, Scapozza L, Gambacorti-Passerini C. NPM/ALK mutants resistant to ASP3026 display variable sensitivity to alternative ALK inhibitors but succumb to the novel compound PF-06463922. Oncotarget. 2015 Mar 20;6(8):5720-34. PubMed PMID: 25749034; PubMed Central PMCID: PMC4467397.
8: Fontana D, Ceccon M, Gambacorti-Passerini C, Mologni L. Activity of second-generation ALK inhibitors against crizotinib-resistant mutants in an NPM-ALK model compared to EML4-ALK. Cancer Med. 2015 Jul;4(7):953-65. doi: 10.1002/cam4.413. Epub 2015 Feb 26. PubMed PMID: 25727400; PubMed Central PMCID: PMC4529334.
9: Pall G. The next-generation ALK inhibitors. Curr Opin Oncol. 2015 Mar;27(2):118-24. doi: 10.1097/CCO.0000000000000165. Review. PubMed PMID: 25588040.
10: Ma L, Zhang S. [Current status of targeted therapy for anaplastic lymphoma kinase in non-small cell lung cancer]. Zhongguo Fei Ai Za Zhi. 2014 Dec;17(12):850-4. doi: 10.3779/j.issn.1009-3419.2014.12.05. Review. Chinese. PubMed PMID: 25539610.
11: Stasi I, Cappuzzo F. Second generation tyrosine kinase inhibitors for the treatment of metastatic non-small-cell lung cancer. Transl Respir Med. 2014 Jan 6;2:2. doi: 10.1186/2213-0802-2-2. eCollection 2014. PubMed PMID: 25505694; PubMed Central PMCID: PMC4215821.
12: Ceccon M, Mologni L, Giudici G, Piazza R, Pirola A, Fontana D, Gambacorti-Passerini C. Treatment Efficacy and Resistance Mechanisms Using the Second-Generation ALK Inhibitor AP26113 in Human NPM-ALK-Positive Anaplastic Large Cell Lymphoma. Mol Cancer Res. 2015 Apr;13(4):775-83. doi: 10.1158/1541-7786.MCR-14-0157. Epub 2014 Nov 24. PubMed PMID: 25421750.
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