Original: Avadomide free base 1015474-32-4 , stock more than 100g

EOS med chem is the only manufacturer that provides excellent quality chemistry products and services at affordable rates. The experts working here are highly trained to handle these chemicals used in the creation of medicines used for treating various life-threatening diseases. We are into the manufacturing of chemical products after doing a deep research for the same.

EOS team of experts holds the work experience of more than ten years, and therefore we can assure you about the quality and superiority of the products and services we offer to all our valued clients around the globe. At present, this organization is listed among the most leading pharmaceutical suppliers around the world. We always supply products keeping the affordability in mind.

2018 CHINA CPHI, W4E82

EOS Med Chem, Medchem is Big
執大象，天下往，往而無害，安平泰
WEB: www.eosmedchem.com
EMAIL: info@eosmedchem.com; eosmedchem@gmail.com; eosmedchem@qq.com  
TEL: 0086-531-69905422
GMP PLANT: No. 37, Yulong Road, Qufu City, Shandong Province.

Description: Avadomide, also known as CC-122, is an orally available pleiotropic pathway modulator with potential antineoplastic activity. CC-122 mimics an interferon response and has antitumor activity in DLBCL CC-122 binds Cereblon (CRBN) and promotes degradation of Aiolos and Ikaros in diffuse large B-cell lymphoma (DLBCL) and T cells in vitro, in vivo, and in patients, resulting in both cell autonomous as well as immunostimulatory effects.

Name: Avadomide free base 

CAS#: 1015474-32-4 (free base) 

Chemical Formula: C14H14N4O3 

Exact Mass: 286.1066 

Molecular Weight: 286.291 

Elemental Analysis: C, 58.74; H, 4.93; N, 19.57; O, 16.77

Related CAS #: 1398053-45-6 (HCl)   1015474-32-4 (free base)    

Synonym: CC 122; CC-122; CC122, Avadomide

IUPAC/Chemical Name: 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione

InChi Key: RSNPAKAFCAAMBH-UHFFFAOYSA-N

InChi Code: InChI=1S/C14H14N4O3/c1-7-16-9-4-2-3-8(15)12(9)14(21)18(7)10-5-6-11(19)17-13(10)20/h2-4,10H,5-6,15H2,1H3,(H,17,19,20)

SMILES Code: O=C(C(N1C(C)=NC2=C(C(N)=CC=C2)C1=O)CC3)NC3=O

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code: 293490

ADDITIONAL INFORMATION

 In DLBCL cell lines, CC-122-induced degradation or short hairpin RNA-mediated knockdown of Aiolos and Ikaros correlates with increased transcription of interferon (IFN)-stimulated genes independent of IFN-α, -β, and -γ production and/or secretion and results in apoptosis in both activated B-cell (ABC) and germinal center B-cell DLBCL 

  

REFERENCES

1: Hagner PR, Man HW, Fontanillo C, Wang M, Couto S, Breider M, Bjorklund C, Havens CG, Lu G, Rychak E, Raymon H, Narla RK, Barnes L, Khambatta G, Chiu H, Kosek J, Kang J, Amantangelo MD, Waldman M, Lopez-Girona A, Cai T, Pourdehnad M, Trotter M, Daniel TO, Schafer PH, Klippel A, Thakurta A, Chopra R, Gandhi AK. CC-122, a pleiotropic pathway modifier, mimics an interferon response and has antitumor activity in DLBCL. Blood. 2015 Aug 6;126(6):779-89. doi: 10.1182/blood-2015-02-628669. Epub 2015 May 22. PubMed PMID: 26002965; PubMed Central PMCID: PMC4528065.

2: Li Y, Carayannopoulos LN, Thomas M, Palmisano M, Zhou S. Exposure-response analysis to assess the concentration-QTc relationship of CC-122. Clin Pharmacol. 2016 Sep 9;8:117-25. doi: 10.2147/CPAA.S111867. eCollection 2016. PubMed PMID: 27672344; PubMed Central PMCID: PMC5024774.

3: Krönke J, Fink EC, Hollenbach PW, MacBeth KJ, Hurst SN, Udeshi ND, Chamberlain PP, Mani DR, Man HW, Gandhi AK, Svinkina T, Schneider RK, McConkey M, Järås M, Griffiths E, Wetzler M, Bullinger L, Cathers BE, Carr SA, Chopra R, Ebert BL. Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS. Nature. 2015 Jul 9;523(7559):183-188. doi: 10.1038/nature14610. Epub 2015 Jul 1. PubMed PMID: 26131937; PubMed Central PMCID: PMC4853910.

4: Cubillos-Zapata C, Cordoba R, Avendaño-Ortiz J, Arribas-Jiménez C, Hernández-Jiménez E, Toledano V, Villaescusa T, Moreno V, López-Collazo E. CC-122 immunomodulatory effects in refractory patients with diffuse large B-cell lymphoma. Oncoimmunology. 2016 Sep 16;5(12):e1231290. doi: 10.1080/2162402X.2016.1231290. eCollection 2016. PubMed PMID: 28255524; PubMed Central PMCID: PMC5325046.

5: Jacques V, Czarnik AW, Judge TM, Van der Ploeg LH, DeWitt SH. Differentiation of antiinflammatory and antitumorigenic properties of stabilized enantiomers of thalidomide analogs. Proc Natl Acad Sci U S A. 2015 Mar 24;112(12):E1471-9. doi: 10.1073/pnas.1417832112. Epub 2015 Mar 9. Erratum in: Proc Natl Acad Sci U S A. 2015 May 12;112(19):E2553. PubMed PMID: 25775521; PubMed Central PMCID: PMC4378388.

6: Nowakowski GS. Evolution: IMiDs to PPMs, revolution in DLBCL? Blood. 2015 Aug 6;126(6):698-700. doi: 10.1182/blood-2015-06-649483. PubMed PMID: 26251224.

7: Ito T, Handa H. Recent topics in IMiDs and cereblon. Rinsho Ketsueki. 2017;58(10):2067-2073. doi: 10.11406/rinketsu.58.2067. PubMed PMID: 28978850.

8: Camicia R, Winkler HC, Hassa PO. Novel drug targets for personalized precision medicine in relapsed/refractory diffuse large B-cell lymphoma: a comprehensive review. Mol Cancer. 2015 Dec 11;14:207. doi: 10.1186/s12943-015-0474-2. Review. PubMed PMID: 26654227; PubMed Central PMCID: PMC4676894.

9: Cubillos-Zapata C, Córdoba R, Avendaño-Ortiz J, Lopez-Collazo E. Thalidomide analog CC-122 induces a refractory state in monocytes from patients with diffuse large B cell lymphoma. Leuk Lymphoma. 2017 Aug;58(8):1999-2001. doi: 10.1080/10428194.2016.1272686. Epub 2017 Jan 16. Retraction in: Leuk Lymphoma. 2017 Aug;58(8):I. PubMed PMID: 28093007.

Original: Emricasan 254750-02-2 , stock more than 100g

EOS med chem is the only manufacturer that provides excellent quality chemistry products and services at affordable rates. The experts working here are highly trained to handle these chemicals used in the creation of medicines used for treating various life-threatening diseases. We are into the manufacturing of chemical products after doing a deep research for the same.

EOS team of experts holds the work experience of more than ten years, and therefore we can assure you about the quality and superiority of the products and services we offer to all our valued clients around the globe. At present, this organization is listed among the most leading pharmaceutical suppliers around the world. We always supply products keeping the affordability in mind.

2018 CHINA CPHI, W4E82

EOS Med Chem, Medchem is Big
執大象，天下往，往而無害，安平泰
WEB: www.eosmedchem.com
EMAIL: info@eosmedchem.com; eosmedchem@gmail.com; eosmedchem@qq.com  
TEL: 0086-531-69905422
GMP PLANT: No. 37, Yulong Road, Qufu City, Shandong Province.

Description: Emricasan, also known as IDN 6556 and PF 03491390, is a first-in-class caspase inhibitor in clinical trials for the treatment of liver diseases. Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis. IDN6556 facilitates marginal mass islet engraftment in a porcine islet autotransplant model. Oral IDN-6556 may lower aminotransferase activity in patients with chronic hepatitis C. Orally-administered PF-03491390 is retained in the liver for prolonged periods with low systemic exposure, exerting a hepatoprotective effect against alpha-fas-induced liver injury in a mouse model.

Name: Emricasan 

CAS#: 254750-02-2 

Chemical Formula: C26H27F4N3O7 

Exact Mass: 569.17851 

Molecular Weight: 569.51 

Elemental Analysis: C, 54.83; H, 4.78; F, 13.34; N, 7.38; O, 19.66

Synonym: IDN-6556; IDN6556; IDN 6556; PF 03491390; PF-03491390; PF03491390; Emricasan.

IUPAC/Chemical Name: (S)-3-((S)-2-(2-((2-(tert-butyl)phenyl)amino)-2-oxoacetamido)propanamido)-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid

InChi Key: SCVHJVCATBPIHN-SJCJKPOMSA-N

InChi Code: InChI=1S/C26H27F4N3O7/c1-12(31-24(38)25(39)32-16-8-6-5-7-13(16)26(2,3)4)23(37)33-17(10-19(35)36)18(34)11-40-22-20(29)14(27)9-15(28)21(22)30/h5-9,12,17H,10-11H2,1-4H3,(H,31,38)(H,32,39)(H,33,37)(H,35,36)/t12-,17-/m0/s1

SMILES Code: O=C(O)C[C@H](NC([C@H](C)NC(C(NC1=CC=CC=C1C(C)(C)C)=O)=O)=O)C(COC2=C(F)C(F)=CC(F)=C2F)=O

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code: 293490

ADDITIONAL INFORMATION

   

   

  

REFERENCES

1: Rotman Y, Sanyal AJ. Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease. Gut. 2016 Sep 19. pii: gutjnl-2016-312431. doi: 10.1136/gutjnl-2016-312431. [Epub ahead of print] Review. PubMed PMID: 27646933.

2: Xu M, Lee EM, Wen Z, Cheng Y, Huang WK, Qian X, Tcw J, Kouznetsova J, Ogden SC, Hammack C, Jacob F, Nguyen HN, Itkin M, Hanna C, Shinn P, Allen C, Michael SG, Simeonov A, Huang W, Christian KM, Goate A, Brennand KJ, Huang R, Xia M, Ming GL, Zheng W, Song H, Tang H. Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nat Med. 2016 Oct;22(10):1101-1107. doi: 10.1038/nm.4184. PubMed PMID: 27571349.

3: Brumatti G, Ma C, Lalaoui N, Nguyen NY, Navarro M, Tanzer MC, Richmond J, Ghisi M, Salmon JM, Silke N, Pomilio G, Glaser SP, de Valle E, Gugasyan R, Gurthridge MA, Condon SM, Johnstone RW, Lock R, Salvesen G, Wei A, Vaux DL, Ekert PG, Silke J. The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia. Sci Transl Med. 2016 May 18;8(339):339ra69. doi: 10.1126/scitranslmed.aad3099. PubMed PMID: 27194727.

4: Elbekai RH, Paranjpe MG, Contreras PC, Spada A. Carcinogenicity assessment of the pan-caspase inhibitor, emricasan, in Tg.rasH2 mice. Regul Toxicol Pharmacol. 2015 Jul;72(2):169-78. doi: 10.1016/j.yrtph.2015.04.007. Epub 2015 Apr 17. PubMed PMID: 25896096.

5: Barreyro FJ, Holod S, Finocchietto PV, Camino AM, Aquino JB, Avagnina A, Carreras MC, Poderoso JJ, Gores GJ. The pan-caspase inhibitor Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis. Liver Int. 2015 Mar;35(3):953-66. doi: 10.1111/liv.12570. Epub 2014 Jun 6. PubMed PMID: 24750664.

6: Haddad JJ. Current opinion on 3-[2-[(2-tert-butyl-phenylaminooxalyl)-amino]-propionylamino]- 4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid, an investigational drug targeting caspases and caspase-like proteases: the clinical trials in sight and recent anti-inflammatory advances. Recent Pat Inflamm Allergy Drug Discov. 2013 Sep;7(3):229-58. Review. PubMed PMID: 23859695.

7: McCall MD, Maciver AM, Kin T, Emamaullee J, Pawlick R, Edgar R, Shapiro AM. Caspase inhibitor IDN6556 facilitates marginal mass islet engraftment in a porcine islet autotransplant model. Transplantation. 2012 Jul 15;94(1):30-5. doi: 10.1097/TP.0b013e318257745d. PubMed PMID: 22706322.

8: McCall M, Toso C, Emamaullee J, Pawlick R, Edgar R, Davis J, Maciver A, Kin T, Arch R, Shapiro AM. The caspase inhibitor IDN-6556 (PF3491390) improves marginal mass engraftment after islet transplantation in mice. Surgery. 2011 Jul;150(1):48-55. doi: 10.1016/j.surg.2011.02.023. Epub 2011 May 18. PubMed PMID: 21596412.

9: Shiffman ML, Pockros P, McHutchison JG, Schiff ER, Morris M, Burgess G. Clinical trial: the efficacy and safety of oral PF-03491390, a pancaspase inhibitor - a randomized placebo-controlled study in patients with chronic hepatitis C. Aliment Pharmacol Ther. 2010 May;31(9):969-78. doi: 10.1111/j.1365-2036.2010.04264.x. Epub 2010 Feb 16. PubMed PMID: 20163376.

10: Pockros PJ. Antifibrotics for chronic hepatitis C. Clin Liver Dis. 2009 Aug;13(3):365-73. doi: 10.1016/j.cld.2009.05.005. Review. PubMed PMID: 19628154.

11: Fischer U, Janssen K, Schulze-Osthoff K. Does caspase inhibition promote clonogenic tumor growth? Cell Cycle. 2007 Dec 15;6(24):3048-53. Epub 2007 Oct 2. Review. PubMed PMID: 18073530.

12: Ueno Y, Ohmi T, Yamamoto M, Kato N, Moriguchi Y, Kojima M, Shimozono R, Suzuki S, Matsuura T, Eda H. Orally-administered caspase inhibitor PF-03491390 is retained in the liver for prolonged periods with low systemic exposure, exerting a hepatoprotective effect against alpha-fas-induced liver injury in a mouse model. J Pharmacol Sci. 2007 Oct;105(2):201-5. Epub 2007 Oct 6. PubMed PMID: 17928737.

13: Pockros PJ, Schiff ER, Shiffman ML, McHutchison JG, Gish RG, Afdhal NH, Makhviladze M, Huyghe M, Hecht D, Oltersdorf T, Shapiro DA. Oral IDN-6556, an antiapoptotic caspase inhibitor, may lower aminotransferase activity in patients with chronic hepatitis C. Hepatology. 2007 Aug;46(2):324-9. PubMed PMID: 17654603.

14: Georgiev P, Clavien PA, Gores GJ. Liver graft protection by antiapoptotic drugs: a step further. Liver Transpl. 2007 Mar;13(3):318-20. PubMed PMID: 17318874.

15: Hoglen NC, Anselmo DM, Katori M, Kaldas M, Shen XD, Valentino KL, Lassman C, Busuttil RW, Kupiec-Weglinski JW, Farmer DG. A caspase inhibitor, IDN-6556, ameliorates early hepatic injury in an ex vivo rat model of warm and cold ischemia. Liver Transpl. 2007 Mar;13(3):361-6. PubMed PMID: 17318854.

16: Baskin-Bey ES, Washburn K, Feng S, Oltersdorf T, Shapiro D, Huyghe M, Burgart L, Garrity-Park M, van Vilsteren FG, Oliver LK, Rosen CB, Gores GJ. Clinical Trial of the Pan-Caspase Inhibitor, IDN-6556, in Human Liver Preservation Injury. Am J Transplant. 2007 Jan;7(1):218-25. PubMed PMID: 17227570.

17: Davis GL. New therapies: oral inhibitors and immune modulators. Clin Liver Dis. 2006 Nov;10(4):867-80. Review. PubMed PMID: 17164122.

18: Leung-Toung R, Zhao Y, Li W, Tam TF, Karimian K, Spino M. Thiol proteases: inhibitors and potential therapeutic targets. Curr Med Chem. 2006;13(5):547-81. Review. PubMed PMID: 16515521.

19: Linton SD, Aja T, Armstrong RA, Bai X, Chen LS, Chen N, Ching B, Contreras P, Diaz JL, Fisher CD, Fritz LC, Gladstone P, Groessl T, Gu X, Herrmann J, Hirakawa BP, Hoglen NC, Jahangiri KG, Kalish VJ, Karanewsky DS, Kodandapani L, Krebs J, McQuiston J, Meduna SP, Nalley K, Robinson ED, Sayers RO, Sebring K, Spada AP, Ternansky RJ, Tomaselli KJ, Ullman BR, Valentino KL, Weeks S, Winn D, Wu JC, Yeo P, Zhang CZ. First-in-class pan caspase inhibitor developed for the treatment of liver disease. J Med Chem. 2005 Nov 3;48(22):6779-82. PubMed PMID: 16250635.

20: Quadri SM, Segall L, de Perrot M, Han B, Edwards V, Jones N, Waddell TK, Liu M, Keshavjee S. Caspase inhibition improves ischemia-reperfusion injury after lung transplantation. Am J Transplant. 2005 Feb;5(2):292-9. PubMed PMID: 15643988.

Original: Obeticholic Acid 459789-99-2, stock more than 100g

EOS med chem is the only manufacturer that provides excellent quality chemistry products and services at affordable rates. The experts working here are highly trained to handle these chemicals used in the creation of medicines used for treating various life-threatening diseases. We are into the manufacturing of chemical products after doing a deep research for the same.

EOS team of experts holds the work experience of more than ten years, and therefore we can assure you about the quality and superiority of the products and services we offer to all our valued clients around the globe. At present, this organization is listed among the most leading pharmaceutical suppliers around the world. We always supply products keeping the affordability in mind.

2018 CHINA CPHI, W4E82

EOS Med Chem, Medchem is Big
執大象，天下往，往而無害，安平泰
WEB: www.eosmedchem.com
EMAIL: info@eosmedchem.com; eosmedchem@gmail.com; eosmedchem@qq.com  
TEL: 0086-531-69905422
GMP PLANT: No. 37, Yulong Road, Qufu City, Shandong Province.

Description: Obeticholic Acid (INT747; 6-ECDCA) is a novel derivative of cholic acid which acts as a potent and selective FXR agonist displaying anticholeretic activity in an in vivo rat model of cholestasis. It inhibits vascular smooth muscle cell inflammation and migration as well as promotes adipocyte differentiation and regulates adipose cell function in vivo.

Name: Obeticholic Acid 

CAS#: 459789-99-2 

Chemical Formula: C26H44O4 

Exact Mass: 420.32396 

Molecular Weight: 420.63 

Elemental Analysis: C, 74.24; H, 10.54; O, 15.21

Synonym: 6-Ethylchenodeoxycholic acid; Obeticholic acid; INT 747; INT-747; INT747; 6-ECDCA; Ocaliva.

IUPAC/Chemical Name: (4R)-4-[(3R,5S,6R,7R,8S,9S,10S,13R,14S,17R)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoic acid

InChi Key: ZXERDUOLZKYMJM-ZWECCWDJSA-N

InChi Code: InChI=1S/C26H44O4/c1-5-17-21-14-16(27)10-12-26(21,4)20-11-13-25(3)18(15(2)6-9-22(28)29)7-8-19(25)23(20)24(17)30/h15-21,23-24,27,30H,5-14H2,1-4H3,(H,28,29)/t15-,16-,17-,18-,19+,20+,21+,23+,24-,25-,26-/m1/s1

SMILES Code: C[C@@H]([C@H]1CC[C@@]2([H])[C@]3([H])[C@H](O)[C@H](CC)[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)CCC(O)=O

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code: 291819

REFERENCES

1: Armstrong MJ, Newsome PN. Trials of obeticholic acid for non-alcoholic steatohepatitis. Lancet. 2015 Jul 4;386(9988):28. doi: 10.1016/S0140-6736(15)61199-0. PubMed PMID: 26169862.

2: Neuschwander-Tetri BA, Van Natta ML, Tonascia J, Brunt EM, Kleiner DE. Trials of obeticholic acid for non-alcoholic steatohepatitis - Authors' reply. Lancet. 2015 Jul 4;386(9988):28-9. doi: 10.1016/S0140-6736(15)61200-4. PubMed PMID: 26169861.

3: Musso G, Cassader M, Gambino R. Trials of obeticholic acid for non-alcoholic steatohepatitis. Lancet. 2015 Jul 4;386(9988):27. doi: 10.1016/S0140-6736(15)61198-9. PubMed PMID: 26169860.

4: Dong R, Zheng S, Chen G. The Appropriate Timing and Dose of Obeticholic Acid in Patients With Primary Biliary Cirrhosis. Gastroenterology. 2015 Aug;149(2):508. doi: 10.1053/j.gastro.2015.01.050. Epub 2015 Jun 29. PubMed PMID: 26136168.

5: Arrese M, Cabrera D, Barrera F. Obeticholic acid: expanding the therapeutic landscape of NASH. Ann Hepatol. 2015 May-Jun;14(3):430-2. PubMed PMID: 25864227.

6: Musso G. Obeticholic acid and resveratrol in nonalcoholic fatty liver disease: all that is gold does not glitter, not all those who wander are lost. Hepatology. 2015 Jun;61(6):2104-6. doi: 10.1002/hep.27772. Epub 2015 Apr 8. PubMed PMID: 25753820.

7: Wong VW, Wong GL, Chan FK. Is obeticholic Acid the solution to nonalcoholic steatohepatitis? Gastroenterology. 2015 Apr;148(4):851-2. doi: 10.1053/j.gastro.2015.02.044. Epub 2015 Feb 26. PubMed PMID: 25726736.

8: Verbeke L, Farre R, Verbinnen B, Covens K, Vanuytsel T, Verhaegen J, Komuta M, Roskams T, Chatterjee S, Annaert P, Vander Elst I, Windmolders P, Trebicka J, Nevens F, Laleman W. The FXR agonist obeticholic acid prevents gut barrier dysfunction and bacterial translocation in cholestatic rats. Am J Pathol. 2015 Feb;185(2):409-19. doi: 10.1016/j.ajpath.2014.10.009. Epub 2015 Jan 12. PubMed PMID: 25592258.

9: Hirschfield GM, Mason A, Luketic V, Lindor K, Gordon SC, Mayo M, Kowdley KV, Vincent C, Bodhenheimer HC Jr, Parés A, Trauner M, Marschall HU, Adorini L, Sciacca C, Beecher-Jones T, Castelloe E, Böhm O, Shapiro D. Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid. Gastroenterology. 2015 Apr;148(4):751-61.e8. doi: 10.1053/j.gastro.2014.12.005. Epub 2014 Dec 11. PubMed PMID: 25500425.

10: Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, Chalasani N, Dasarathy S, Diehl AM, Hameed B, Kowdley KV, McCullough A, Terrault N, Clark JM, Tonascia J, Brunt EM, Kleiner DE, Doo E; NASH Clinical Research Network. Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. Lancet. 2015 Mar 14;385(9972):956-65. doi: 10.1016/S0140-6736(14)61933-4. Epub 2014 Nov 7. Erratum in: Lancet. 2015 Mar 14;385(9972):946. PubMed PMID: 25468160; PubMed Central PMCID: PMC4447192.

Original: CPI203 1446144-04-2 , stock more than 100g

EOS med chem is the only manufacturer that provides excellent quality chemistry products and services at affordable rates. The experts working here are highly trained to handle these chemicals used in the creation of medicines used for treating various life-threatening diseases. We are into the manufacturing of chemical products after doing a deep research for the same.

EOS team of experts holds the work experience of more than ten years, and therefore we can assure you about the quality and superiority of the products and services we offer to all our valued clients around the globe. At present, this organization is listed among the most leading pharmaceutical suppliers around the world. We always supply products keeping the affordability in mind.

2018 CHINA CPHI, W4E82

EOS Med Chem, Medchem is Big
執大象，天下往，往而無害，安平泰
WEB: www.eosmedchem.com
EMAIL: info@eosmedchem.com; eosmedchem@gmail.com; eosmedchem@qq.com  
TEL: 0086-531-69905422
GMP PLANT: No. 37, Yulong Road, Qufu City, Shandong Province.

Description: CPI203, also known as TEN010, JQ-2 and RG6146, is a potent and orally active BET bromodomain inhibitor. CPI203 enhances the antiproliferative effects of rapamycin on human neuroendocrine tumors. CPI203 ownregulates Myc expression, causes G1 cell cycle arrest and attenuates cell proliferation in human pancreatic neuroendocrine tumors. CPI203 arrests the growth of T cell acute lymphoblastic leukemia cells in vitro (EC50 = 91.2 nM).

Name: CPI203 

CAS#: 1446144-04-2 

Chemical Formula: C19H18ClN5OS 

Exact Mass: 399.09206 

Molecular Weight: 399.9 

Elemental Analysis: C, 57.07; H, 4.54; Cl, 8.86; N, 17.51; O, 4.00; S, 8.02

Synonym: CPI203; CPI-203; CPI 203; TEN010; TEN 010; TEN010; JQ-2; JQ 2; JQ2; RG-6146; RG 6146; RG-6146.

IUPAC/Chemical Name: (S)-2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetamide

InChi Key: QECMENZMDBOLDR-AWEZNQCLSA-N

InChi Code: InChI=1S/C19H18ClN5OS/c1-9-10(2)27-19-16(9)17(12-4-6-13(20)7-5-12)22-14(8-15(21)26)18-24-23-11(3)25(18)19/h4-7,14H,8H2,1-3H3,(H2,21,26)/t14-/m0/s1

SMILES Code: O=C(N)C[C@H]1C2=NN=C(C)N2C3=C(C(C)=C(C)S3)C(C4=CC=C(Cl)C=C4)=N1

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code: 293490

ADDITIONAL INFORMATION

TEN-010 binds to the acetylated lysine recognition motifs found in the bromodomain of BET proteins, which prevents the interaction between BET proteins and acetylated histones. This interaction disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to an inhibition of tumor cell growth.

REFERENCES

1: Wong C, Laddha SV, Tang L, Vosburgh E, Levine AJ, Normant E, Sandy P, Harris CR, Chan CS, Xu EY. The bromodomain and extra-terminal inhibitor CPI203 enhances the antiproliferative effects of rapamycin on human neuroendocrine tumors. Cell Death Dis. 2014 Oct 9;5:e1450. doi: 10.1038/cddis.2014.396. PubMed PMID: 25299775; PubMed Central PMCID: PMC4237236.

2: Moros A, Rodríguez V, Saborit-Villarroya I, Montraveta A, Balsas P, Sandy P, Martínez A, Wiestner A, Normant E, Campo E, Pérez-Galán P, Colomer D, Roué G. Synergistic antitumor activity of lenalidomide with the BET bromodomain inhibitor CPI203 in bortezomib-resistant mantle cell lymphoma. Leukemia. 2014 Oct;28(10):2049-59. doi: 10.1038/leu.2014.106. Epub 2014 Mar 18. PubMed PMID: 24721791.

Original: Epacadostat 1204669-58-8 , stock more than 100g

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Description: Epacadostat, also known as INCB024360 or INCB24360, is an orally available hydroxyamidine and inhibitor of indoleamine 2,3-dioxygenase (IDO1), with potential immunomodulating and antineoplastic activities. INCB024360 targets and binds to IDO1, an enzyme responsible for the oxidation of tryptophan into kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, INCB024360 increases and restores the proliferation and activation of various immune cells, including dendritic cells (DCs), NK cells, and T-lymphocytes, as well as interferon (IFN) production, and a reduction in tumor-associated regulatory T cells (Tregs).

Name: Epacadostat (INCB024360) 

CAS#: 1204669-58-8 (INCB024360) 

Chemical Formula: C11H13BrFN7O4S 

Exact Mass: 436.99171 

Molecular Weight: 438.23 

Elemental Analysis: C, 30.15; H, 2.99; Br, 18.23; F, 4.34; N, 22.37; O, 14.60; S, 7.32

Related CAS #: 1204669-58-8 (INCB024360)   1204669-37-3 (INCB024360)   914471-09-3 (INCB024360-analog)    

Synonym: INCB024360; INCB 024360; INCB-024360; INCB24360; INCB-24360; INCB 24360; Epacadostat

IUPAC/Chemical Name: (Z)-N-(3-bromo-4-fluorophenyl)-N'-hydroxy-4-((2-(sulfamoylamino)ethyl)amino)-1,2,5-oxadiazole-3-carboximidamide

InChi Key: FBKMWOJEPMPVTQ-UHFFFAOYSA-N

InChi Code: InChI=1S/C11H13BrFN7O4S/c12-7-5-6(1-2-8(7)13)17-11(18-21)9-10(20-24-19-9)15-3-4-16-25(14,22)23/h1-2,5,16,21H,3-4H2,(H,15,20)(H,17,18)(H2,14,22,23)

SMILES Code: O=S(NCCNC1=NON=C1/C(NC2=CC=C(F)C(Br)=C2)=N/O)(N)=O

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO, DMA, etc. Method 1: INCB024360 was reconstituted in 5% DMA, 47.5% propylene glycol. (See J. Med. Chem, 2009, 52(23), 7364. supporting information). Methdod 2: INCB024360 was reconstituted in 3% DMA, 10% (2-Hydroxypropyl) β-Cyclodextrin. (see: Mol. Cancer. Ther. 2010, 9(2), 489. ). Note: DMA = N,N–Dimethylacetamide.

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code: 293490

ADDITIONAL INFORMATION

Related CAS#: 

INCB024360: CAS#1204669-58-8 (or 1204669-37-3) 

INCB024360-analog: CAS#914471-09-3 

REFERENCES

1: Yue EW, Sparks R, Polam P, Modi D, Douty B, Wayland B, Glass B, Takvorian A, Glenn J, Zhu W, Bower M, Liu X, Leffet L, Wang Q, Bowman KJ, Hansbury MJ, Wei M, Li Y, Wynn R, Burn TC, Koblish HK, Fridman JS, Emm T, Scherle PA, Metcalf B, Combs AP. INCB24360 (Epacadostat), a Highly Potent and Selective Indoleamine-2,3-dioxygenase 1 (IDO1) Inhibitor for Immuno-oncology. ACS Med Chem Lett. 2017 Mar 6;8(5):486-491. doi: 10.1021/acsmedchemlett.6b00391. eCollection 2017 May 11. PubMed PMID: 28523098; PubMed Central PMCID: PMC5430407.

2: Wu Y, Xu T, Liu J, Ding K, Xu J. Structural insights into the binding mechanism of IDO1 with hydroxylamidine based inhibitor INCB14943. Biochem Biophys Res Commun. 2017 May 27;487(2):339-343. doi: 10.1016/j.bbrc.2017.04.061. Epub 2017 Apr 13. PubMed PMID: 28412361.

3: Maliniemi P, Laukkanen K, Väkevä L, Dettmer K, Lipsanen T, Jeskanen L, Bessede A, Oefner PJ, Kadin ME, Ranki A. Biological and clinical significance of tryptophan-catabolizing enzymes in cutaneous T-cell lymphomas. Oncoimmunology. 2017 Feb 10;6(3):e1273310. doi: 10.1080/2162402X.2016.1273310. eCollection 2017. PubMed PMID: 28405495; PubMed Central PMCID: PMC5384345.

4: Brochez L, Chevolet I, Kruse V. The rationale of indoleamine 2,3-dioxygenase inhibition for cancer therapy. Eur J Cancer. 2017 May;76:167-182. doi: 10.1016/j.ejca.2017.01.011. Epub 2017 Mar 18. Review. PubMed PMID: 28324751.

5: Zhang Q, Zhang Y, Boer J, Shi JG, Hu P, Diamond S, Yeleswaram S. In Vitro Interactions of Epacadostat and its Major Metabolites with Human Efflux and Uptake Transporters: Implications for Pharmacokinetics and Drug Interactions. Drug Metab Dispos. 2017 Jun;45(6):612-623. doi: 10.1124/dmd.116.074609. Epub 2017 Mar 10. PubMed PMID: 28283500.

6: Beatty GL, O'Dwyer PJ, Clark J, Shi JG, Bowman KJ, Scherle PA, Newton RC, Schaub R, Maleski J, Leopold L, Gajewski TF. First-in-Human Phase I Study of the Oral Inhibitor of Indoleamine 2,3-Dioxygenase-1 Epacadostat (INCB024360) in Patients with Advanced Solid Malignancies. Clin Cancer Res. 2017 Jan 4. doi: 10.1158/1078-0432.CCR-16-2272. [Epub ahead of print] PubMed PMID: 28053021.

7: Shi JG, Bowman KJ, Chen X, Maleski J, Leopold L, Yeleswaram S. Population Pharmacokinetic and Pharmacodynamic Modeling of Epacadostat in Patients With Advanced Solid Malignancies. J Clin Pharmacol. 2017 Jun;57(6):720-729. doi: 10.1002/jcph.855. Epub 2016 Dec 19. PubMed PMID: 27990653.

8: Jochems C, Fantini M, Fernando RI, Kwilas AR, Donahue RN, Lepone LM, Grenga I, Kim YS, Brechbiel MW, Gulley JL, Madan RA, Heery CR, Hodge JW, Newton R, Schlom J, Tsang KY. The IDO1 selective inhibitor epacadostat enhances dendritic cell immunogenicity and lytic ability of tumor antigen-specific T cells. Oncotarget. 2016 Jun 21;7(25):37762-37772. doi: 10.18632/oncotarget.9326. PubMed PMID: 27192116; PubMed Central PMCID: PMC5122347.

9: Boer J, Young-Sciame R, Lee F, Bowman KJ, Yang X, Shi JG, Nedza FM, Frietze W, Galya L, Combs AP, Yeleswaram S, Diamond S. Roles of UGT, P450, and Gut Microbiota in the Metabolism of Epacadostat in Humans. Drug Metab Dispos. 2016 Oct;44(10):1668-74. doi: 10.1124/dmd.116.070680. Epub 2016 Jul 25. PubMed PMID: 27457784.

10: Dhiman V, Giri KK, S SP, Zainuddin M, Rajagopal S, Mullangi R. Determination of epacadostat, a novel IDO1 inhibitor in mouse plasma by LC-MS/MS and its application to a pharmacokinetic study in mice. Biomed Chromatogr. 2017 Feb;31(2). doi: 10.1002/bmc.3794. Epub 2016 Aug 11. PubMed PMID: 27451018.

11: Shi JG, Chen X, Punwani NG, Williams WV, Yeleswaram S. Potential Underprediction of Warfarin Drug Interaction From Conventional Interaction Studies and Risk Mitigation: A Case Study With Epacadostat, an IDO1 Inhibitor. J Clin Pharmacol. 2016 Nov;56(11):1344-1354. doi: 10.1002/jcph.737. PubMed PMID: 26990117.

12: Zhai L, Spranger S, Binder DC, Gritsina G, Lauing KL, Giles FJ, Wainwright DA. Molecular Pathways: Targeting IDO1 and Other Tryptophan Dioxygenases for Cancer Immunotherapy. Clin Cancer Res. 2015 Dec 15;21(24):5427-33. doi: 10.1158/1078-0432.CCR-15-0420. Epub 2015 Oct 30. Review. PubMed PMID: 26519060; PubMed Central PMCID: PMC4681601.

13: Vacchelli E, Aranda F, Eggermont A, Sautès-Fridman C, Tartour E, Kennedy EP, Platten M, Zitvogel L, Kroemer G, Galluzzi L. Trial watch: IDO inhibitors in cancer therapy. Oncoimmunology. 2014 Dec 15;3(10):e957994. eCollection 2014 Nov. Review. PubMed PMID: 25941578; PubMed Central PMCID: PMC4292223.

14: Liu X, Shin N, Koblish HK, Yang G, Wang Q, Wang K, Leffet L, Hansbury MJ, Thomas B, Rupar M, Waeltz P, Bowman KJ, Polam P, Sparks RB, Yue EW, Li Y, Wynn R, Fridman JS, Burn TC, Combs AP, Newton RC, Scherle PA. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood. 2010 Apr 29;115(17):3520-30. doi: 10.1182/blood-2009-09-246124. Epub 2010 Mar 2. PubMed PMID: 20197554.

15: Koblish HK, Hansbury MJ, Bowman KJ, Yang G, Neilan CL, Haley PJ, Burn TC, Waeltz P, Sparks RB, Yue EW, Combs AP, Scherle PA, Vaddi K, Fridman JS. Hydroxyamidine inhibitors of indoleamine-2,3-dioxygenase potently suppress systemic tryptophan catabolism and the growth of IDO-expressing tumors. Mol Cancer Ther. 2010 Feb;9(2):489-98. doi: 10.1158/1535-7163.MCT-09-0628. Epub 2010 Feb 2. PubMed PMID: 20124451.