Emricasan

Emricasan

Clinical data
Trade names	Emricasan
Legal status
Legal status	Investigational New Drug
Identifiers
IUPAC name (3S)-3-{[(2S)-2-{[2-(2-tert-butylanilino)-2-oxoacetyl]amino}propanoyl]amino}-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid
CAS Number	254750-02-2
PubChem (CID)	12000240
ChemSpider	10172707
UNII	P0GMS9N47Q
KEGG	D10004
Chemical and physical data
Formula	C26H27F4N3O7
Molar mass	569.501
3D model (Jmol)	Interactive image
SMILES C[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)COc1c(c(cc(c1F)F)F)F)NC(=O)C(=O)Nc2ccccc2C(C)(C)C
InChI 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 Key:SCVHJVCATBPIHN-SJCJKPOMSA-N

Emricasan (IDN-6556, PF-03491390) is a drug originally invented by Pfizer and licensed for development to Conatus Pharmaceuticals, which acts as a caspase inhibitor and has antiinflammatory effects. It was developed for the treatment of liver disease,^[1] and has been granted fast track designation by the FDA for development after positive results in Phase II clinical trials for non-alcoholic fatty liver disease.^[2][3] Emricasan is the first caspase inhibitor developed for clinical use, and this novel mechanism of action has led to interest in research using emricasan for other potential applications such as an anti-cancer or antiviral drug.^[4][5]

References

1. Hoglen NC, Chen LS, Fisher CD, Hirakawa BP, Groessl T, Contreras PC. Characterization of IDN-6556 (3-[2-(2-tert-butyl-phenylaminooxalyl)-amino]-propionylamino]-4-oxo-5-(2,3,5,6-tetrafluoro-phenoxy)-pentanoic acid): a liver-targeted caspase inhibitor. J Pharmacol Exp Ther. 2004 May;309(2):634-40. PMID 14742742
2. 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. PMID 23859695
3. 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. PMID 27646933
4. 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. PMID 27194727
5. 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. PMID 27571349