Emricasan

Emricasan
Legal status
Legal status	US: 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;
CompTox Dashboard (EPA)	DTXSID10180160 ;
Chemical and physical data
Formula	C26H27F4N3O7
Molar mass	569.501 g·mol−1
3D model (JSmol)	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 potential drug invented in 1998 by Idun Pharmaceuticals.^[1]^[2] The drug was acquired by Pfizer in 2005^[3] and then sold to Conatus Pharmaceuticals in 2010.^[1] Conatus in turn licensed emricasan to Novartis in 2017 for exclusive development and commercialization.^[4]

The substance acts as a pan-caspase inhibitor and has antiapoptotic and antiinflammatory effects.^[4] It was developed for the treatment of liver disease^[5] and has been granted fast track designation by the FDA for the treatment of non-alcoholic steatohepatitis cirrhosis^[6]^[7]^[8] The substance is the first pan-caspase inhibitor to advance to broad clinical testing, and its novel mechanism of action has led to research using it for other potential applications.^[9]^[10]

References

^ ^a ^b McCallister E (Aug 9, 2010). "IDUN IT AGAIN: Conatus Reacquires Idun Assets From Pfizer, Hopes Data Will Attract Investors". BioCentury.
^ Linton SD, Aja T, Armstrong RA, Bai X, Chen LS, Chen N, et al. (November 2005). "First-in-class pan caspase inhibitor developed for the treatment of liver disease". Journal of Medicinal Chemistry. 48 (22): 6779–82. doi:10.1021/jm050307e. PMID 16250635.
^ "Pfizer to acquire Idun Pharmaceuticals in cash transaction". Scrip. May 2005.
^ ^a ^b Taylor P (May 4, 2017). "Novartis adds to NASH pipeline, activating license for Conatus' emricasan". FierceBiotech.
^ Hoglen NC, Chen LS, Fisher CD, Hirakawa BP, Groessl T, Contreras PC (May 2004). "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". The Journal of Pharmacology and Experimental Therapeutics. 309 (2): 634–40. doi:10.1124/jpet.103.062034. PMID 14742742.
^ Marriott N (10 May 2017). "Lonza NEWS Novartis enter agreement with Conatus for NASH treatment". European Pharmaceutical Review.
^ Haddad JJ (September 2013). "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 Patents on Inflammation & Allergy Drug Discovery. 7 (3): 229–58. doi:10.2174/1872213X113079990017. PMID 23859695.
^ Rotman Y, Sanyal AJ (January 2017). "Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease". Gut. 66 (1): 180–190. doi:10.1136/gutjnl-2016-312431. PMID 27646933. S2CID 3461795.
^ Brumatti G, Ma C, Lalaoui N, Nguyen NY, Navarro M, Tanzer MC, et al. (May 2016). "The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia". Science Translational Medicine. 8 (339): 339ra69. doi:10.1126/scitranslmed.aad3099. PMID 27194727.
^ Xu M, Lee EM, Wen Z, Cheng Y, Huang WK, Qian X, et al. (October 2016). "Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen". Nature Medicine. 22 (10): 1101–1107. doi:10.1038/nm.4184. PMC 5386783. PMID 27571349.

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[BioCentury-1] McCallister E (Aug 9, 2010). "IDUN IT AGAIN: Conatus Reacquires Idun Assets From Pfizer, Hopes Data Will Attract Investors". BioCentury.

[J_med_Chem-2] Linton SD, Aja T, Armstrong RA, Bai X, Chen LS, Chen N, et al. (November 2005). "First-in-class pan caspase inhibitor developed for the treatment of liver disease". Journal of Medicinal Chemistry. 48 (22): 6779–82. doi:10.1021/jm050307e. PMID 16250635.

[3] "Pfizer to acquire Idun Pharmaceuticals in cash transaction". Scrip. May 2005.

[Fierce-4] Taylor P (May 4, 2017). "Novartis adds to NASH pipeline, activating license for Conatus' emricasan". FierceBiotech.

[pmid14742742-5] Hoglen NC, Chen LS, Fisher CD, Hirakawa BP, Groessl T, Contreras PC (May 2004). "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". The Journal of Pharmacology and Experimental Therapeutics. 309 (2): 634–40. doi:10.1124/jpet.103.062034. PMID 14742742.

[EPR-6] Marriott N (10 May 2017). "Lonza NEWS Novartis enter agreement with Conatus for NASH treatment". European Pharmaceutical Review.

[pmid23859695-7] Haddad JJ (September 2013). "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 Patents on Inflammation & Allergy Drug Discovery. 7 (3): 229–58. doi:10.2174/1872213X113079990017. PMID 23859695.

[pmid27646933-8] Rotman Y, Sanyal AJ (January 2017). "Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease". Gut. 66 (1): 180–190. doi:10.1136/gutjnl-2016-312431. PMID 27646933. S2CID 3461795.

[pmid27194727-9] Brumatti G, Ma C, Lalaoui N, Nguyen NY, Navarro M, Tanzer MC, et al. (May 2016). "The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia". Science Translational Medicine. 8 (339): 339ra69. doi:10.1126/scitranslmed.aad3099. PMID 27194727.

[pmid27571349-10] Xu M, Lee EM, Wen Z, Cheng Y, Huang WK, Qian X, et al. (October 2016). "Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen". Nature Medicine. 22 (10): 1101–1107. doi:10.1038/nm.4184. PMC 5386783. PMID 27571349.

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