Emricasan Explained

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. 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. 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]}

Notes and References

1. News: McCallister. Erin. vanc . IDUN IT AGAIN: Conatus Reacquires Idun Assets From Pfizer, Hopes Data Will Attract Investors . BioCentury . Aug 9, 2010 .
2. 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 . 6 . First-in-class pan caspase inhibitor developed for the treatment of liver disease . Journal of Medicinal Chemistry . 48 . 22 . 6779–82 . November 2005 . 16250635 . 10.1021/jm050307e .
3. News: Pfizer to acquire Idun Pharmaceuticals in cash transaction . Scrip. May 2005.
4. News: Taylor. Phil . vanc . Novartis adds to NASH pipeline, activating license for Conatus' emricasan. FierceBiotech. May 4, 2017.
5. 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 . The Journal of Pharmacology and Experimental Therapeutics . 309 . 2 . 634–40 . May 2004 . 14742742 . 10.1124/jpet.103.062034 .
6. News: Marriott. Niamh . vanc . Lonza NEWS Novartis enter agreement with Conatus for NASH treatment . European Pharmaceutical Review. 10 May 2017.
7. 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 Patents on Inflammation & Allergy Drug Discovery . 7 . 3 . 229–58 . September 2013 . 23859695 . 10.2174/1872213X113079990017 .
8. Rotman Y, Sanyal AJ . Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease . Gut . 66 . 1 . 180–190 . January 2017 . 27646933 . 10.1136/gutjnl-2016-312431 . 3461795 . free .
9. 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 . 6 . 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 . May 2016 . 27194727 . 10.1126/scitranslmed.aad3099 . free .
10. 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 . 6 . 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 . October 2016 . 27571349 . 5386783 . 10.1038/nm.4184 .