firsocostat   Click here for help

GtoPdb Ligand ID: 10645

Synonyms: GS-0976 | GS-ACC | ND 630 [4] | ND-630 | NDI-010976
Compound class: Synthetic organic
Comment: Firsocostat (GS-0976) is a liver-directed acetyl-CoA carboxylase (ACC) inhibitor [2]. It was initially identified by Nimbus Therapeutics [3], and is being developed by Gilead as an antilipemic agent for potential to treat non-alcoholic steatohepatitis (NASH) [1]. Firsocostat is an allosteric inhibitor that binds to the ACC biotin carboxylase dimerization site, rather than to the previously targeted carboxyltransferase domain. The firsocostat-ACC interaction mimics the physiological inhibition of ACC by AMPK.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 9
Topological polar surface area 163.26
Molecular weight 569.18
XLogP 3.12
No. Lipinski's rules broken 0
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Canonical SMILES COc1ccccc1[C@H](Cn1c(=O)n(c(=O)c2c1sc(c2C)c1ncco1)C(C(=O)O)(C)C)OC1CCOCC1
Isomeric SMILES COc1ccccc1[C@H](Cn1c(=O)n(c(=O)c2c1sc(c2C)c1ncco1)C(C(=O)O)(C)C)OC1CCOCC1
InChI InChI=1S/C28H31N3O8S/c1-16-21-24(32)31(28(2,3)26(33)34)27(35)30(25(21)40-22(16)23-29-11-14-38-23)15-20(39-17-9-12-37-13-10-17)18-7-5-6-8-19(18)36-4/h5-8,11,14,17,20H,9-10,12-13,15H2,1-4H3,(H,33,34)/t20-/m0/s1
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Summary of Clinical Use Click here for help
GS-0976 has progressed to Phase 2 evaluation in patients with NASH. Its clinical efficacy has been compared to fenofibrate (PPARα agonist, antilipemic drug) and it is also being tested in combination with anti-fibrotic agents and other antilipemic agents. Click here to link to's full list of GS-0976 studies.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT00014690 ZD9331 With or Without Topotecan in Treating Patients With Refractory or Recurrent Epithelial Ovarian Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer Phase 2 Interventional National Cancer Institute (NCI)
NCT02891408 Pharmacokinetics of Firsocostat or Fenofibrate in Adults With Normal and Impaired Hepatic Function Phase 1 Interventional Gilead Sciences
NCT02856555 Study to Evaluate Safety, Tolerability, and Efficacy of GS-0976 in Adults With Nonalcoholic Steatohepatitis Phase 2 Interventional Gilead Sciences 5