clesacostat   Click here for help

GtoPdb Ligand ID: 12242

Synonyms: PF-05221304 | PF05221304
Compound class: Synthetic organic
Comment: Clesacostat (PF-05221304) is an acetyl-CoA carboxylase (ACC) inhibitor [3]. It was designed to treat non-alcoholic steatohepatitis (NASH) by targeting disordered lipid metabolism in the liver.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 1
Rotatable bonds 6
Topological polar surface area 114.62
Molecular weight 502.56
XLogP 4.38
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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Canonical SMILES COc1cc(cc(n1)c1ccc(cc1)C(=O)O)C(=O)N1CCC2(CC1)CC(=O)c1c(C2)cnn1C(C)C
Isomeric SMILES CC(C)n1c2c(CC3(CCN(CC3)C(=O)c3cc(nc(c3)OC)c3ccc(cc3)C(=O)O)CC2=O)cn1
InChI InChI=1S/C28H30N4O5/c1-17(2)32-25-21(16-29-32)14-28(15-23(25)33)8-10-31(11-9-28)26(34)20-12-22(30-24(13-20)37-3)18-4-6-19(7-5-18)27(35)36/h4-7,12-13,16-17H,8-11,14-15H2,1-3H3,(H,35,36)
InChI Key LXZMHBHEXAELHH-UHFFFAOYSA-N
References
1. Amin NB, Darekar A, Anstee QM, Wong VW, Tacke F, Vourvahis M, Lee DS, Charlton M, Alkhouri N, Nakajima A et al.. (2022)
Efficacy and safety of an orally administered DGAT2 inhibitor alone or coadministered with a liver-targeted ACC inhibitor in adults with non-alcoholic steatohepatitis (NASH): rationale and design of the phase II, dose-ranging, dose-finding, randomised, placebo-controlled MIRNA (Metabolic Interventions to Resolve NASH with fibrosis) study.
BMJ Open, 12 (3): e056159. [PMID:35354614]
2. Calle RA, Amin NB, Carvajal-Gonzalez S, Ross TT, Bergman A, Aggarwal S, Crowley C, Rinaldi A, Mancuso J, Aggarwal N et al.. (2021)
ACC inhibitor alone or co-administered with a DGAT2 inhibitor in patients with non-alcoholic fatty liver disease: two parallel, placebo-controlled, randomized phase 2a trials.
Nat Med, 27 (10): 1836-1848. [PMID:34635855]
3. Huard K, Smith AC, Cappon G, Dow RL, Edmonds DJ, El-Kattan A, Esler WP, Fernando DP, Griffith DA, Kalgutkar AS et al.. (2020)
Optimizing the Benefit/Risk of Acetyl-CoA Carboxylase Inhibitors through Liver Targeting.
J Med Chem, 63 (19): 10879-10896. [PMID:32809824]