fasiglifam   Click here for help

GtoPdb Ligand ID: 6484

Synonyms: TAK 875 | TAK-875 | TAK875
PDB Ligand
Compound class: Synthetic organic
Comment: Fasiglifam is a positive allosteric modulator/partial agonist of the free fatty acid receptor 1 (FFA1, a.k.a. GPR40) [6]. In the presence of endogenous free fatty acids (FFAs) fasiglifam enhances insulin secretion, by binding to an allosteric site distinct from the orthosteric FFA binding site. On its own, it elicits a low level of insulin secretion. These findings indicate that fasiglifam acts cooperatively with FFAs to promote insulin secretion.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 11
Topological polar surface area 107.51
Molecular weight 524.19
XLogP 5.72
No. Lipinski's rules broken 2
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Canonical SMILES OC(=O)CC1COc2c1ccc(c2)OCc1cccc(c1)c1c(C)cc(cc1C)OCCCS(=O)(=O)C
Isomeric SMILES OC(=O)C[C@@H]1COc2c1ccc(c2)OCc1cccc(c1)c1c(C)cc(cc1C)OCCCS(=O)(=O)C
InChI InChI=1S/C29H32O7S/c1-19-12-25(34-10-5-11-37(3,32)33)13-20(2)29(19)22-7-4-6-21(14-22)17-35-24-8-9-26-23(15-28(30)31)18-36-27(26)16-24/h4,6-9,12-14,16,23H,5,10-11,15,17-18H2,1-3H3,(H,30,31)/t23-/m1/s1
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Summary of Clinical Use Click here for help
Fasiglifam has been in clinical trial as an antidiabetic drug. However, the News in Brief section of Nature Reviews Drug Discovery (Vol 13, p91 (2014), doi:10.1038/nrd4246) reports termination of a Phase 3 trial of fasiglifam due to unacceptable levels of liver toxicity. Click here to view the Clinicaltrials.gov record for this trial.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Fasiglifam is a GPR40 agonist. GPR40 is a candidate anti-diabetes drug target as it has been shown that agonists of this GPCR modulate insulin secretion from pancreatic β cells [1].