Fasiglifam

Fasiglifam is an ago-allosteric modulator of  free fatty acid receptor 1 (FFAR1(GPR40)), which amplifies the agonistic activity of the endogenous ligand c-linolenic acid (c-LA) by binding to an allosteric site of FFAR1. Fasiglifam alone exhibited partial agonistic activity in cells expressing moderate levels of FFAR1, and exerted positive cooperative effects with free fatty acids (FFAs) in vitro and in vivo. Fasiglifam displays excellent potency and selectivity for FFAR1 (EC50=14nM) over other members of the FFA receptor family (GPR41, GPR43, GPR120, for which EC50>10 μM). Partial agonistic activity of Fasiglifam as determined by intracellular calcium mobilization assays in CHO cells is dependent upon FFAR1 gene expression levels and augmentation of glucose-induced insulin secretion by fasiglifam, c-LA, or their combination was completely abolished in pancreatic islets of FFAR1-knockout mice (doi:10.1371/journal.pone.0076280) providing additional evidence for selectivity. Fasiglifam advanced into the clinic but was terminated due to idiosyncratic liver toxicity.

1. Compound not tested for x-reactivity outside the FAR-family. 
2. The  liver safety aspect has been mechanistically investigated in   https://pubmed.ncbi.nlm.nih.gov/30243991/   and  https://pubmed.ncbi.nlm.nih.gov/28206647/
3. Primary Takeda patent filing with initial SAR is probably  US20120046338 – Fused cyclic compounds