Discovery of 6alpha-Ethyl-23(S)-methylcholic Acid (S-EMCA, INT-777) as a Potent and Selective Agonist for the TGR5 Receptor, a Novel Target for Diabesity

Pellicciari, RobertoGioiello, AntimoMacchiarulo, AntonioThomas, CharlesRosatelli, EmilianoNatalini, BenedettoSardella, RoccaldoPruzanski, MarkRoda, AldoPastorini, ElisabettaSchoonjans, KristinaAuwerx, Johan2009-12-222009-12-222009-12-22200910.1021/jm901390phttps://infoscience.epfl.ch/handle/20.500.14299/44909WOS:000272712100010In the framework of the design and development of TGR5 agonists, we reported that the introduction of a C(23)(S)-methyl group in the side chain of bile acids such as chenodeoxycholic acid (CDCA) and 6-ethylchenodeoxycholic acid (6-ECDCA, INT-747) affords selectivity for TGR5. Herein we report further lead optimization efforts that have led to the discovery of 6alpha-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a novel potent and selective TGR5 agonist with remarkable in vivo activity.Farnesoid-X-ReceptorBile-AcidsNuclear ReceptorBiological-PropertiesDerivativesLigandsBindingFxrIdentificationSecretionDiscovery of 6alpha-Ethyl-23(S)-methylcholic Acid (S-EMCA, INT-777) as a Potent and Selective Agonist for the TGR5 Receptor, a Novel Target for Diabesitytext::journal::journal article::research article