The marketing of obeticholic acid (OCA) in the United States and Europe has been the pinnacle of a research program initiated by Roberto Pellicciari and his group at the University of Perugia in 1982. The first scientific publication on OCA as a potent and selective farnesoid X receptor (FXR) bile acid (BA) agonist was in the Journal of Medicinal Chemistry in 2002. OCA is evaluated in clinical trials for nonalcoholic steatohepatitis (NASH), and primary sclerosing cholangitis (PSC). This chapter is structured to provide the reader with a historical account and rationale behind the discovery of OCA. It starts with an overview of the structural and physicochemical properties of bile acids (BAs) and their physiological roles and therapeutic applications. The importance of the contiguous hydrophobic area in BA aggregation is clearly evidenced by critical micellar concentration (CMC) values assessed for endogenous BAs such as chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA).
The Discovery of Obeticholic Acid (Ocaliva™): First‐in‐Class FXR Agonist
Roberto Pellicciari;Antimo Gioiello
2018
Abstract
The marketing of obeticholic acid (OCA) in the United States and Europe has been the pinnacle of a research program initiated by Roberto Pellicciari and his group at the University of Perugia in 1982. The first scientific publication on OCA as a potent and selective farnesoid X receptor (FXR) bile acid (BA) agonist was in the Journal of Medicinal Chemistry in 2002. OCA is evaluated in clinical trials for nonalcoholic steatohepatitis (NASH), and primary sclerosing cholangitis (PSC). This chapter is structured to provide the reader with a historical account and rationale behind the discovery of OCA. It starts with an overview of the structural and physicochemical properties of bile acids (BAs) and their physiological roles and therapeutic applications. The importance of the contiguous hydrophobic area in BA aggregation is clearly evidenced by critical micellar concentration (CMC) values assessed for endogenous BAs such as chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA).I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
