Tropifexor Clinical data ATC code Identifiers
2-[(1 R,5 S)-3-[[5-Cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl]methoxy]-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid CAS Number PubChem CID UNII KEGG Chemical and physical data Formula C 29 H 25 F 4 N 3 O 5 S Molar mass g·mol 603.59 −1 3D model ( JSmol)
Tropifexor is an investigational drug which acts as an agonist of the farnesoid X receptor (FXR). It was discovered by researchers from Novartis and Genomics Institute of the Novartis Research Foundation. Its synthesis and pharmacological properties were published in 2017. It was developed for the treatment of  cholestatic liver diseases and nonalcoholic steatohepatitis (NASH). In combination with cenicriviroc, a CCR2 and CCR5 receptor inhibitor, it is undergoing a phase II clinical trial for NASH and liver fibrosis.
Rats treated orally with tropifexor (0.03 to 1 mg/kg) showed an upregulation of the FXR target genes, BSEP and SHP, and a down-regulation of CYP8B1. Its EC50 for FXR is between 0.2 and 0.26 nM depending on the biochemical assay.
The patent which covers tropifexor and related compounds was published in 2010.
References [ edit ]
Tully, David C.; Rucker, Paul V.; Chianelli, Donatella; Williams, Jennifer; Vidal, Agnès; Alper, Phil B.; Mutnick, Daniel; Bursulaya, Badry; Schmeits, James; Wu, Xiangdong; Bao, Dingjiu; Zoll, Jocelyn; Kim, Young; Groessl, Todd; McNamara, Peter; Seidel, H. Martin; Molteni, Valentina; Liu, Bo; Phimister, Andrew; Joseph, Sean B.; Laffitte, Bryan (16 November 2017). "Discovery of Tropifexor (LJN452), a Highly Potent Non-bile Acid FXR Agonist for the Treatment of Cholestatic Liver Diseases and Nonalcoholic Steatohepatitis (NASH)". pubs.acs.org. Journal of Medicinal Chemistry. pp. 9960–9973. doi: 10.1021/acs.jmedchem.7b00907 . Retrieved . 15 May 2019
"Safety, Tolerability, and Efficacy of a Combination Treatment of Tropifexor (LJN452) and Cenicriviroc (CVC) in Adult Patients With Nonalcoholic Steatohepatitis (NASH) and Liver Fibrosis. (TANDEM)". clinicaltrials.gov. 7 May 2018 . Retrieved . 15 May 2019
WO Application Filing WO2012087519A1, Alper, Phillip B.; Chianelli, Donatella & Mutnick, Daniel et al., "Compositions and methods for modulating fxr", published 2012-06-28, assigned to Genomics Institute of the Novartis Research Foundation . Retrieved 17 May 2019.