Tropifexor

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Tropifexor
Tropifexor.svg
Clinical data
ATC code
  • None
Identifiers
CAS Number
PubChem CID
UNII
KEGG
Chemical and physical data
FormulaC29H25F4N3O5S
Molar mass603.59 g·mol−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.[1] 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.[2]
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.[3]

References[edit]

  1. ^ 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.
  2. ^ "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.
  3. ^ 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.