Tropifexor

• CAT Number: I009471
• CAS Number: 1383816-29-2
• Molecular Formula: C29H25F4N3O5S
• Molecular Weight: 603.589
• Purity: ≥95%
• Target: farnesoid X receptor agonist
• Solubility: Soluble in DMSO
• Storage: 0 - 4 °C for short term, or -20 °C for long term
• IUPAC Name: 2-[(1R,5S)-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
• InChI: InChI=1S/C29H25F4N3O5S/c30-21-9-15(27(37)38)10-23-25(21)34-28(42-23)36-16-7-8-17(36)12-18(11-16)39-13-20-24(35-41-26(20)14-5-6-14)19-3-1-2-4-22(19)40-29(31,32)33/h1-4,9-10,14,16-18H,5-8,11-13H2,(H,37,38)/t16-,17+,18?
• InChIKey: VYLOOGHLKSNNEK-JWTNVVGKSA-N
• SMILES: C1CC1C2=C(C(=NO2)C3=CC=CC=C3OC(F)(F)F)COC4CC5CCC(C4)N5C6=NC7=C(C=C(C=C7S6)C(=O)O)F

Tropifexor(cas# 1383816-29-2), also known as LJN452, is a farnesoid X receptor agonist for the Treatment of Cholestatic Liver Diseases and Nonalcoholic Steatohepatitis (NASH). Potent in vivo activity was demonstrated in rodent PD models by measuring the induction of FXR target genes in various tissues. Tropifexor has advanced into phase 2 human clinical trials in patients with NASH and PBC.

Reference

1. J Med Chem. 2017 Dec 8. doi: 10.1021/acs.jmedchem.7b00907. [Epub ahead of print]

Discovery of Tropifexor (LJN452), a Highly Potent Non-bile Acid FXR Agonist for
the Treatment of Cholestatic Liver Diseases and Nonalcoholic Steatohepatitis
(NASH).

Tully DC(1)(2), Rucker PV(1), Chianelli D(1), Williams J(1), Vidal A(1), Alper
PB(1), Mutnick D(1), Bursulaya B(1), Schmeits J(1), Wu X(1), Bao D(1), Zoll J(1),
Kim Y(1), Groessl T(1), McNamara P(1), Seidel HM(1), Molteni V(1), Liu B(1),
Phimister A(2), Joseph SB(1), Laffitte B(1).

Author information:
(1)Genomics Institute of the Novartis Research Foundation , San Diego, California
92121, United States.
(2)Novartis Institutes for Biomedical Research , Emeryville, California 94608,
United States.

The farnesoid X receptor (FXR) is a nuclear receptor that acts as a master
regulator of bile acid metabolism and signaling. Activation of FXR inhibits bile
acid synthesis and increases bile acid conjugation, transport, and excretion,
thereby protecting the liver from the harmful effects of bile accumulation,
leading to considerable interest in FXR as a therapeutic target for the treatment
of cholestasis and nonalcoholic steatohepatitis. We identified a novel series of
highly potent non-bile acid FXR agonists that introduce a bicyclic
nortropine-substituted benzothiazole carboxylic acid moiety onto a trisubstituted
isoxazole scaffold. Herein, we report the discovery of 1 (tropifexor, LJN452), a
novel and highly potent agonist of FXR. Potent in vivo activity was demonstrated
in rodent PD models by measuring the induction of FXR target genes in various
tissues. Tropifexor has advanced into phase 2 human clinical trials in patients
with NASH and PBC.