February 06, 2018
Liver diseases, I’m coming after you.
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Image of Tropifexor 3D Image of Tropifexor

Nonalcoholic steatohepatitis (NASH) is a liver disease that is becoming more prevalent as worldwide obesity and type 2 diabetes increase. It is characterized by accumulation of fat in the liver, inflammation, hepatocyte ballooning, and fibrosis.

Another liver disease, primary biliary cholangitis (PBC), is a cholestatic condition in which bile flow from the liver to the intestine is reduced or interrupted. It is thought to be autoimmune.

PBC is associated with decreased expression of the farnesoid X receptor (FXR), a ligand-activated nuclear receptor that is highly expressed in the liver and other organs. FXR is a key regulator of bile acid production, conjugation, and transport. FXR activation also suppresses lipogenesis; thus, it has been proposed as a treatment for NASH.

Recently, David C. Tully and colleagues at the Genomics Institute of the Novartis Research Foundation (San Diego) and the Novartis Institutes for Biomedical Research (Emeryville, CA) discovered tropifexor, a highly potent FXR agonist. They began by replacing an indole group in an existing partial FXR agonist with a 2-substituted benzothiazole-6-carboxylic acid, a change that resulted in a dramatic increase in potency. Further changes, including optimization of the benzothiazole substituent, resulted in more potent, orally bioavailable tropifexor.

Tropifexor is safe and well tolerated at pharmacologically effective doses. It is currently in phase 2 human clinical trials on patients with PBC and NASH.

Tropifexor fast facts

CAS Reg. No.1383816-29-2
Molar mass603.58 g/mol 
Empirical formulaC29H25F4N3O5S
AppearanceWhite crystals 
Melting point221 ºC 
Water solubility6 mg/L

Tropifexor hazard information

GHS* classification: not a hazardous substance**

*Globally Harmonized System of Classification and Labeling of Chemicals.

**Current classification. This is a new substance, however, and its hazards may not have been determined.

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