/Combination Treatments For Cholestasis
Abstract

A method of treating a cholestasis liver condition in a subject in need of such therapy, comprising: coadministering to the subject a first compound and a second compound, wherein the first compound is selected from the group consisting of (1) a muricholic acid (MCA) or a pharmaceutically acceptable salt thereof, and (2) an apical sodium-dependent bile acid transporter (ASBT) inhibitor, and the second compound is selected from the group consisting of (1) a CYP7A1 inhibitor and (2) a bile acid-activated farnesoid x receptor (FXR) agonist. Examples of MCAs include α-MCA, β-MCA, ω-MCA, glycine-conjugated α-MCA (G-α-MCA), glycine-conjugated β-MCA (G-β-MCA), glycine-conjugated ω-MCA (G-ω-MCA), taurine-conjugated α-MCA (T-α-MCA), taurine-conjugated β-MCA (T-β-MCA), and taurine-conjugated ω-MCA (T-ω-MCA) and a pharmaceutically-acceptable salts of any of the above. The CYP7A1 inhibitor may be a fibroblast growth factor 15 (FGF15) or FGF15 analogue, a fibroblast growth factor 19 (FGF19) or FGF19 analogue, or an anti-CYP7A1 siRNA.

Full Text

What is claimed is:

A method of treating a cholestasis liver condition in a subject in need of such therapy, comprising: coadministering to the subject a first compound and a second compound, wherein the first compound is selected from the group consisting of (1) a muricholic acid (MCA) or a pharmaceutically acceptable salt thereof, and (2) an apical sodium-dependent bile acid transporter (ASBT) inhibitor, and the second compound is selected from the group consisting of (1) a CYP7A1 inhibitor and (2) a bile acid-activated farnesoid x receptor (FXR) agonist. Examples of MCAs include α-MCA, β-MCA, ω-MCA, glycine-conjugated α-MCA (G-α-MCA), glycine-conjugated β-MCA (G-β-MCA), glycine-conjugated ω-MCA (G-ω-MCA), taurine-conjugated α-MCA (T-α-MCA), taurine-conjugated β-MCA (T-β-MCA), and taurine-conjugated ω-MCA (T-ω-MCA) and a pharmaceutically-acceptable salts of any of the above. The CYP7A1 inhibitor may be a fibroblast growth factor 15 (FGF15) or FGF15 analogue, a fibroblast growth factor 19 (FGF19) or FGF19 analogue, or an anti-CYP7A1 siRNA.
Timeline
Filed
05/21/2026
Published
09/17/2026
Granted
Not Available
IPC Codes(6)
A61K 31/575:substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
A61K 31/554:having at least one nitrogen and at least one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
A61K 31/7105:Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links