| Identification | Back Directory | [Name]
Cilofexor | [CAS]
1418274-28-8 | [Synonyms]
CS-2761
Cilofexor
Cilofexor （GS-9674)
GS-9674;GS9674;CILOFEXOR
2-(3-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)phenyl)-3-hydroxyazetidin-1-yl)isonicotinic acid
4-Pyridinecarboxylic acid, 2-[3-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methoxy]phenyl]-3-hydroxy-1-azetidinyl]-
2-[3-(2-chloro-4-{[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy}phenyl)-3-hydroxyazetidin-1-yl]pyridine-4-carboxylic acid | [Molecular Formula]
C28H22Cl3N3O5 | [MDL Number]
MFCD31731099 | [MOL File]
1418274-28-8.mol | [Molecular Weight]
586.85 |
| Chemical Properties | Back Directory | [Boiling point ]
855.5±65.0 °C(Predicted) | [density ]
1.538±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO:32.5(Max Conc. mg/mL);55.38(Max Conc. mM) | [form ]
A crystalline solid | [pka]
2.10±0.10(Predicted) | [color ]
Off-white to light yellow | [InChIKey]
KZSKGLFYQAYZCO-UHFFFAOYSA-N | [SMILES]
C1(N2CC(C3=CC=C(OCC4=C(C5CC5)ON=C4C4=C(Cl)C=CC=C4Cl)C=C3Cl)(O)C2)=NC=CC(C(O)=O)=C1 |
| Hazard Information | Back Directory | [Description]
Cilofexor inhibits binding of a synthetic peptide, comprising residues 676-700 of the steroid receptor coactivator 1 (SRC-1), to the farnesoid X receptor (FXR; EC50 = <25 nM in a FRET activity assay).1 It has FXR agonist activity in a mammalian one hybrid (M1H) assay (EC50 = ≥100 nM). | [Uses]
Cilofexor (GS-9674) is a potent, selective and orally active nonsteroidal FXR agonist with an EC50 of 43 nM. Cilofexor has anti-inflammatory and antifibrotic effects. Cilofexor has the potential for primary sclerosing cholangitis (PSC) and nonalcoholic steatohepatitis (NASH) research[1][2]. | [in vivo]
Cilofexor (GS-9674; 30 mg/kg; oral gavage; once daily; for 10 weeks; male Wistar rats) treatment significantly increases Fgf15 expression in the ileum and decreased Cyp7a1 in the liver in nonalcoholic steatohepatitis (NASH) rats. Liver fibrosis and hepatic collagen expression are significantly reduced. Cilofexor also significantly reduces hepatic stellate cell (HSC) activation and significantly decreases portal pressure, without affecting systemic hemodynamics[3]. | Animal Model: | Male Wistar rats received a choline-deficient high fat diet (CDHFD)[3] | | Dosage: | 30 mg/kg | | Administration: | Oral gavage; once daily; for 10 weeks | | Result: | Significantly increased Fgf15 expression in the ileum and decreased Cyp7a1 in the liver. Liver fibrosis and hepatic collagen expression were significantly reduced.
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| [storage]
Store at -20°C | [References]
[1] Trauner M, et al. The Nonsteroidal Farnesoid X Receptor Agonist Cilofexor (GS-9674) Improves Markers of Cholestasis and Liver Injury in Patients With Primary Sclerosing Cholangitis. Hepatology. 2019 Sep;70(3):788-801. DOI:10.1002/hep.30509
[2] Patel K, et al. Cilofexor, a Nonsteroidal FXR Agonist, in Non-Cirrhotic Patients with Nonalcoholic Steatohepatitis: A Phase 2 Randomized Controlled Trial. Hepatology. 2020 Mar 1. DOI:10.1002/hep.31205
[3] P. Schwab, et al. The FXR agonist GS-9674 reduces fibrosis and portal hypertension in a rat model of NASH. April 2018,Volume 68, Supplement 1, Pages S471-S472. |
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