Cilofexor

Cilofexor (also known as GS-9674) is a nonsteroidal farnesoid X receptor (FXR) agonist in clinical trials for the treatment of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH),[1][2][3] and primary sclerosing cholangitis (PSC).[4][5] It is being investigated for use alone or in combination with firsocostat, selonsertib,[1] or semaglutide.[2][6] In rat models[3] and human clinical trials[7] of NASH it has been shown to reduce fibrosis and steatosis, and in human clinical trials of PSC it improved cholestasis and reduced markers of liver injury.[4]

Cilofexor
Clinical data
ATC code
  • None
Identifiers
IUPAC name
  • 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
CAS Number
PubChem CID
UNII
Chemical and physical data
FormulaC28H22Cl3N3O5
Molar mass586.85 g·mol−1
3D model (JSmol)
SMILES
  • C1CC1C2=C(C(=NO2)C3=C(C=CC=C3Cl)Cl)COC4=CC(=C(C=C4)C5(CN(C5)C6=NC=CC(=C6)C(=O)O)O)Cl
InChI
  • InChI=InChI=1S/C28H22Cl3N3O5/c29-20-2-1-3-21(30)24(20)25-18(26(39-33-25)15-4-5-15)12-38-17-6-7-19(22(31)11-17)28(37)13-34(14-28)23-10-16(27(35)36)8-9-32-23/h1-3,6-11,15,37H,4-5,12-14H2,(H,35,36)
  • Key:KZSKGLFYQAYZCO-UHFFFAOYSA-N

It is being developed by the pharmaceutical company Gilead Sciences[8][6]

References
  1. Clinical trial number NCT02781584 for "Safety, Tolerability, and Efficacy of Selonsertib, Firsocostat, and Cilofexor in Adults With Nonalcoholic Steatohepatitis (NASH)" at ClinicalTrials.gov
  2. Clinical trial number NCT04971785 for "Study Evaluating the Safety and Efficacy of Semaglutide, and the Fixed-Dose Combination of Cilofexor and Firsocostat, Alone and in Combination, in Participants With Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)" at ClinicalTrials.gov
  3. Schwabl P, Hambruch E, Budas GR, et al. (9 Jan 2021). "The Non-Steroidal FXR Agonist Cilofexor Improves Portal Hypertension and Reduces Hepatic Fibrosis in a Rat NASH Model". Biomedicines. 9 (1): 60. doi:10.3390/biomedicines9010060. PMID 33435509.
  4. Trauner M, Gulamhusein A, Hameed B, et al. (19 January 2019). "The Nonsteroidal Farnesoid X Receptor Agonist Cilofexor (GS-9674) Improves Markers of Cholestasis and Liver Injury in Patients With Primary Sclerosing Cholangitis". Hepatology. 70 (3): 788–801. doi:10.1002/hep.30509. PMID 30661255.
  5. Clinical trial number NCT03890120 for "Safety, Tolerability, and Efficacy of Cilofexor in Non-Cirrhotic Adults With Primary Sclerosing Cholangitis (PRIMIS)" at ClinicalTrials.gov
  6. "Gilead and Novo Nordisk Expand NASH Clinical Collaboration" (Press release). Gilead. 18 March 2021. Archived from the original on 2022-01-20.
  7. Patel K, Harrison SA, Elkhashab M, et al. (9 Jan 2021). "Cilofexor, a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial". Hepatology. 72 (1): 58–71. doi:10.1002/hep.31205. PMID 32115759.
  8. "Gilead Announces Topline Results From Phase 2 ATLAS Study in Patients With Bridging Fibrosis (F3) and Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)" (Press release). Gilead. 18 March 2021. Archived from the original on 2022-01-21.
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