Cilofexor

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	1418274-28-8;
PubChem CID	71228883;
IUPHAR/BPS	10644;
DrugBank	15168 DB 15168;
ChemSpider	68007315;
UNII	YUN2306954;
ChEMBL	ChEMBL4297613;
Chemical and physical data
Formula	C28H22Cl3N3O5
Molar mass	586.85 g·mol−1
3D model (JSmol)	Interactive image;
	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;

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]

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

References

^ ^a ^b Clinical trial number NCT02781584 for "Safety, Tolerability, and Efficacy of Selonsertib, Firsocostat, and Cilofexor in Adults With Nonalcoholic Steatohepatitis (NASH)" at ClinicalTrials.gov
^ ^a ^b 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
^ ^a ^b 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. PMC 7827357. PMID 33435509.
^ ^a ^b 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. PMC 6767458. PMID 30661255.
^ Clinical trial number NCT03890120 for "Safety, Tolerability, and Efficacy of Cilofexor in Non-Cirrhotic Adults With Primary Sclerosing Cholangitis (PRIMIS)" at ClinicalTrials.gov
^ ^a ^b "Gilead and Novo Nordisk Expand NASH Clinical Collaboration" (Press release). Gilead. 18 March 2021. Archived from the original on 2022-01-20.
^ 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. S2CID 211727006.
^ "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.

[NCT02781584-1] Clinical trial number NCT02781584 for "Safety, Tolerability, and Efficacy of Selonsertib, Firsocostat, and Cilofexor in Adults With Nonalcoholic Steatohepatitis (NASH)" at ClinicalTrials.gov

[NCT04971785-2] 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

[pmid33435509-3] 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. PMC 7827357. PMID 33435509.

[pmid30661255-4] 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. PMC 6767458. 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

[GilNovoPR-6] "Gilead and Novo Nordisk Expand NASH Clinical Collaboration" (Press release). Gilead. 18 March 2021. Archived from the original on 2022-01-20.

[pmid32115759-7] 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. S2CID 211727006.

[GileadPR-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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