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MedKoo Cat#: 561844 | Name: Cilofexor
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Cilofexor, also known as GS-9674, is a farnesoid X receptor (FXR) agonist. The nonsteroidal FXR agonist cilofexor (GS-9674) improves markers of cholestasis and liver injury in patients with PSC. In clinical study, cilofexor was well tolerated and led to significant improvements in liver biochemistries and markers of cholestasis in patients with PSC.

Chemical Structure

Cilofexor
Cilofexor
CAS#1418274-28-8 (free acid)

Theoretical Analysis

MedKoo Cat#: 561844

Name: Cilofexor

CAS#: 1418274-28-8 (free acid)

Chemical Formula: C28H22Cl3N3O5

Exact Mass: 585.0625

Molecular Weight: 586.85

Elemental Analysis: C, 57.31; H, 3.78; Cl, 18.12; N, 7.16; O, 13.63

Price and Availability

Size Price Availability Quantity
10mg USD 190.00 Ready to ship
25mg USD 350.00 Ready to ship
50mg USD 550.00 Ready to ship
100mg USD 950.00 Ready to ship
200mg USD 1,650.00 Ready to ship
500mg USD 2,950.00 2 Weeks
1g USD 4,250.00 2 Weeks
2g USD 6,950.00 2 Weeks
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Related CAS #
2253764-93-9 (tromethamine) 1418274-28-8 (free acid)
Synonym
Cilofexor; GS-9674; GS 9674; GS9674;
IUPAC/Chemical Name
2-(3-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)phenyl)-3-hydroxyazetidin-1-yl)isonicotinic acid
InChi Key
KZSKGLFYQAYZCO-UHFFFAOYSA-N
InChi Code
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)
SMILES Code
OC(C1=CC=NC(N2CC(O)(C2)C3=C(C=C(C=C3)OCC4=C(ON=C4C5=C(C=CC=C5Cl)Cl)C6CC6)Cl)=C1)=O
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, DMF, EtOH (slightly), and 1:20 DMF:PBS
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Biological target:
Cilofexor (GS-9674) is a potent and selectivenonsteroidal FXR agonist with an EC50 of 43 nM.
In vitro activity:
TBD
In vivo activity:
This experiment studied the effects of the non-steroidal FXR agonist cilofexor (formerly GS-9674) on portal pressure and fibrosis in experimental NASH. NASH was induced in Wistar rats using a choline-deficient high-fat diet plus intraperitoneal sodium nitrite injections. First, a dose-finding study was performed with 10 mg/kg and 30 mg/kg of cilofexor, focusing on histological readouts. In a subsequent hemodynamic study, rats received 30 mg/kg cilofexor with or without propranolol (25 mg/kg). Portal pressure, systemic hemodynamics and splanchnic blood flow were measured. Cilofexor dose-dependently induced FXR target genes shp, cyp7a1 and fgf15 in hepatic and ileal tissues, paralleled by a dose-dependent reduction in liver fibrosis area (Picro-Sirius-Red) of -41% (10 mg/kg) and -69% (30 mg/kg), respectively. The 30 mg/kg cilofexor dose significantly reduced hepatic hydroxyproline content (-41%), expression of col1a1 (-37%) and pdgfr-β (-36%), as well as desmin area (-42%) in NASH rats. Importantly, cilofexor decreased portal pressure (11.9 ± 2.1 vs. 8.9 ± 2.2 mmHg; p = 0.020) without affecting splanchnic blood-flow or systemic hemodynamics. The addition of propranolol to cilofexor additionally reduced splanchnic inflow (-28%) but also mean arterial pressure (-25%) and heart rate (37%). In conclusion, the non-steroidal FXR agonist cilofexor decreased portal hypertension and reduced liver fibrosis in NASH rats. Reference: Biomedicines. 2021 Jan 9;9(1):60. https://pubmed.ncbi.nlm.nih.gov/33435509/
Solvent mg/mL mM
Solubility
DMSO 32.5 55.38
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 586.85 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Schwabl P, Hambruch E, Budas GR, Supper P, Burnet M, Liles JT, Birkel M, Brusilovskaya K, Königshofer P, Peck-Radosavljevic M, Watkins WJ, Trauner M, Breckenridge DG, Kremoser C, Reiberger T. The Non-Steroidal FXR Agonist Cilofexor Improves Portal Hypertension and Reduces Hepatic Fibrosis in a Rat NASH Model. Biomedicines. 2021 Jan 9;9(1):60. doi: 10.3390/biomedicines9010060. PMID: 33435509; PMCID: PMC7827357
In vitro protocol:
TBD
In vivo protocol:
1. Schwabl P, Hambruch E, Budas GR, Supper P, Burnet M, Liles JT, Birkel M, Brusilovskaya K, Königshofer P, Peck-Radosavljevic M, Watkins WJ, Trauner M, Breckenridge DG, Kremoser C, Reiberger T. The Non-Steroidal FXR Agonist Cilofexor Improves Portal Hypertension and Reduces Hepatic Fibrosis in a Rat NASH Model. Biomedicines. 2021 Jan 9;9(1):60. doi: 10.3390/biomedicines9010060. PMID: 33435509; PMCID: PMC7827357
1: Alkhouri N, Herring R, Kabler H, Kayali Z, Hassanein T, Kohli A, Huss RS, Zhu Y, Billin AN, Damgaard LH, Buchholtz K, Kjær MS, Balendran C, Myers RP, Loomba R, Noureddin M. Safety and efficacy of combination therapy with semaglutide, cilofexor and firsocostat in patients with non-alcoholic steatohepatitis: A randomised, open-label phase II trial. J Hepatol. 2022 Sep;77(3):607-618. doi: 10.1016/j.jhep.2022.04.003. Epub 2022 Apr 16. PMID: 35439567. 2: Loomba R, Noureddin M, Kowdley KV, Kohli A, Sheikh A, Neff G, Bhandari BR, Gunn N, Caldwell SH, Goodman Z, Wapinski I, Resnick M, Beck AH, Ding D, Jia C, Chuang JC, Huss RS, Chung C, Subramanian GM, Myers RP, Patel K, Borg BB, Ghalib R, Kabler H, Poulos J, Younes Z, Elkhashab M, Hassanein T, Iyer R, Ruane P, Shiffman ML, Strasser S, Wong VW, Alkhouri N; for the ATLAS Investigators. Combination Therapies Including Cilofexor and Firsocostat for Bridging Fibrosis and Cirrhosis Attributable to NASH. Hepatology. 2021 Feb;73(2):625-643. doi: 10.1002/hep.31622. PMID: 33169409. 3: Polyzos SA, Xanthopoulos K, Kountouras J. Cilofexor for the Treatment of Nonalcoholic Steatohepatitis. Curr Vasc Pharmacol. 2022;20(2):111-113. doi: 10.2174/1570161119666211209161023. PMID: 34886776. 4: Patel K, Harrison SA, Elkhashab M, Trotter JF, Herring R, Rojter SE, Kayali Z, Wong VW, Greenbloom S, Jayakumar S, Shiffman ML, Freilich B, Lawitz EJ, Gane EJ, Harting E, Xu J, Billin AN, Chung C, Djedjos CS, Subramanian GM, Myers RP, Middleton MS, Rinella M, Noureddin M. Cilofexor, a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial. Hepatology. 2020 Jul;72(1):58-71. doi: 10.1002/hep.31205. PMID: 32115759. 5: Jiang L, Liu X, Wei H, Dai S, Qu L, Chen X, Guo M, Chen Y. Structural insight into the molecular mechanism of cilofexor binding to the farnesoid X receptor. Biochem Biophys Res Commun. 2022 Mar 5;595:1-6. doi: 10.1016/j.bbrc.2022.01.069. Epub 2022 Jan 21. Erratum in: Biochem Biophys Res Commun. 2022 Feb 22;: PMID: 35091108. 6: Polyzos SA, Katsiki N. Semaglutide, cilofexor, and firsocostat for nonalcoholic steatohepatitis: a dance that may need more than one dancer. Hormones (Athens). 2022 Sep;21(3):513-514. doi: 10.1007/s42000-022-00379-6. Epub 2022 Jun 6. PMID: 35668318. 7: Björnsson ES, Kalaitzakis E. Recent advances in the treatment of primary sclerosing cholangitis. Expert Rev Gastroenterol Hepatol. 2021 Apr;15(4):413-425. doi: 10.1080/17474124.2021.1860751. Epub 2020 Dec 14. PMID: 33283566. 8: Fiorucci S, Biagioli M, Sepe V, Zampella A, Distrutti E. Bile acid modulators for the treatment of nonalcoholic steatohepatitis (NASH). Expert Opin Investig Drugs. 2020 Jun;29(6):623-632. doi: 10.1080/13543784.2020.1763302. Epub 2020 Jun 19. PMID: 32552182. 9: Schwabl P, Hambruch E, Budas GR, Supper P, Burnet M, Liles JT, Birkel M, Brusilovskaya K, Königshofer P, Peck-Radosavljevic M, Watkins WJ, Trauner M, Breckenridge DG, Kremoser C, Reiberger T. The Non-Steroidal FXR Agonist Cilofexor Improves Portal Hypertension and Reduces Hepatic Fibrosis in a Rat NASH Model. Biomedicines. 2021 Jan 9;9(1):60. doi: 10.3390/biomedicines9010060. PMID: 33435509; PMCID: PMC7827357. 10: Xu J, Wang Y, Khoshdeli M, Peach M, Chuang JC, Lin J, Tsai WW, Mahadevan S, Minto W, Diehl L, Gupta R, Trauner M, Patel K, Noureddin M, Kowdley KV, Gulamhusein A, Bowlus CL, Huss RS, Myers RP, Chung C, Billin AN. IL-31 levels correlate with pruritus in patients with cholestatic and metabolic liver diseases and is farnesoid X receptor responsive in NASH. Hepatology. 2023 Jan 1;77(1):20-32. doi: 10.1002/hep.32599. Epub 2022 Jul 17. PMID: 35686937; PMCID: PMC9970017. 11: Kovalic AJ, Gozar M, Da BL, Bernstein D, Satapathy SK. Pharmacotherapeutic efficacy on noninvasive fibrosis progression in nonalcoholic fatty liver disease: a systematic review and network meta-analysis. Eur J Gastroenterol Hepatol. 2023 Jan 1;35(1):102-111. doi: 10.1097/MEG.0000000000002463. Epub 2022 Nov 17. PMID: 36468574. 12: Lawitz EJ, Bhandari BR, Ruane PJ, Kohli A, Harting E, Ding D, Chuang JC, Huss RS, Chung C, Myers RP, Loomba R. Fenofibrate Mitigates Hypertriglyceridemia in Nonalcoholic Steatohepatitis Patients Treated With Cilofexor/Firsocostat. Clin Gastroenterol Hepatol. 2023 Jan;21(1):143-152.e3. doi: 10.1016/j.cgh.2021.12.044. Epub 2022 Jan 6. PMID: 34999207. 13: Jindal A, Sarin SK. Letter to the Editor: Cilofexor in Patients With Nonalcoholic Steatohepatitis (NASH): Is It Really Effective? Hepatology. 2020 Dec;72(6):2240-2241. doi: 10.1002/hep.31400. Epub 2020 Nov 16. PMID: 32488894. 14: Trauner M, Gulamhusein A, Hameed B, Caldwell S, Shiffman ML, Landis C, Eksteen B, Agarwal K, Muir A, Rushbrook S, Lu X, Xu J, Chuang JC, Billin AN, Li G, Chung C, Subramanian GM, Myers RP, Bowlus CL, Kowdley KV. 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. Epub 2019 Mar 10. PMID: 30661255; PMCID: PMC6767458. 15: Younis IR, Kirby BJ, Billin AN, Xiao D, Song Q, Watkins TR, Othman AA. Pharmacokinetics, pharmacodynamics, safety and tolerability of cilofexor, a novel nonsteroidal Farnesoid X receptor agonist, in healthy volunteers. Clin Transl Sci. 2023 Mar;16(3):536-547. doi: 10.1111/cts.13469. Epub 2023 Jan 15. PMID: 36573450; PMCID: PMC10014688. 16: Weber E, Younis IR, Nelson C, Ding D, Qin A, Xiao D, Watkins TR, Othman AA. Effect of Renal Impairment on the Pharmacokinetics of Firsocostat, an Acetyl- Coenzyme A Carboxylase Inhibitor, and Cilofexor, a Selective Nonsteroidal Farnesoid X Receptor Agonist. J Clin Pharmacol. 2023 May;63(5):560-568. doi: 10.1002/jcph.2206. Epub 2023 Feb 28. PMID: 36700458. 17: Younis I, Weber E, Nelson C, Kirby BJ, Shen G, Xiao D, Watkins TR, Othman AA. Evaluation of the Potential for Cytochrome P450 and Transporter-Mediated Drug-Drug Interactions for Cilofexor, a Selective Nonsteroidal Farnesoid X Receptor (FXR) Agonist. Clin Pharmacokinet. 2023 Apr;62(4):609-621. doi: 10.1007/s40262-023-01214-w. Epub 2023 Mar 11. PMID: 36906733; PMCID: PMC10085937. 18: Jiang L, Liu X, Wei H, Dai S, Qu L, Chen X, Guo M, Chen Y. Corrigendum to "Structural insight into the molecular mechanism of cilofexor binding to the farnesoid X receptor" [Biochem. Biophys. Res. Commun. 595(5) 2022 1-6]. Biochem Biophys Res Commun. 2022 Apr 16;600:163-164. doi: 10.1016/j.bbrc.2022.02.036. Epub 2022 Feb 23. Erratum for: Biochem Biophys Res Commun. 2022 Mar 5;595:1-6. PMID: 35216802. 19: Younis IR, Hsueh CH, Nelson C, Billin AN, Yue MS, Xiao D, Watkins TR, Othman AA. Effect of Hepatic Impairment on the Pharmacokinetics and Pharmacodynamics of Cilofexor, a Selective Nonsteroidal Farnesoid X Receptor Agonist. J Clin Pharmacol. 2023 May 1. doi: 10.1002/jcph.2260. Epub ahead of print. PMID: 37128693. 20: Trauner M, Bowlus CL, Gulamhusein A, Hameed B, Caldwell SH, Shiffman ML, Landis C, Muir AJ, Billin A, Xu J, Liu X, Lu X, Chung C, Myers RP, Kowdley KV. Safety and Sustained Efficacy of the Farnesoid X Receptor (FXR) Agonist Cilofexor Over a 96-Week Open-label Extension in Patients With PSC. Clin Gastroenterol Hepatol. 2023 Jun;21(6):1552-1560.e2. doi: 10.1016/j.cgh.2022.07.024. Epub 2022 Aug 4. PMID: 35934287.

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NEU-4438

NEU-4438