Details of the Drug

General Information of Drug (ID: DM936V7)

Drug Name

GS-9674

Synonyms

Cilofexor; 1418274-28-8; UNII-YUN2306954; PX104; 1418274-28-8 (free acid); YUN2306954; 2-(3-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)phenyl)-3-hydroxyazetidin-1-yl)isonicotinic acid; GS 9674; 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; Cilofexor [INN]; Cilofexor (GS(c)\\9674); CHEMBL4297613; SCHEMBL14641986; GTPL10644; BCP29283; BDBM50511109; GS9674; s6547; DB15168; example 13/9 [US10485795B2]; HY-109083; CS-0039260; 2-(3-(2-Chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl)methoxy)phenyl)-3-hydroxy-1-azetidinyl)-4-pyridinecarboxylic acid; 4-Pyridinecarboxylic acid, 2-(3-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl)methoxy)phenyl)-3-hydroxy-1-azetidinyl)-

Indication

Disease Entry	ICD 11	Status	REF
Primary sclerosing cholangitis	DB96.2	Phase 3	[1]
Non-alcoholic steatohepatitis	DB92.1	Phase 2	[2]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 2

Molecular Weight (mw)

586.8

Topological Polar Surface Area (xlogp)

5.3

Rotatable Bond Count (rotbonds)

8

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

8

Chemical Identifiers

Formula: C28H22Cl3N3O5
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
Canonical 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=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)
InChIKey: KZSKGLFYQAYZCO-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 71228883
CAS Number: 1418274-28-8
TTD ID: DBND71

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Farnesoid X-activated receptor (FXR)	TTS4UGC	NR1H4_HUMAN	Agonist	[3]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Primary sclerosing cholangitis

ICD Disease Classification

DB96.2

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Farnesoid X-activated receptor (FXR)	DTT	NR1H4	5.72E-01	0.39	1.68

Molecular Expression Atlas (MEA)

MEA Detail

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References

1	ClinicalTrials.gov (NCT03890120) Safety, Tolerability, and Efficacy of Cilofexor in Non-Cirrhotic Adults With Primary Sclerosing Cholangitis (PRIMIS). U.S. National Institutes of Health.
2	ClinicalTrials.gov (NCT03449446) Study to Evaluate the Safety and Efficacy of Selonsertib, Firsocostat, Cilofexor, and Combinations in Participants With Bridging Fibrosis or Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH) (ATLAS). U.S. National Institutes of Health.
3	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.
4	Lithocholic acid decreases expression of bile salt export pump through farnesoid X receptor antagonist activity. J Biol Chem. 2002 Aug 30;277(35):31441-7.
5	Effect of guggulsterone and cembranoids of Commiphora mukul on pancreatic phospholipase A(2): role in hypocholesterolemia. J Nat Prod. 2009 Jan;72(1):24-8.
6	2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.
7	The nuclear receptors FXR and LXRalpha: potential targets for the development of drugs affecting lipid metabolism and neoplastic diseases. Curr Pharm Des. 2001 Mar;7(4):231-59.
8	FXR modulators for enterohepatic and metabolic diseases.Expert Opin Ther Pat. 2018 Nov;28(11):765-782.
9	Clinical pipeline report, company report or official report of ENYO Pharma.
10	A novel non-bile acid FXR agonist EDP-305 potently suppresses liver injury and fibrosis without worsening of ductular reaction. Liver Int. 2020 Jul;40(7):1655-1669.
11	Nidufexor (LMB763), a Novel FXR Modulator for the Treatment of Nonalcoholic Steatohepatitis. J Med Chem. 2020 Apr 23;63(8):3868-3880.
12	Clinical pipeline report, company report or official report of Metacrine.