Details of the Drug

General Information of Drug (ID: DMWU682)

• Drug Name: PX-102
• Synonyms: Px-102; PX20606 trans-isomer; UNII-378SU5NO8S; 378SU5NO8S; CHEMBL3822773; 1268244-85-4 (trans-isomer); 4-((1S,2S)-2-(2-CHLORO-4-((5-CYCLOPROPYL-3-(2,6-DICHLOROPHENYL)ISOXAZOL-4-YL)METHOXY)PHENYL)CYCLOPROPYL)BENZOIC ACID; Px-104; 2020096-17-5; 1268244-85-4; PX 20606; SCHEMBL17087854; 4-(2-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl)methoxy)phenyl)cyclopropyl)benzoic acid; BDBM50185707; ZINC115372389; DB15416; 4-(2-(2-Chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl)methoxy)phenyl)cyclopropyl)benzoic acid; AC-30349; PX-20606; PX-102(PX-20606); UNII-6TU6SUZ3BY component XBUXXJUEBFDQHD-NHCUHLMSSA-N; Benzoic acid, 4-((1R,2R)-2-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl)methoxy)phenyl)cyclopropyl)-, rel-(-)-; Benzoic acid, 4-(2-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)-4-isoxazolyl)methoxy)phenyl)cyclopropyl)-

Indication

Disease Entry	ICD 11	Status	REF
Hepatic fibrosis	DB93.0	Phase 1	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 554.8
  Topological Polar Surface Area (xlogp); 7.6
  Rotatable Bond Count (rotbonds); 8
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 5
• Chemical Identifiers:
  Formula: C29H22Cl3NO4
  IUPAC Name: 4-[(1S,2S)-2-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]cyclopropyl]benzoic acid
  Canonical SMILES: C1CC1C2=C(C(=NO2)C3=C(C=CC=C3Cl)Cl)COC4=CC(=C(C=C4)[C@H]5C[C@@H]5C6=CC=C(C=C6)C(=O)O)Cl
  InChI: InChI=1S/C29H22Cl3NO4/c30-23-2-1-3-24(31)26(23)27-22(28(37-33-27)16-6-7-16)14-36-18-10-11-19(25(32)12-18)21-13-20(21)15-4-8-17(9-5-15)29(34)35/h1-5,8-12,16,20-21H,6-7,13-14H2,(H,34,35)/t20-,21-/m1/s1
  InChIKey: XBUXXJUEBFDQHD-NHCUHLMSSA-N
• Cross-matching ID:
  PubChem CID: 118374999
  CAS Number: 1268244-85-4
  DrugBank ID: DB15416
  TTD ID: D7LQJ8

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	[2]

Molecular Expression Atlas of This Drug

• The Studied Disease: Hepatic fibrosis
• ICD Disease Classification: DB93.0

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

References

• [1] ClinicalTrials.gov (NCT01998659) Single Ascending Oral Dose Phase I Study With Px-102. U.S. National Institutes of Health.
• [2] An FXR Agonist Reduces Bile Acid Synthesis Independently of Increases in FGF19 in Healthy Volunteers. Gastroenterology. 2018 Oct;155(4):1012-1016.
• [3] 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.
• [4] 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.
• [5] 2016 FDA drug approvals. Nat Rev Drug Discov. 2017 Feb 2;16(2):73-76.
• [6] 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.
• [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.