Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMWU682)

• Drug Name: PX-102 Drug Info
• 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]

• Cross-matching ID:
  PubChem CID: 118374999
  ChEBI ID: CHEMBL3822773
  CAS Number: CAS 1268244-85-4
  TTD Drug ID: DMWU682

Molecule-Related Drug Atlas

Drug(s) Targeting Farnesoid X-activated receptor (FXR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Chenodiol	DMQ8JIK	Cholelithiasis	DC11	Approved	[4]
Guggulsterone	DMP7LK1	Osteoarthritis	FA00-FA05	Approved	[5]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[6]
GS-9674	DM936V7	Primary sclerosing cholangitis	DB96.2	Phase 3	[7]
Apomine	DM6B9HP	Osteopetrosis	LD24.10	Phase 2	[8]
LJN452	DM3XRUH	Primary biliary cholangitis	DB96.1	Phase 2	[9]
EYP001	DM5PBLM	Non-alcoholic steatohepatitis	DB92.1	Phase 2	[10]
EDP-305	DMGJYZ8	Non-alcoholic steatohepatitis	DB92.1	Phase 2	[11]
LMB763	DMQOXNL	Diabetic nephropathy	GB61.Z	Phase 2	[12]
MET409	DM89QXT	Non-alcoholic steatohepatitis	DB92.1	Phase 2	[13]

Drug(s) Affected By Nuclear receptor subfamily 0 group B member 2 (NR0B2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Calcipotriol	DM03CP7	Psoriasis	EA90	Approved	[14]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[15]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[16]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[17]
Clavulanate	DM2FGRT	Bacteremia	1A73	Approved	[18]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[15]
Thioridazine	DM35M8J	Schizophrenia	6A20	Approved	[19]
Deoxycholic acid	DM3GYAL	Subcutaneous fat disorder	EF02	Approved	[20]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[21]
Fluoxetine	DM3PD2C	Bipolar depression		Approved	[15]

Drug(s) Affected By Bcl2-associated agonist of cell death (BAD)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[22]
Aprepitant	DM053KT	Depression	6A70-6A7Z	Approved	[23]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[24]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[25]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[26]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[27]
obeticholic acid	DM3Q1SM	Primary biliary cholangitis	DB96.1	Approved	[28]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[29]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[30]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[31]

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]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Bcl2-associated agonist of cell death (BAD)	OT63ERYM	BAD_HUMAN	Gene/Protein Processing	[3]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Gene/Protein Processing	[3]

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] Farnesoid X receptor (FXR) agonists induce hepatocellular apoptosis and impair hepatic functions via FXR/SHP pathway. Arch Toxicol. 2022 Jun;96(6):1829-1843. doi: 10.1007/s00204-022-03266-6. Epub 2022 Mar 10.
• [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 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.
• [8] 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.
• [9] FXR modulators for enterohepatic and metabolic diseases.Expert Opin Ther Pat. 2018 Nov;28(11):765-782.
• [10] Clinical pipeline report, company report or official report of ENYO Pharma.
• [11] 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.
• [12] Nidufexor (LMB763), a Novel FXR Modulator for the Treatment of Nonalcoholic Steatohepatitis. J Med Chem. 2020 Apr 23;63(8):3868-3880.
• [13] Clinical pipeline report, company report or official report of Metacrine.
• [14] Adaptive homeostasis of the vitamin D-vitamin D nuclear receptor axis in 8-methoxypsoralen-induced hepatotoxicity. Toxicol Appl Pharmacol. 2019 Jan 1;362:150-158. doi: 10.1016/j.taap.2018.11.002. Epub 2018 Nov 10.
• [15] A toxicogenomic approach to drug-induced phospholipidosis: analysis of its induction mechanism and establishment of a novel in vitro screening system. Toxicol Sci. 2005 Feb;83(2):282-92.
• [16] Arsenite and cadmium promote the development of mammary tumors. Carcinogenesis. 2020 Jul 14;41(7):1005-1014. doi: 10.1093/carcin/bgz176.
• [17] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [18] Molecular mechanisms of hepatotoxic cholestasis by clavulanic acid: Role of NRF2 and FXR pathways. Food Chem Toxicol. 2021 Dec;158:112664. doi: 10.1016/j.fct.2021.112664. Epub 2021 Nov 9.
• [19] Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells. Toxicol Sci. 2007 Mar;96(1):101-14.
• [20] Farnesoid X receptor induces murine scavenger receptor Class B type I via intron binding. PLoS One. 2012;7(4):e35895. doi: 10.1371/journal.pone.0035895. Epub 2012 Apr 23.
• [21] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [22] Susceptibility to drug-induced apoptosis correlates with differential modulation of Bad, Bcl-2 and Bcl-xL protein levels. Cell Death Differ. 2000 Jun;7(6):574-86. doi: 10.1038/sj.cdd.4400688.
• [23] Neurokinin-1 receptor (NK1R) inhibition sensitizes APL cells to anti-tumor effect of arsenic trioxide via restriction of NF-B axis: Shedding new light on resistance to Aprepitant. Int J Biochem Cell Biol. 2018 Oct;103:105-114. doi: 10.1016/j.biocel.2018.08.010. Epub 2018 Aug 23.
• [24] Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
• [25] Sulindac sulfide inhibits epidermal growth factor-induced phosphorylation of extracellular-regulated kinase 1/2 and Bad in human colon cancer cells. Cancer Res. 2003 Feb 1;63(3):616-20.
• [26] Simvastatin induces activation of the serine-threonine protein kinase AKT and increases survival of isolated human pancreatic islets. Transplantation. 2002 Oct 27;74(8):1063-9. doi: 10.1097/00007890-200210270-00001.
• [27] Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3). Mol Cell Biochem. 2010 Nov;344(1-2):173-84. doi: 10.1007/s11010-010-0540-4. Epub 2010 Jul 25.
• [28] Pharmacotoxicology of clinically-relevant concentrations of obeticholic acid in an organotypic human hepatocyte system. Toxicol In Vitro. 2017 Mar;39:93-103.
• [29] Down regulation of N-acetylglucosaminyltransferase V facilitates all-transretinoic acid to induce apoptosis of human hepatocarcinoma cells. Mol Cell Biochem. 2006 Mar;284(1-2):103-10. doi: 10.1007/s11010-005-9022-5. Epub 2006 Jan 13.
• [30] Arsenic trioxide induces different gene expression profiles of genes related to growth and apoptosis in glioma cells dependent on the p53 status. Mol Biol Rep. 2008 Sep;35(3):421-9.
• [31] Lunasin, a novel seed peptide, sensitizes human breast cancer MDA-MB-231 cells to aspirin-arrested cell cycle and induced apoptosis. Chem Biol Interact. 2010 Jul 30;186(2):127-34. doi: 10.1016/j.cbi.2010.04.027. Epub 2010 May 21.