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

General Information of Drug (ID: DM42OYU)

• Drug Name: PMID28870136-Compound-50 Drug Info
• Cross-matching ID:
  PubChem CID: 5429
  ChEBI ID: CHEBI:28946
  CAS Number: CAS 83-67-0
  TTD Drug ID: DM42OYU

Molecule-Related Drug Atlas

Drug(s) Targeting Ecto-5'-nucleotidase (CD73)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TJ004309	DMFB54Y	Ovarian cancer	2C73	Phase 2	[3]
GS-1423	DMS25DL	Solid tumour/cancer	2A00-2F9Z	Phase 1	[4]
Oleclumab	DMLVNWO	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]
AB680	DMGONUE	Pancreatic cancer	2C10	Phase 1	[6]
TJ4309	DMM3U2Q	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
CPI-006	DMJSFTX	Advanced cancer	2A00-2F9Z	Phase 1	[8]
LY3475070	DMZLIWX	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
NZV930	DMWN2FP	Solid tumour/cancer	2A00-2F9Z	Phase 1	[10]
PMID28870136-Compound-57	DME3HLC	N. A.	N. A.	Patented	[1]
PMID28870136-Compound-46	DM4FD7C	N. A.	N. A.	Patented	[1]

Drug(s) Affected By Cytochrome P450 2E1 (CYP2E1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Fomepizole	DM6VOWQ	Athylene glycol or methanol poisoning	NE61	Approved	[11]
Ademetionine	DMYQDBO	Hepatic fibrosis	DB93.0	Approved	[12]
Theophylline	DMRJFN9	Bronchitis	CA20	Approved	[13]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[14]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[15]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[16]
Phenobarbital	DMXZOCG	Cluster headache	8A81.0	Approved	[17]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[18]
Didanosine	DMI2QPE	Human immunodeficiency virus infection	1C62	Approved	[13]
Thioridazine	DM35M8J	Schizophrenia	6A20	Approved	[19]

Drug(s) Affected By Cytochrome P450 1A2 (CYP1A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Zolmitriptan	DM1IB4Q	Migraine	8A80	Approved	[20]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[20]
Etoricoxib	DM6A4NW	Rheumatoid arthritis	FA20	Approved	[20]
Capsaicin	DMGMF6V	Back pain	ME84.Z	Approved	[21]
Hesperetin	DMKER83	High blood cholesterol level	5C80.00	Approved	[22]
Stiripentol	DMMSDOY	Dravet syndrome	8A61.11	Approved	[23]
Nifedipine	DMSVOZT	Angina pectoris	BA40	Approved	[24]
Zileuton	DMVRIC2	Allergic asthma	CA23.0	Approved	[25]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[26]
Clonidine	DM6RZ9Q	Attention deficit hyperactivity disorder	6A05.Z	Approved	[13]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Ecto-5'-nucleotidase (CD73)	TTK0O6Y	5NTD_HUMAN	Inhibitor	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Biotransformations	[2]
Cytochrome P450 2E1 (CYP2E1)	OTHQ17JG	CP2E1_HUMAN	Biotransformations	[2]

References

• [1] Ectonucleotidase inhibitors: a patent review (2011-2016).Expert Opin Ther Pat. 2017 Dec;27(12):1291-1304.
• [2] Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1. Pharmacogenetics. 1992 Apr;2(2):73-7.
• [3] ClinicalTrials.gov (NCT05001347) A Phase 2 Clinical Study of TJ004309 in Combination With Atezolizumab (TECENTRIQ?) in Patients With Advanced or Metastatic Ovarian Cancers and Selected Advanced Solid Tumors. U.S.National Institutes of Health.
• [4] Clinical pipeline report, company report or official report of Agenus.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Discovery of AB680: A Potent and Selective Inhibitor of CD73. J Med Chem. 2020 Oct 22;63(20):11448-11468.
• [7] ClinicalTrials.gov (NCT04322006) A Phase I/II Study of TJ004309 for Advanced Solid Tumor. U.S. National Institutes of Health.
• [8] Clinical pipeline report, company report or official report of Corvus Pharmaceuticals.
• [9] CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers. Front Immunol. 2020 Apr 15;11:508.
• [10] Clinical pipeline report, company report or official report of Surface oncology.
• [11] Chemical inhibitors of cytochrome P450 isoforms in human liver microsomes: a re-evaluation of P450 isoform selectivity. Eur J Drug Metab Pharmacokinet. 2011 Mar;36(1):1-16.
• [12] Inhibition of CYP2E1 catalytic activity in vitro by S-adenosyl-L-methionine. Biochem Pharmacol. 2005 Apr 1;69(7):1081-93.
• [13] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [14] Characterization of primary human hepatocytes, HepG2 cells, and HepaRG cells at the mRNA level and CYP activity in response to inducers and their predictivity for the detection of human hepatotoxins. Cell Biol Toxicol. 2012 Apr;28(2):69-87.
• [15] An in vitro model of human acute ethanol exposure that incorporates CXCR3- and CXCR4-dependent recruitment of immune cells. Toxicol Sci. 2013 Mar;132(1):131-41.
• [16] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [17] Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver. Arch Toxicol. 2022 Oct;96(10):2739-2754. doi: 10.1007/s00204-022-03338-7. Epub 2022 Jul 26.
• [18] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [19] Inhibition of cytochrome P450 enzymes participating in p-nitrophenol hydroxylation by drugs known as CYP2E1 inhibitors. Chem Biol Interact. 2004 Apr 15;147(3):331-40.
• [20] In vitro inhibition of CYP1A2 by model inhibitors, anti-inflammatory analgesics and female sex steroids: predictability of in vivo interactions. Basic Clin Pharmacol Toxicol. 2008 Aug;103(2):157-65.
• [21] Effects of capsaicin and dihydrocapsaicin on human and rat liver microsomal CYP450 enzyme activities in vitro and in vivo. J Asian Nat Prod Res. 2012;14(4):382-95.
• [22] Drug interaction study of flavonoids toward CYP3A4 and their quantitative structure activity relationship (QSAR) analysis for predicting potential effects. Toxicol Lett. 2018 Sep 15;294:27-36.
• [23] Stiripentol. Expert Opin Investig Drugs. 2005 Jul;14(7):905-11.
• [24] Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52.
• [25] Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor. Drug Metab Dispos. 2003 Nov;31(11):1352-60.
• [26] Predictive three-dimensional quantitative structure-activity relationship of cytochrome P450 1A2 inhibitors. J Med Chem. 2005 Jun 2;48(11):3808-15.