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

General Information of Drug (ID: DMU2A6D)

• Drug Name: PF-4217903 Drug Info
• Synonyms: 2-(4-(1-(Quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-1H-pyrazol-1-yl)ethanol; PF-04217903; 956905-27-4; PF04217903; PF 04217903; UNII-CYJ9ATV1IJ; CYJ9ATV1IJ; 2-(4-(1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl)-1H-pyrazol-1-yl)ethanol; CHEMBL2001019; 1159490-85-3; aka PF-04217903; C19H16N8O; 2-[4-(3-Quinolin-6-ylmethyl-3H-[1,2,3]triazolo[4,5-b]pyrazin-5-yl)-pyrazol-1-yl]-ethanol; 2-(4-(1-(Quinolin-6-ylmethyl)-1H-(1,2,3)triazolo(4,5-b)pyrazin-6-yl)-1H-pyrazol-1-yl)ethanol; 3zxz; PDMUGYOXRHVNMO-UHFFFAOYSA-N; PF-04217903

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 17754438
  ChEBI ID: CHEBI:91425
  CAS Number: CAS 956905-27-4
  TTD Drug ID: DMU2A6D

Molecule-Related Drug Atlas

Drug(s) Targeting Proto-oncogene c-Met (MET)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[4]
Cabozantinib	DMIYDT4	Medullary thyroid gland carcinoma		Approved	[5]
Amivantamab	DMZ7AMY	Non-small-cell lung cancer	2C25	Approved	[6]
Capmatinib	DMYCXKL	Non-small-cell lung cancer	2C25.Y	Approved	[7]
Tepotinib	DMUQ0E8	Non-small-cell lung cancer	2C25	Approved	[8]
RG3638	DMTQJE0	Gastric adenocarcinoma	2B72	Phase 3	[9]
Savolitinib	DMALFKX	Renal cell carcinoma	2C90	Phase 3	[10]
Beperminogene perplasmid	DM6RWBN	Critical limb ischemia	BD4Y	Phase 3	[11]
Tivantinib	DMNVP8Q	Hepatocellular carcinoma	2C12.02	Phase 3	[12]
MGCD516	DM752PU	Solid tumour/cancer	2A00-2F9Z	Phase 2/3	[9]

Drug(s) Affected By Aldehyde oxidase (AOX1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[13]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[14]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[15]
Methylprednisolone	DM4BDON	Acute adrenal insufficiency		Approved	[16]
Nefazodone	DM4ZS8M	Major depressive disorder	6A70.3	Approved	[17]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[18]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[19]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[20]
Dasatinib	DMJV2EK	Blast phase chronic myelogenous leukemia, BCR-ABL1 positive		Approved	[21]
Temozolomide	DMKECZD	Adenocarcinoma	2D40	Approved	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Proto-oncogene c-Met (MET)	TTNDSF4	MET_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Aldehyde oxidase (AOX1)	OT2FZP6H	AOXA_HUMAN	Regulation of Drug Effects	[3]

References

• [1] ClinicalTrials.gov (NCT00706355) A Study of PF-04217903 in Patients With Advanced Cancer. U.S. National Institutes of Health.
• [2] Sensitivity of selected human tumor models to PF-04217903, a novel selective c-Met kinase inhibitor. Mol Cancer Ther. 2012 Apr;11(4):1036-47.
• [3] In vitro-in vivo correlation for intrinsic clearance for drugs metabolized by human aldehyde oxidase. Drug Metab Dispos. 2010 Aug;38(8):1322-7. doi: 10.1124/dmd.110.033555. Epub 2010 May 5.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Clinical pipeline report, company report or official report of Exelixis (2011).
• [6] Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC. Cancer Discov. 2020 Aug;10(8):1194-1209.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [9] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1815).
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] Beperminogene perplasmid for the treatment of critical limb ischemia. Expert Rev Cardiovasc Ther. 2014 Oct;12(10):1145-56.
• [12] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7948).
• [13] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [14] 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.
• [15] Rofecoxib modulates multiple gene expression pathways in a clinical model of acute inflammatory pain. Pain. 2007 Mar;128(1-2):136-47.
• [16] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [17] Robustness testing and optimization of an adverse outcome pathway on cholestatic liver injury. Arch Toxicol. 2020 Apr;94(4):1151-1172. doi: 10.1007/s00204-020-02691-9. Epub 2020 Mar 10.
• [18] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [19] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [20] 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.
• [21] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [22] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.