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

General Information of Drug (ID: DMIYDT4)

Drug Name
Cabozantinib Drug Info
Synonyms Cabometyx; Cometriq
Indication
Disease Entry ICD 11 Status REF
Medullary thyroid gland carcinoma Approved [1]
Thyroid cancer 2D10 Approved [2]
Ovarian cancer 2C73 Phase 2 [2]
Cross-matching ID
PubChem CID
25102847
ChEBI ID
CHEBI:72317
CAS Number
CAS 849217-68-1
TTD Drug ID
DMIYDT4
INTEDE Drug ID
DR0254
ACDINA Drug ID
D00087

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DME
DOT
Drug Status:
Approved Drug(s)
Clinical Trial Drug(s)
Download the Complete Related Drug List
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 [8]
Amivantamab DMZ7AMY Non-small-cell lung cancer 2C25 Approved [9]
Capmatinib DMYCXKL Non-small-cell lung cancer 2C25.Y Approved [10]
Tepotinib DMUQ0E8 Non-small-cell lung cancer 2C25 Approved [11]
RG3638 DMTQJE0 Gastric adenocarcinoma 2B72 Phase 3 [12]
Savolitinib DMALFKX Renal cell carcinoma 2C90 Phase 3 [13]
Beperminogene perplasmid DM6RWBN Critical limb ischemia BD4Y Phase 3 [14]
Tivantinib DMNVP8Q Hepatocellular carcinoma 2C12.02 Phase 3 [15]
MGCD516 DM752PU Solid tumour/cancer 2A00-2F9Z Phase 2/3 [12]
CMX-2043 DMPSCVY Cardiac disease BA00-BE2Z Phase 2 [16]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Targeting Vascular endothelial growth factor receptor 2 (KDR)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Sorafenib DMS8IFC Adenocarcinoma 2D40 Approved [17]
Romiplostim DM3U7SZ Thrombocytopenia 3B64 Approved [18]
Regorafenib DMHSY1I Gastrointestinal stromal tumour 2B5B Approved [8]
Sunitinib DMCBJSR Acute undifferentiated leukemia Approved [19]
Axitinib DMGVH6N Renal cell carcinoma 2C90 Approved [20]
Vandetanib DMRICNP Solid tumour/cancer 2A00-2F9Z Approved [21]
Pazopanib HCl DM6U9CQ Renal cell carcinoma 2C90 Approved [22]
Fruquintinib DMHOSCQ Colorectal cancer 2B91.Z Approved [23]
Tivozanib DMUKC5L Renal cell carcinoma 2C90 Approved [24]
Lenvatinib DMB1IU4 Thyroid cancer 2D10 Approved [25]
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Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [26]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [27]
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [28]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [29]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [30]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [31]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [32]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [33]
Prasterone DM67VKL Chronic obstructive pulmonary disease CA22 Approved [27]
Verapamil DMA7PEW Angina pectoris BA40 Approved [34]
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Drug(s) Metabolized By Cytochrome P450 2C9 (CYP2C9)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Progesterone DMUY35B Amenorrhea GA20.0 Approved [35]
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [36]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [37]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [38]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [39]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [38]
Verapamil DMA7PEW Angina pectoris BA40 Approved [40]
Diclofenac DMPIHLS Chronic renal failure GB61.Z Approved [41]
Estrone DM5T6US Acne vulgaris ED80 Approved [42]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [43]
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Drug(s) Affected By Hepatocyte growth factor receptor (MET)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Crizotinib DM4F29C Non-small-cell lung cancer 2C25.Y Approved [44]
Fexofenadine DM17ONX Allergic rhinitis CA08.0 Approved [45]
Lumiracoxib DM1S4AG Chronic renal failure GB61.Z Approved [45]
Clavulanate DM2FGRT Bacteremia 1A73 Approved [45]
Methotrexate DM2TEOL Anterior urethra cancer Approved [46]
Quercetin DM3NC4M Obesity 5B81 Approved [47]
Troglitazone DM3VFPD Diabetic complication 5A2Y Approved [45]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [48]
Methylprednisolone DM4BDON Acute adrenal insufficiency Approved [46]
Penbutolol DM4ES8F Hypertension BA00-BA04 Approved [45]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Alanine aminotransferase 1 (GPT)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Halothane DM80OZ5 Anaesthesia 9A78.6 Approved [49]
Isoniazid DM5JVS3 Latent tuberculosis infection Approved [50]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [51]
Primidone DM0WX6I Epilepsy 8A60-8A68 Approved [49]
Ciprofloxacin XR DM2NLS9 Acute gonococcal cervicitis Approved [49]
Cocaine DMSOX7I Anaesthesia 9A78.6 Approved [49]
Gefitinib DM15F0X Colon adenocarcinoma Approved [6]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [52]
Lapatinib DM3BH1Y Breast cancer 2C60-2C65 Approved [6]
Crizotinib DM4F29C Non-small-cell lung cancer 2C25.Y Approved [6]
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Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas
Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Proto-oncogene c-Met (MET) TTNDSF4 MET_HUMAN Inhibitor [3]
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Inhibitor [3]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) Main DME DE4LYSA CP3A4_HUMAN Substrate [4]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [5]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Alanine aminotransferase 1 (GPT) OTOXOA0Q ALAT1_HUMAN Protein Interaction/Cellular Processes [6]
Hepatocyte growth factor receptor (MET) OT7K55MU MET_HUMAN Post-Translational Modifications [7]

References

1 Cabozantinib FDA Label
2 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: 5887).
3 Clinical pipeline report, company report or official report of Exelixis (2011).
4 Practical management of adverse events associated with cabozantinib treatment in patients with renal-cell carcinoma. Onco Targets Ther. 2017 Oct 19;10:5053-5064.
5 FDA Label of Cabozantinib. The 2020 official website of the U.S. Food and Drug Administration.
6 Cytotoxicity of 34 FDA approved small-molecule kinase inhibitors in primary rat and human hepatocytes. Toxicol Lett. 2018 Jul;291:138-148. doi: 10.1016/j.toxlet.2018.04.010. Epub 2018 Apr 12.
7 ROS-dependent DNA damage contributes to crizotinib-induced hepatotoxicity via the apoptotic pathway. Toxicol Appl Pharmacol. 2019 Nov 15;383:114768. doi: 10.1016/j.taap.2019.114768. Epub 2019 Oct 19.
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
9 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.
10 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
11 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
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. (Target id: 1815).
13 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
14 Beperminogene perplasmid for the treatment of critical limb ischemia. Expert Rev Cardiovasc Ther. 2014 Oct;12(10):1145-56.
15 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).
16 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
17 Preclinical overview of sorafenib, a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling.Mol Cancer Ther.2008 Oct;7(10):3129-40.
18 Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
19 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
20 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
21 A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22.
22 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
23 Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther. 2014;15(12):1635-45.
24 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
25 Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.
26 Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
27 Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
28 Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
29 Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
30 Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
31 Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
32 Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
33 The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
34 Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
35 Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys. 1997 Oct 1;346(1):161-9.
36 Tamoxifen inhibits cytochrome P450 2C9 activity in breast cancer patients. J Chemother. 2006 Aug;18(4):421-4.
37 Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology. 2003 Aug;144(8):3382-98.
38 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
39 Drug-drug interactions with imatinib: an observational study. Medicine (Baltimore). 2016 Oct;95(40):e5076.
40 Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30.
41 New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126.
42 A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat. 2003 Dec;82(3):191-7.
43 A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998 May;32(5):554-63.
44 Antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer positive for MET amplification. Mol Cancer Ther. 2012 Jul;11(7):1557-64. doi: 10.1158/1535-7163.MCT-11-0934. Epub 2012 Jun 22.
45 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
46 Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
47 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.
48 All-trans retinoic acid inhibits the cell proliferation but enhances the cell invasion through up-regulation of c-met in pancreatic cancer cells. Cancer Lett. 2005 Jun 28;224(2):303-10. doi: 10.1016/j.canlet.2004.10.016. Epub 2004 Dec 8.
49 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.
50 Quercetin protected against isoniazide-induced HepG2 cell apoptosis by activating the SIRT1/ERK pathway. J Biochem Mol Toxicol. 2019 Sep;33(9):e22369. doi: 10.1002/jbt.22369. Epub 2019 Jul 23.
51 Drug-induced liver injury: Oltipraz and C2-ceramide intervene HNF-1/GSTA1 expression via JNK signaling pathway. J Appl Toxicol. 2021 Dec;41(12):2011-2020. doi: 10.1002/jat.4181. Epub 2021 May 6.
52 A Study of Gentianae Radix et Rhizoma Class Differences Based on Chemical Composition and Core Efficacy. Molecules. 2023 Oct 17;28(20):7132. doi: 10.3390/molecules28207132.