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

General Information of Drug (ID: DMMP3Y2)

Drug Name
YN-968D1 Drug Info
Synonyms Apatinib; Apatinib mesylate; VEGF receptor inhibitor (cancer), Advenchen; VEGFR2 receptor inhibitor (cancer), LSK/ Jiangsu Henrui/ Bukwang
Indication
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Approved [1]
Cross-matching ID
PubChem CID
45139106
CAS Number
CAS 1218779-75-9
TTD Drug ID
DMMP3Y2
VARIDT Drug ID
DR00819

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DTP
DOT
Drug Status:
Approved Drug(s)
Download the Complete Related Drug List
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 [5]
Romiplostim DM3U7SZ Thrombocytopenia 3B64 Approved [6]
Regorafenib DMHSY1I Gastrointestinal stromal tumour 2B5B Approved [7]
Sunitinib DMCBJSR Acute undifferentiated leukemia Approved [8]
Axitinib DMGVH6N Renal cell carcinoma 2C90 Approved [9]
Vandetanib DMRICNP Solid tumour/cancer 2A00-2F9Z Approved [10]
Pazopanib HCl DM6U9CQ Renal cell carcinoma 2C90 Approved [11]
Fruquintinib DMHOSCQ Colorectal cancer 2B91.Z Approved [12]
Cabozantinib DMIYDT4 Medullary thyroid gland carcinoma Approved [13]
Tivozanib DMUKC5L Renal cell carcinoma 2C90 Approved [14]
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Drug(s) Transported By Breast cancer resistance protein (ABCG2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [15]
Methotrexate DM2TEOL Anterior urethra cancer Approved [16]
Folic Acid DMEMBJC Colorectal carcinoma Approved [17]
Fluorouracil DMUM7HZ Adenocarcinoma 2D40 Approved [18]
Cisplatin DMRHGI9 Adenocarcinoma 2D40 Approved [19]
Progesterone DMUY35B Amenorrhea GA20.0 Approved [20]
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [21]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [20]
Sulfasalazine DMICA9H Irritable bowel syndrome DD91.0 Approved [22]
Imatinib DM7RJXL Acute lymphoblastic leukaemia 2A85 Approved [23]
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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 [24]
Ademetionine DMYQDBO Hepatic fibrosis DB93.0 Approved [25]
Theophylline DMRJFN9 Bronchitis CA20 Approved [26]
Rifampicin DM5DSFZ Non-insulin dependent diabetes 5A11 Approved [27]
Ethanol DMDRQZU Chronic pain MG30 Approved [28]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [29]
Phenobarbital DMXZOCG Cluster headache 8A81.0 Approved [30]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [31]
Didanosine DMI2QPE Human immunodeficiency virus infection 1C62 Approved [26]
Thioridazine DM35M8J Schizophrenia 6A20 Approved [32]
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Drug(s) Affected By Cytochrome P450 3A4 (CYP3A4)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Eplerenone DMF0NQR Heart failure BD10-BD13 Approved [33]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [34]
Isotretinoin DM4QTBN Acne vulgaris ED80 Approved [35]
Voriconazole DMAOL2S Aspergillosis 1F20 Approved [36]
Proguanil DMBL79I Malaria 1F40-1F45 Approved [37]
Ivermectin DMDBX5F Intestinal strongyloidiasis due to nematode parasite 1F6B Approved [37]
Loratadine DMF3AN7 Allergy 4A80-4A85 Approved [38]
Nelfinavir mesylate DMFX6G8 N. A. N. A. Approved [39]
Capsaicin DMGMF6V Back pain ME84.Z Approved [40]
Axitinib DMGVH6N Renal cell carcinoma 2C90 Approved [41]
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Drug(s) Affected By Cytochrome P450 2D6 (CYP2D6)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [42]
Paliperidone DM7NPJS Psychotic disorder 6A20-6A25 Approved [43]
Dopamine DMPGUCF Acromegaly 5A60.0 Approved [44]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [45]
Oxatomide DM1F42Z Hay fever CA08.00 Approved [46]
Cinacalcet DMCX0K3 Hyperparathyroidism 5A51 Approved [47]
Capsaicin DMGMF6V Back pain ME84.Z Approved [48]
Pentamidine DMHZJCG African trypanosomiasis 1F51 Approved [37]
Quinidine DMLPICK N. A. N. A. Approved [49]
Buprenorphine DMPRI8G Opioid dependence 6C43.2Z Approved [50]
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Drug(s) Affected By Cytochrome P450 2C9 (CYP2C9)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [34]
Troglitazone DM3VFPD Diabetic complication 5A2Y Approved [51]
Dapsone DM4LT8A Acne vulgaris ED80 Approved [37]
Voriconazole DMAOL2S Aspergillosis 1F20 Approved [36]
Capsaicin DMGMF6V Back pain ME84.Z Approved [48]
Zafirlukast DMHNQOG Asthma CA23 Approved [52]
Niclosamide DMJAGXQ Cestodes infection 1F70-1F76 Approved [37]
Eicosapentaenoic acid/docosa-hexaenoic acid DMMUCG4 Hypertriglyceridemia 5C80.1 Approved [53]
Fluconazole DMOWZ6B Cryptococcal meningitis Approved [36]
Quinine DMSWYF5 Malaria 1F40-1F45 Approved [37]
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Drug(s) Affected By Cytochrome P450 2B6 (CYP2B6)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Sertraline DM0FB1J Coronary heart disease BA80.Z Approved [54]
Ritonavir DMU764S Human immunodeficiency virus infection 1C62 Approved [55]
Rifampicin DM5DSFZ Non-insulin dependent diabetes 5A11 Approved [56]
Thalidomide DM70BU5 Adult T-cell leukemia/lymphoma Approved [57]
Phenytoin DMNOKBV Epilepsy 8A60-8A68 Approved [58]
Clopidogrel DMOL54H Acute coronary syndrome BA41 Approved [59]
Artemisinin DMOY7W3 Malaria 1F40-1F45 Approved [60]
Malathion DMXZ84M Pediculus capitis infestation 1G00.0 Approved [61]
Phenobarbital DMXZOCG Cluster headache 8A81.0 Approved [62]
Permethrin DMZ0Q1G Pediculus capitis infestation 1G00.0 Approved [63]
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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
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Inhibitor [2]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [3]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Cytochrome P450 2B6 (CYP2B6) OTOYO4S7 CP2B6_HUMAN Gene/Protein Processing [4]
Cytochrome P450 2C9 (CYP2C9) OTGLBN29 CP2C9_HUMAN Gene/Protein Processing [4]
Cytochrome P450 2D6 (CYP2D6) OTZJC802 CP2D6_HUMAN Gene/Protein Processing [4]
Cytochrome P450 2E1 (CYP2E1) OTHQ17JG CP2E1_HUMAN Gene/Protein Processing [4]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Gene/Protein Processing [4]

References

1 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: 7648).
2 YN968D1 is a novel and selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase with potent activity in vitro and in vivo. Cancer Sci. 2011 Jul;102(7):1374-80.
3 Apatinib (YN968D1) reverses multidrug resistance by inhibiting the efflux function of multiple ATP-binding cassette transporters. Cancer Res. 2010 Oct 15;70(20):7981-91.
4 Evaluation of the inhibition effects of apatinib on human and rat cytochrome P450. Toxicol Lett. 2018 Nov;297:1-7.
5 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.
6 Anthranilic acid amides: a novel class of antiangiogenic VEGF receptor kinase inhibitors. J Med Chem. 2002 Dec 19;45(26):5687-93.
7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
8 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
9 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
10 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.
11 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
12 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.
13 Clinical pipeline report, company report or official report of Exelixis (2011).
14 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services
15 Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
16 Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
17 The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
18 Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
19 Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
20 Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
21 The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
22 Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
23 Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
24 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.
25 Inhibition of CYP2E1 catalytic activity in vitro by S-adenosyl-L-methionine. Biochem Pharmacol. 2005 Apr 1;69(7):1081-93.
26 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.
27 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.
28 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.
29 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
30 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.
31 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.
32 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.
33 The relative role of CYP3A4 and CYP3A5 in eplerenone metabolism. Toxicol Lett. 2019 Oct 15;315:9-13.
34 Characterization of the structural determinants required for potent mechanism-based inhibition of human cytochrome P450 1A1 by cannabidiol. Chem Biol Interact. 2014 May 25;215:62-8.
35 Retinoids activate the RXR/SXR-mediated pathway and induce the endogenous CYP3A4 activity in Huh7 human hepatoma cells. Toxicol Sci. 2006 Jul;92(1):51-60.
36 The novel azole R126638 is a selective inhibitor of ergosterol synthesis in Candida albicans, Trichophyton spp., and Microsporum canis. Antimicrob Agents Chemother. 2004 Sep;48(9):3272-8.
37 Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s. Drug Metab Dispos. 2001 Jan;29(1):30-5.
38 Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity. Bioorg Med Chem Lett. 2004 Nov 15;14(22):5591-4.
39 Mechanism-based inactivation of CYP3A by HIV protease inhibitors. J Pharmacol Exp Ther. 2005 Feb;312(2):583-91.
40 Studies of the toxicological potential of capsinoids, XIII: inhibitory effects of capsaicin and capsinoids on cytochrome P450 3A4 in human liver microsomes. Int J Toxicol. 2010 Mar;29(2 Suppl):22S-6S.
41 Investigation of the effects of axitinib on the pharmacokinetics of loperamide and its main metabolite N-demethylated loperamide in rats by UPLC-MS/MS. Chem Biol Interact. 2019 Sep 1;310:108744. doi: 10.1016/j.cbi.2019.108744. Epub 2019 Jul 9.
42 Human recombinant cytochrome P450 enzymes display distinct hydrogen peroxide generating activities during substrate independent NADPH oxidase reactions. Toxicol Sci. 2014 Oct;141(2):344-52. doi: 10.1093/toxsci/kfu133. Epub 2014 Jul 24.
43 Cytochrome P450 2D6 genotype and steady state plasma levels of risperidone and 9-hydroxyrisperidone. Psychopharmacology (Berl). 1999 Dec;147(3):300-5. doi: 10.1007/s002130051171.
44 Effect of penicillin-based antibiotics, amoxicillin, ampicillin, and piperacillin, on drug-metabolizing activities of human hepatic cytochromes P450. J Toxicol Sci. 2016 Feb;41(1):143-6.
45 Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos. 2011 Nov;39(11):2049-56. doi: 10.1124/dmd.111.041384. Epub 2011 Aug 5.
46 Identification of human P450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its kinetic parameters and inhibition constants. Biol Pharm Bull. 2005 Feb;28(2):328-34.
47 Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl. Eur J Clin Pharmacol. 2007 Feb;63(2):159-63.
48 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.
49 Inhibition of cytochrome P4502D6 activity with paroxetine normalizes the ultrarapid metabolizer phenotype as measured by nortriptyline pharmacokinetics and the debrisoquin test. Clin Pharmacol Ther. 2001 Oct;70(4):327-35.
50 Interaction of buprenorphine and its metabolite norbuprenorphine with cytochromes p450 in vitro. Drug Metab Dispos. 2003 Jun;31(6):768-72.
51 Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition. Drug Metab Dispos. 2003 Apr;31(4):439-46.
52 Potential of pranlukast and zafirlukast in the inhibition of human liver cytochrome P450 enzymes. Xenobiotica. 2004 May;34(5):429-38.
53 The inhibitory effect of polyunsaturated fatty acids on human CYP enzymes. Life Sci. 2006 Nov 25;79(26):2432-40.
54 Cytochrome P450 inhibition potential of new psychoactive substances of the tryptamine class. Toxicol Lett. 2016 Jan 22;241:82-94.
55 Transcriptional profiling suggests that Nevirapine and Ritonavir cause drug induced liver injury through distinct mechanisms in primary human hepatocytes. Chem Biol Interact. 2016 Aug 5;255:31-44.
56 Evaluation of gene induction of drug-metabolizing enzymes and transporters in primary culture of human hepatocytes using high-sensitivity real-time reverse transcription PCR. Yakugaku Zasshi. 2002 May;122(5):339-61.
57 Thalidomide increases human hepatic cytochrome P450 3A enzymes by direct activation of the pregnane X receptor. Chem Res Toxicol. 2014 Feb 17;27(2):304-308.
58 Human constitutive androstane receptor mediates induction of CYP2B6 gene expression by phenytoin. J Biol Chem. 2004 Jul 9;279(28):29295-301. doi: 10.1074/jbc.M400580200. Epub 2004 Apr 28.
59 Identification of novel agonists by high-throughput screening and molecular modelling of human constitutive androstane receptor isoform 3. Arch Toxicol. 2019 Aug;93(8):2247-2264. doi: 10.1007/s00204-019-02495-6. Epub 2019 Jul 16.
60 Antimalarial artemisinin drugs induce cytochrome P450 and MDR1 expression by activation of xenosensors pregnane X receptor and constitutive androstane receptor. Mol Pharmacol. 2005 Jun;67(6):1954-65.
61 Characterization of human cytochrome P450 induction by pesticides. Toxicology. 2012 Mar 29;294(1):17-26.
62 Species-specific mechanisms for cholesterol 7alpha-hydroxylase (CYP7A1) regulation by drugs and bile acids. Arch Biochem Biophys. 2005 Feb 1;434(1):75-85.
63 Pyrethroids: cytotoxicity and induction of CYP isoforms in human hepatocytes. Drug Metabol Drug Interact. 2008;23(3-4):211-36.