Details of the Drug Combination

General Information of Drug Combination (ID: DC4BPE4)

Drug Combination Name
Lenvatinib Axitinib
Indication
Disease Entry Status REF
Advanced Renal Cell Carcinoma Phase 1 [1]
Component Drugs Lenvatinib   DMB1IU4 Axitinib   DMGVH6N
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Lenvatinib
Disease Entry ICD 11 Status REF
Thyroid cancer 2D10 Approved [2]
Thyroid gland follicular carcinoma N.A. Approved [3]
Thyroid gland papillary carcinoma N.A. Approved [3]
Hepatocellular carcinoma 2C12.02 Phase 3 [4]
Renal cell carcinoma 2C90 Phase 3 [5]
Melanoma 2C30 Phase 2 [4]
Solid tumour/cancer 2A00-2F9Z Phase 1/2 [5]
Ovarian cancer 2C73 Phase 1 [6]
Non-small-cell lung cancer 2C25.Y Application submitted [5]
Lenvatinib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Inhibitor [6]
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Lenvatinib Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
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Indication(s) of Axitinib
Disease Entry ICD 11 Status REF
Renal cell carcinoma 2C90 Approved [7]
Axitinib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Vascular endothelial growth factor receptor 2 (KDR) TTUTJGQ VGFR2_HUMAN Modulator [9]
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Axitinib Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [10]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [10]
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Axitinib Interacts with 5 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [11]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [11]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [11]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [11]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [11]
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Axitinib Interacts with 4 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Activity [12]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Affects Activity [13]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [14]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [14]
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References

1 ClinicalTrials.gov (NCT04522323) A Study to Evaluate MEDI5752 and Axitinib in Subjects With Advanced Renal Cell Carcinoma
2 FDA Approved Drug Products from FDA Official Website. 2018. Application Number: (ANDA) 208627.
3 Lenvatinib FDA Label
4 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 Emerging drugs for ovarian cancer. Expert Opin Emerg Drugs. 2008 Sep;13(3):523-36.
7 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: 5659).
8 Influence of CYP3A4/5 and ABC transporter polymorphisms on lenvatinib plasma trough concentrations in Japanese patients with thyroid cancer. Sci Rep. 2019 Apr 1;9(1):5404.
9 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
10 Meta-analysis of contribution of genetic polymorphisms in drug-metabolizing enzymes or transporters to axitinib pharmacokinetics. Eur J Clin Pharmacol. 2012 May;68(5):645-55.
11 Clinical pharmacology of axitinib. Clin Pharmacokinet. 2013 Sep;52(9):713-25.
12 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.
13 Identification of environmental chemicals that activate p53 signaling after in vitro metabolic activation. Arch Toxicol. 2022 Jul;96(7):1975-1987. doi: 10.1007/s00204-022-03291-5. Epub 2022 Apr 18.
14 MEK inhibition abrogates sunitinib resistance in a renal cell carcinoma patient-derived xenograft model. Br J Cancer. 2016 Oct 11;115(8):920-928. doi: 10.1038/bjc.2016.263. Epub 2016 Aug 25.