Details of the Drug Combination

General Information of Drug Combination (ID: DCNGTTW)

Drug Combination Name
Axitinib Aflibercept
Indication
Disease Entry Status REF
Neovascular Age-related Macular Degeneration Phase 1 [1]
Component Drugs Axitinib   DMGVH6N Aflibercept   DMT3D5I
Small molecular drug N.A.

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Axitinib
Disease Entry ICD 11 Status REF
Renal cell carcinoma 2C90 Approved [2]
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 [8]
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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 [9]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [9]
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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 [10]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [10]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [10]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [10]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [10]
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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 [11]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Affects Activity [12]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [13]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [13]
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Indication(s) of Aflibercept
Disease Entry ICD 11 Status REF
Central retinal vein occlusion with macular edema N.A. Approved [3]
Diabetic macular edema 9B71.02 Approved [4]
Exudative age-related macular degeneration 9B78.3Z Approved [5]
Metastasis from malignant tumor of colon N.A. Approved [6]
Metastatic colorectal cancer 2B91 Approved [7]
Aflibercept Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Vascular endothelial growth factor A (VEGFA) TTOHSBA VEGFA_HUMAN Modulator [7]
Vascular endothelial growth factor B (VEGFB) TTPJQHE VEGFB_HUMAN Modulator [7]
Placenta growth factor (PlGF) TT48I1Y PLGF_HUMAN Modulator [7]
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References

1 ClinicalTrials.gov (NCT04626128) Safety and Tolerability Study of Suprachoroidal Injection of CLS-AX Following Anti-VEGF Therapy in Neovascular AMD
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: 5659).
3 A review of neovascular glaucoma. Etiopathogenesis and treatment. Rom J Ophthalmol. 2021 Oct-Dec;65(4):315-329.
4 Aflibercept versus Faricimab in the Treatment of Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Review. Int J Mol Sci. 2022 Aug 20;23(16):9424.
5 Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend Regimens in Exudative Age-Related Macular Degeneration: 52- and 96-Week Findings from ALTAIR : A Randomized Controlled Trial. Adv Ther. 2020 Mar;37(3):1173-1187.
6 A Comparison of Folinic Acid, Fluorouracil and Irinotecan (FOLFIRI) plus Bevacizumab and FOLFIRI plus Aflibercept as Second-line Treatment for Metastatic Colorectal Cancer. Clin Oncol (R Coll Radiol). 2022 Aug;34(8):e323-e328.
7 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
8 Nat Rev Drug Discov. 2013 Feb;12(2):87-90.
9 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.
10 Clinical pharmacology of axitinib. Clin Pharmacokinet. 2013 Sep;52(9):713-25.
11 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.
12 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.
13 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.