Details of the Drug Combination

General Information of Drug Combination (ID: DC0H7KZ)

Drug Combination Name
Imiquimod Ingenol mebutate
Indication
Disease Entry Status REF
Keratosis, Actinic Phase 4 [1]
Component Drugs Imiquimod   DM1TMA3 Ingenol mebutate   DMK1CZJ
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 Imiquimod
Disease Entry ICD 11 Status REF
Alopecia areata ED70.2 Approved [2]
Condyloma 1A95 Approved [2]
Glioblastoma 2A00 Approved [2]
Melanoma 2C30 Approved [2]
Skin cancer 2C30-2C37 Approved [3]
Imiquimod Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Toll-like receptor 7 (TLR7) TTRJ1K4 TLR7_HUMAN Agonist [6]
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Imiquimod Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [7]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [7]
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Imiquimod Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Increases Secretion [8]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Secretion [8]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Secretion [8]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [9]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [9]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Increases Metabolism [10]
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⏷ Show the Full List of 6 DOT(s)
Indication(s) of Ingenol mebutate
Disease Entry ICD 11 Status REF
Actinic keratosis EK90.0 Approved [4]
Melanoma 2C30 Phase 3 [5]
Ingenol mebutate Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [11]
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Ingenol mebutate Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Protein S100-A4 (S100A4) OTLRGFSQ S10A4_HUMAN Decreases Expression [12]
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References

1 ClinicalTrials.gov (NCT02281682) IM Versus 5-FU Versus IMI Versus MAL-PDT in Treatment of Actinic Keratosis
2 Imiquimod FDA Label
3 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: 5003).
4 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: 7443).
5 ClinicalTrials.gov (NCT01546571) Study of a Melanoma Vaccine in Stage IIb, IIc, and III Melanoma Patients. U.S. National Institutes of Health.
6 Imiquimod enhances IFN-gamma production and effector function of T cells infiltrating human squamous cell carcinomas of the skin. J Invest Dermatol. 2009 Nov;129(11):2676-85.
7 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
8 Cannabidiol selectively modulates interleukin (IL)-1 and IL-6 production in toll-like receptor activated human peripheral blood monocytes. Toxicology. 2021 Dec;464:153016. doi: 10.1016/j.tox.2021.153016. Epub 2021 Nov 2.
9 Imiquimod induces apoptosis of human melanocytes. Arch Dermatol Res. 2010 May;302(4):301-6. doi: 10.1007/s00403-009-1012-0. Epub 2009 Dec 23.
10 The Toll-like receptor agonist imiquimod is metabolized by aryl hydrocarbon receptor-regulated cytochrome P450 enzymes in human keratinocytes and mouse liver. Arch Toxicol. 2019 Jul;93(7):1917-1926.
11 The skin cancer chemotherapeutic agent ingenol-3-angelate (PEP005) is a substrate for the epidermal multidrug transporter (ABCB1) and targets tumor vasculature. Cancer Res. 2010 Jun 1;70(11):4509-19.
12 Repurposing of ingenol mebutate for treating human colorectal cancer by targeting S100 calcium-binding protein A4 (S100A4). Toxicol Appl Pharmacol. 2022 Aug 15;449:116134. doi: 10.1016/j.taap.2022.116134. Epub 2022 Jun 18.