Details of the Drug Combination

General Information of Drug Combination (ID: DCAO0E8)

Drug Combination Name
Imiquimod LDE225
Indication
Disease Entry Status REF
Basal Cell Carcinoma Phase 2 [1]
Component Drugs Imiquimod   DM1TMA3 LDE225   DMM9F25
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 [7]
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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 [8]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [8]
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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 [9]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Secretion [9]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Secretion [9]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [10]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [10]
Cytochrome P450 2C19 (CYP2C19) OTFMJYYE CP2CJ_HUMAN Increases Metabolism [11]
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⏷ Show the Full List of 6 DOT(s)
Indication(s) of LDE225
Disease Entry ICD 11 Status REF
Basal cell carcinoma 2C32 Approved [4]
Medulloblastoma 2A00.10 Phase 2 [5]
Skin cancer 2C30-2C37 Phase 2 [6]
LDE225 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Smoothened homolog (SMO) TT8J1S3 SMO_HUMAN Modulator [12]
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LDE225 Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Suppressor of fused homolog (SUFU) OT0IRYG1 SUFU_HUMAN Decreases Response To Substance [13]
Zinc finger protein GLI2 (GLI2) OTIRV97L GLI2_HUMAN Decreases Response To Substance [13]
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References

1 ClinicalTrials.gov (NCT03534947) A Study to Evaluate Neoadjuvant Sonidegib Followed by Surgery or Imiquimod in the Management of Basal Cell Carcinoma
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 The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma. J Am Acad Dermatol. 2016 Jul;75(1):113-125.e5.
5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
6 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: 8199).
7 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.
8 Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
9 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.
10 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.
11 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.
12 Inhibition of Hedgehog signalling by NVP-LDE225 (Erismodegib) interferes with growth and invasion of human renal cell carcinoma cells. Br J Cancer. 2014 Sep 9;111(6):1168-79.
13 Epigenetic targeting of Hedgehog pathway transcriptional output through BET bromodomain inhibition. Nat Med. 2014 Jul;20(7):732-40. doi: 10.1038/nm.3613. Epub 2014 Jun 29.