Details of the Drug Combination

General Information of Drug Combination (ID: DCL1OQV)

Drug Combination Name
AZD8055 Trametinib
Indication
Disease Entry Status REF
Glioblastoma Investigative [1]
Component Drugs AZD8055   DM7L8SG Trametinib   DM2JGQ3
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: JHH-136
Zero Interaction Potency (ZIP) Score: 52.02
Bliss Independence Score: 57.078
Loewe Additivity Score: 18.255
LHighest Single Agent (HSA) Score: 26.542

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of AZD8055
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Discontinued in Phase 1/2 [2]
AZD8055 Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Serine/threonine-protein kinase mTOR (mTOR) TTCJG29 MTOR_HUMAN Inhibitor [6]
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Indication(s) of Trametinib
Disease Entry ICD 11 Status REF
Melanoma 2C30 Approved [3]
Metastatic melanoma 2E2Z Approved [4]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [5]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [5]
Trametinib Interacts with 3 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
MAPK/ERK kinase kinase (MAP3K) TTROQ37 NOUNIPROTAC Modulator [7]
HUMAN ERK activator kinase 1 (MEK1) TTAW3TO MP2K1_HUMAN Inhibitor [5]
HUMAN ERK activator kinase 2 (MEK2) TTWX403 MP2K2_HUMAN Inhibitor [5]
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Trametinib Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Increases Expression [8]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [8]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Phosphorylation [8]
Tumor necrosis factor receptor superfamily member 16 (NGFR) OTPKSM49 TNR16_HUMAN Increases Expression [9]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [8]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [8]
Guanine nucleotide-binding protein subunit alpha-11 (GNA11) OT0K99TO GNA11_HUMAN Increases Response To Substance [8]
Guanine nucleotide-binding protein G(q) subunit alpha (GNAQ) OTOODWTU GNAQ_HUMAN Increases Response To Substance [8]
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⏷ Show the Full List of 8 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Embryonal rhabdomyosarcoma DCAJRS9 CTR Investigative [1]
Embryonal rhabdomyosarcoma DCZQ41N RD Investigative [1]
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References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
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: 7714).
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: 6495).
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
5 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
6 Clinical pipeline report, company report or official report of AstraZeneca (2009).
7 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
8 Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner. Clin Cancer Res. 2012 Aug 15;18(16):4345-55. doi: 10.1158/1078-0432.CCR-11-3227. Epub 2012 Jun 25.
9 Harnessing autophagy to overcome mitogen-activated protein kinase kinase inhibitor-induced resistance in metastatic melanoma. Br J Dermatol. 2019 Feb;180(2):346-356. doi: 10.1111/bjd.17333. Epub 2018 Nov 25.