Details of the Drug Combination

General Information of Drug Combination (ID: DC58PAT)

Drug Combination Name
Trametinib Prazosin
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs Trametinib   DM2JGQ3 Prazosin   DMCD9YG
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: SU-DIPG-XIII
Zero Interaction Potency (ZIP) Score: 9.072
Bliss Independence Score: 9.243
Loewe Additivity Score: 3.645
LHighest Single Agent (HSA) Score: 5.764

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Trametinib
Disease Entry ICD 11 Status REF
Melanoma 2C30 Approved [2]
Metastatic melanoma 2E2Z Approved [3]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [4]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [4]
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 [6]
HUMAN ERK activator kinase 1 (MEK1) TTAW3TO MP2K1_HUMAN Inhibitor [4]
HUMAN ERK activator kinase 2 (MEK2) TTWX403 MP2K2_HUMAN Inhibitor [4]
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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 [7]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Decreases Expression [7]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Phosphorylation [7]
Tumor necrosis factor receptor superfamily member 16 (NGFR) OTPKSM49 TNR16_HUMAN Increases Expression [8]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [7]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [7]
Guanine nucleotide-binding protein subunit alpha-11 (GNA11) OT0K99TO GNA11_HUMAN Increases Response To Substance [7]
Guanine nucleotide-binding protein G(q) subunit alpha (GNAQ) OTOODWTU GNAQ_HUMAN Increases Response To Substance [7]
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⏷ Show the Full List of 8 DOT(s)
Indication(s) of Prazosin
Disease Entry ICD 11 Status REF
Benign prostatic hyperplasia GA90 Approved [3]
Congestive heart failure BD10 Approved [3]
Hypertension BA00-BA04 Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 2 [5]
Prazosin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adrenergic receptor Alpha-1 (ADRA1) TTG28O6 NOUNIPROTAC Antagonist [9]
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Prazosin Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [10]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [11]
Organic cation transporter 1 (SLC22A1) DTT79CX S22A1_HUMAN Substrate [12]
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Prazosin Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A1 (CYP1A1) DE6OQ3W CP1A1_HUMAN Metabolism [13]
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References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125976
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: 6495).
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
5 Prazosin to Prevent COVID-19 (PREVENT-COVID Trial) (PREVENT)
6 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
7 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.
8 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.
9 Adventitia removal does not modify the alphaID-adrenoceptors response in aorta during hypertension and ageing. Auton Autacoid Pharmacol. 2009 Jul;29(3):117-33.
10 Evidence for two nonidentical drug-interaction sites in the human P-glycoprotein. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10594-9.
11 P-glycoprotein and breast cancer resistance protein expression and function at the blood-brain barrier and blood-cerebrospinal fluid barrier (choroid plexus) in streptozotocin-induced diabetes in rats. Brain Res. 2011 Jan 25;1370:238-45.
12 Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett. 2006 Mar 8;234(1):4-33.
13 Role of adrenoceptor-linked signaling pathways in the regulation of CYP1A1 gene expression. Biochem Pharmacol. 2005 Jan 15;69(2):277-87.