Details of the Drug Combination

General Information of Drug Combination (ID: DCPBTVW)

Drug Combination Name
Tosyl-l-arginine methyl ester Selumetinib
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs Tosyl-l-arginine methyl ester   DMONGIR Selumetinib   DMC7W6R
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: DIPG25
Zero Interaction Potency (ZIP) Score: 4.963
Bliss Independence Score: 9.804
Loewe Additivity Score: 1.881
LHighest Single Agent (HSA) Score: 2.432

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Tosyl-l-arginine methyl ester
Disease Entry ICD 11 Status REF
Solid tumour/cancer 2A00-2F9Z Preclinical [2]
Tosyl-l-arginine methyl ester Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Cell division cycle protein 20 homolog (CDC20) TTBKFDV CDC20_HUMAN Inhibitor [9]
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Indication(s) of Selumetinib
Disease Entry ICD 11 Status REF
Neurofibromatosis type 1 LD2D.10 Approved [3]
Melanoma 2C30 Phase 3 [4]
Thyroid cancer 2D10 Phase 3 [5]
Non-small-cell lung cancer 2C25.Y Phase 2 [6]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [7]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [7]
Solid tumour/cancer 2A00-2F9Z Investigative [8]
Selumetinib Interacts with 5 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
MAPK/ERK kinase kinase (MAP3K) TTROQ37 NOUNIPROTAC Modulator [10]
ERK activator kinase 1 (MEK1) TTIDAPM MP2K1_HUMAN Inhibitor [5]
ERK activator kinase 2 (MEK2) TTTW2NY MP2K2_HUMAN Inhibitor [5]
HUMAN ERK activator kinase 1 (MEK1) TTAW3TO MP2K1_HUMAN Inhibitor [7]
HUMAN ERK activator kinase 2 (MEK2) TTWX403 MP2K2_HUMAN Inhibitor [7]
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Selumetinib 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 [11]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Decreases Phosphorylation [12]
Interstitial collagenase (MMP1) OTI4I2V1 MMP1_HUMAN Decreases Activity [12]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Activity [12]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Decreases Activity [12]
Cyclic AMP-responsive element-binding protein 1 (CREB1) OT1MDLA1 CREB1_HUMAN Decreases Phosphorylation [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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⏷ Show the Full List of 8 DOT(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
2 Emerging therapies targeting the ubiquitin proteasome system in cancer. J Clin Invest. 2014 Jan;124(1):6-12.
3 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
4 ClinicalTrials.gov (NCT01933932) Assess Efficacy & Safety of Selumetinib in Combination With Docetaxel in Patients Receiving 2nd Line Treatment for v-Ki-ras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Positive NSCLC (SELECT-1)
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: 5665).
7 Coronaviruses - drug discovery and therapeutic options. Nat Rev Drug Discov. 2016 May;15(5):327-47.
8 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. (Target id: 1479).
9 Targeting Cdc20 as a novel cancer therapeutic strategy. Pharmacol Ther. 2015 Jul;151:141-51.
10 Intrinsic resistance to selumetinib, a selective inhibitor of MEK1/2, by cAMP-dependent protein kinase A activation in human lung and colorectal cancer cells.Br J Cancer.2012 May 8;106(10):1648-59.
11 Antitumor action of the MET tyrosine kinase inhibitor crizotinib (PF-02341066) in gastric cancer positive for MET amplification. Mol Cancer Ther. 2012 Jul;11(7):1557-64. doi: 10.1158/1535-7163.MCT-11-0934. Epub 2012 Jun 22.
12 Ursonic acid exerts inhibitory effects on matrix metalloproteinases via ERK signaling pathway. Chem Biol Interact. 2020 Jan 5;315:108910. doi: 10.1016/j.cbi.2019.108910. Epub 2019 Nov 29.
13 The synergistic interaction of MEK and PI3K inhibitors is modulated by mTOR inhibition. Br J Cancer. 2012 Apr 10;106(8):1386-94. doi: 10.1038/bjc.2012.70. Epub 2012 Mar 13.