Details of the Drug Combination

General Information of Drug Combination (ID: DCUU9QF)

Drug Combination Name
Tosyl-l-arginine methyl ester Erlotinib
Indication
Disease Entry Status REF
Diffuse intrinsic pontine glioma Investigative [1]
Component Drugs Tosyl-l-arginine methyl ester   DMONGIR Erlotinib   DMCMBHA
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: 1.72
Bliss Independence Score: 9.65
Loewe Additivity Score: 1.3
LHighest Single Agent (HSA) Score: 1.91

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 [5]
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Indication(s) of Erlotinib
Disease Entry ICD 11 Status REF
Adrenal gland neoplasm N.A. Approved [3]
Adult hepatocellular carcinoma N.A. Approved [3]
Brain cancer 2A00 Approved [3]
Esophageal disorder N.A. Approved [3]
Lung cancer 2C25.0 Approved [3]
Non-small-cell lung cancer 2C25.Y Approved [4]
Pancreatic adenocarcinoma N.A. Approved [3]
Psoriasis EA90 Approved [3]
Salivary gland squamous cell carcinoma N.A. Approved [3]
Pancreatic cancer 2C10 Phase 3 [4]
Colon cancer 2B90.Z Phase 2 [4]
Ependymoma 2A00.0Y Investigative [3]
Neoplastic meningitis N.A. Investigative [3]
Neuroblastoma 2D11.2 Investigative [3]
Erlotinib Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Epidermal growth factor receptor (EGFR) TTGKNB4 EGFR_HUMAN Inhibitor [6]
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Erlotinib Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [8]
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Erlotinib Interacts with 4 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [10]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [10]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [10]
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Erlotinib Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Epidermal growth factor receptor (EGFR) OTAPLO1S EGFR_HUMAN Increases Response [11]
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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 Erlotinib FDA Label
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: 4920).
5 Targeting Cdc20 as a novel cancer therapeutic strategy. Pharmacol Ther. 2015 Jul;151:141-51.
6 Quantitative prediction of fold resistance for inhibitors of EGFR. Biochemistry. 2009 Sep 8;48(35):8435-48.
7 Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on erlotinib hydrochloride (Tarceva) disposition in in vitro and in vivo pharmacokinetic studies employing Bcrp1-/-/Mdr1a/1b-/- (triple-knockout) and wild-type mice. Mol Cancer Ther. 2008 Aug;7(8):2280-7.
8 Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy. Adv Drug Deliv Rev. 2009 Jan 31;61(1):26-33.
9 In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug Metab Dispos. 2014 Jul;42(7):1202-9.
10 Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706.
11 Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004 May 20;350(21):2129-39. doi: 10.1056/NEJMoa040938. Epub 2004 Apr 29.