Details of the Drug Combination

General Information of Drug Combination (ID: DCW008H)

Drug Combination Name
BRL-15572 Oseltamivir
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs BRL-15572   DMM61Y2 Oseltamivir   DMGO72P
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 21.05
Bliss Independence Score: 21.05
Loewe Additivity Score: 36.52
LHighest Single Agent (HSA) Score: 36.52

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of BRL-15572
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [2]
BRL-15572 Interacts with 9 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
5-HT 1B receptor (HTR1B) TTK8CXU 5HT1B_HUMAN Agonist [6]
5-HT 1D receptor (HTR1D) TT6MSOK 5HT1D_HUMAN Agonist [6]
5-HT 6 receptor (HTR6) TTJS8PY 5HT6R_HUMAN Agonist [6]
5-HT 2B receptor (HTR2B) TT0K1SC 5HT2B_HUMAN Agonist [6]
5-HT 2A receptor (HTR2A) TTJQOD7 5HT2A_HUMAN Agonist [6]
5-HT 1F receptor (HTR1F) TT0MI3F 5HT1F_HUMAN Agonist [6]
5-HT 1A receptor (HTR1A) TTSQIFT 5HT1A_HUMAN Agonist [6]
5-HT 2C receptor (HTR2C) TTWJBZ5 5HT2C_HUMAN Agonist [6]
5-HT 1E receptor (HTR1E) TTCPG9S 5HT1E_HUMAN Agonist [6]
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⏷ Show the Full List of 9 DTT(s)
Indication(s) of Oseltamivir
Disease Entry ICD 11 Status REF
Influenza 1E30-1E32 Approved [3]
Influenza virus infection 1E30-1E32 Approved [4]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [5]
Oseltamivir Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Influenza Neuraminidase (Influ NA) TT50QJ3 NRAM_I33A0 Inhibitor [7]
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Oseltamivir Interacts with 5 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [8]
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [9]
Peptide transporter 1 (SLC15A1) DT9G7XN S15A1_HUMAN Substrate [10]
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [11]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [11]
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Oseltamivir Interacts with 3 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Cystine/glutamate transporter (SLC7A11) OTKJ6PXW XCT_HUMAN Decreases Expression [12]
Liver carboxylesterase 1 (CES1) OT9L0LR8 EST1_HUMAN Increases Metabolism [13]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Response To Substance [14]
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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 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: 10).
3 Oseltamivir FDA Label
4 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
5 ClinicalTrials.gov (NCT04261270) A Randomized,Open,Controlled Clinical Study to Evaluate the Efficacy of ASC09F and Ritonavir for 2019-nCoV Pneumonia
6 SB-216641 and BRL-15572--compounds to pharmacologically discriminate h5-HT1B and h5-HT1D receptors. Naunyn Schmiedebergs Arch Pharmacol. 1997 Sep;356(3):312-20.
7 Current and future antiviral therapy of severe seasonal and avian influenza. Antiviral Res. 2008 Apr;78(1):91-102.
8 Nonclinical pharmacokinetics of oseltamivir and oseltamivir carboxylate in the central nervous system. Antimicrob Agents Chemother. 2009 Nov;53(11):4753-61.
9 Limited brain distribution of [3R,4R,5S]-4-acetamido-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (Ro 64-0802), a pharmacologically active form of oseltamivir, by active efflux across the blood-brain barrier mediated by organic anion transporter 3 (Oat3/Slc22a8) and multidrug resistance-associated protein 4 (Mrp4/Abcc4). Drug Metab Dispos. 2009 Feb;37(2):315-21.
10 Oseltamivir (tamiflu) is a substrate of peptide transporter 1. Drug Metab Dispos. 2009 Aug;37(8):1676-81.
11 FDA Drug Development and Drug Interactions
12 An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
13 In vitro inhibition of carboxylesterase 1 by Kava (Piper methysticum) Kavalactones. Chem Biol Interact. 2022 Apr 25;357:109883. doi: 10.1016/j.cbi.2022.109883. Epub 2022 Mar 9.
14 Interleukin-6 alters the cellular responsiveness to clopidogrel, irinotecan, and oseltamivir by suppressing the expression of carboxylesterases HCE1 and HCE2. Mol Pharmacol. 2007 Sep;72(3):686-94. doi: 10.1124/mol.107.036889. Epub 2007 May 30.