Details of the Drug Combination

General Information of Drug Combination (ID: DCDB55G)

Drug Combination Name
Brincidofovir Probenecid
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Brincidofovir   DMS0PND Probenecid   DMMFWOJ
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: 2.85
Bliss Independence Score: 2.85
Loewe Additivity Score: 3.39
LHighest Single Agent (HSA) Score: 3.46

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Brincidofovir
Disease Entry ICD 11 Status REF
Coronavirus Disease 2019 (COVID-19) 1D6Y Investigative [2]
Indication(s) of Probenecid
Disease Entry ICD 11 Status REF
Acute gonococcal cervicitis N.A. Approved [3]
Gout FA25 Approved [4]
Hyperuricaemia 5C55.Y Approved [4]
Probenecid Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Solute carrier family 22 member 8 (SLC22A8) TTTQR47 S22A8_HUMAN Blocker [6]
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Probenecid Interacts with 3 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [7]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [8]
Monocarboxylate transporter 6 (SLC16A5) DT3I124 MOT6_HUMAN Substrate [9]
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Probenecid Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [10]
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Probenecid Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Taste receptor type 2 member 38 (TAS2R38) OTX5MM36 T2R38_HUMAN Decreases Activity [11]
Taste receptor type 2 member 43 (TAS2R43) OT70V8MZ T2R43_HUMAN Decreases Activity [11]
Solute carrier family 22 member 6 (SLC22A6) OTKRCBVM S22A6_HUMAN Decreases Activity [12]
Organic anion transporter 7 (SLC22A9) OTO4BJCC S22A9_HUMAN Decreases Activity [12]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [13]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [13]
Organic anion transporter 3 (SLC22A8) OT8BY933 S22A8_HUMAN Decreases Expression [14]
Solute carrier family 22 member 12 (SLC22A12) OT72ZAWS S22AC_HUMAN Affects Activity [15]
Solute carrier family 22 member 11 (SLC22A11) OTAJLNJZ S22AB_HUMAN Decreases Activity [16]
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⏷ Show the Full List of 9 DOT(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 A rational roadmap for SARS-CoV-2/COVID-19 pharmacotherapeutic research and development: IUPHAR Review 29. Br J Pharmacol. 2020 May 1;10.1111/bph.15094.
3 Probenecid 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: 4357).
5 Carboxylic acid drug-induced DNA nicking in HEK293 cells expressing human UDP-glucuronosyltransferases: role of acyl glucuronide metabolites and glycation pathways. Chem Res Toxicol. 2007 Oct;20(10):1520-7. doi: 10.1021/tx700188x. Epub 2007 Sep 20.
6 Transport of organic anions across the basolateral membrane of proximal tubule cells. Rev Physiol Biochem Pharmacol. 2003;146:95-158.
7 MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both processes are stimulated by probenecid. Int J Cancer. 2005 Sep 20;116(5):824-9.
8 Characterization of the efflux transport of 17beta-estradiol-D-17beta-glucuronide from the brain across the blood-brain barrier. J Pharmacol Exp Ther. 2001 Jul;298(1):316-22.
9 Quercetin, Morin, Luteolin, and Phloretin Are Dietary Flavonoid Inhibitors of Monocarboxylate Transporter 6. Mol Pharm. 2017 Sep 5;14(9):2930-2936.
10 Modulation of 3'-azido-3'-deoxythymidine catabolism by probenecid and acetaminophen in freshly isolated rat hepatocytes. Biochem Pharmacol. 1991 Sep 12;42(7):1475-80.
11 Probenecid inhibits the human bitter taste receptor TAS2R16 and suppresses bitter perception of salicin. PLoS One. 2011;6(5):e20123.
12 Inhibition of organic anion transporter (OAT) activity by cigarette smoke condensate. Toxicol In Vitro. 2017 Oct;44:27-35.
13 Evaluation and mechanistic analysis of the cytotoxicity of the acyl glucuronide of nonsteroidal anti-inflammatory drugs. Drug Metab Dispos. 2014 Jan;42(1):1-8. doi: 10.1124/dmd.113.054478. Epub 2013 Oct 8.
14 Targeting organic anion transporter 3 with probenecid as a novel anti-influenza a virus strategy. Antimicrob Agents Chemother. 2013 Jan;57(1):475-83. doi: 10.1128/AAC.01532-12. Epub 2012 Nov 5.
15 Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion. J Am Soc Nephrol. 2004 Jan;15(1):164-73. doi: 10.1097/01.asn.0000105320.04395.d0.
16 Neonicotinoid pesticides poorly interact with human drug transporters. J Biochem Mol Toxicol. 2019 Oct;33(10):e22379. doi: 10.1002/jbt.22379. Epub 2019 Jul 31.