General Information of Drug Combination (ID: DCROF6W)

Drug Combination Name
Probenecid Lefaxin
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Probenecid   DMMFWOJ Lefaxin   DM0CEY3
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 5.48
Bliss Independence Score: 5.48
Loewe Additivity Score: 18.56
LHighest Single Agent (HSA) Score: 18.57

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Probenecid
Disease Entry ICD 11 Status REF
Acute gonococcal cervicitis N.A. Approved [2]
Gout FA25 Approved [3]
Hyperuricaemia 5C55.Y Approved [3]
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 13 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Increases Activity [11]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Decreases Activity [12]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Expression [13]
Taste receptor type 2 member 38 (TAS2R38) OTX5MM36 T2R38_HUMAN Decreases Activity [14]
Taste receptor type 2 member 43 (TAS2R43) OT70V8MZ T2R43_HUMAN Decreases Activity [14]
Solute carrier family 22 member 6 (SLC22A6) OTKRCBVM S22A6_HUMAN Decreases Activity [15]
Organic anion transporter 7 (SLC22A9) OTO4BJCC S22A9_HUMAN Decreases Activity [15]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [16]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [16]
Sodium-coupled monocarboxylate transporter 1 (SLC5A8) OTA0WELF SC5A8_HUMAN Decreases Activity [17]
Organic anion transporter 3 (SLC22A8) OT8BY933 S22A8_HUMAN Decreases Expression [18]
Solute carrier family 22 member 12 (SLC22A12) OT72ZAWS S22AC_HUMAN Affects Activity [19]
Solute carrier family 22 member 11 (SLC22A11) OTAJLNJZ S22AB_HUMAN Decreases Activity [20]
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⏷ Show the Full List of 13 DOT(s)
Indication(s) of Lefaxin
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [4]
Lefaxin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Coagulation factor Xa (F10) TTCIHJA FA10_HUMAN Inhibitor [4]
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Lefaxin Interacts with 11 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Acetylcholinesterase (ACHE) OT2H8HG6 ACES_HUMAN Decreases Activity [21]
Superoxide dismutase (SOD1) OT39TA1L SODC_HUMAN Affects Expression [22]
Catalase (CAT) OTHEBX9R CATA_HUMAN Decreases Expression [22]
Superoxide dismutase , mitochondrial (SOD2) OTIWXGZ9 SODM_HUMAN Decreases Expression [22]
Glutathione peroxidase 1 (GPX1) OTE2O72Q GPX1_HUMAN Decreases Expression [22]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Decreases Expression [22]
DNA cytosine-5)-methyltransferase 1 (DNMT1) OTM2DGTK DNMT1_HUMAN Decreases Expression [22]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Decreases Expression [22]
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Decreases Expression [22]
Caspase-8 (CASP8) OTA8TVI8 CASP8_HUMAN Decreases Expression [22]
Albumin (ALB) OTVMM513 ALBU_HUMAN Affects Binding [23]
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⏷ Show the Full List of 11 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 Probenecid FDA Label
3 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).
4 Novel approaches to the treatment of thrombosis. Trends Pharmacol Sci. 2002 Jan;23(1):25-32.
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 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. doi: 10.1002/ijc.21013.
12 Mercury induces multidrug resistance-associated protein gene through p38 mitogen-activated protein kinase. Toxicol Lett. 2005 Jan 15;155(1):143-50. doi: 10.1016/j.toxlet.2004.09.007.
13 Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. Drug Metab Dispos. 2006 Oct;34(10):1742-8.
14 Probenecid inhibits the human bitter taste receptor TAS2R16 and suppresses bitter perception of salicin. PLoS One. 2011;6(5):e20123.
15 Inhibition of organic anion transporter (OAT) activity by cigarette smoke condensate. Toxicol In Vitro. 2017 Oct;44:27-35.
16 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.
17 The human tumour suppressor gene SLC5A8 expresses a Na+-monocarboxylate cotransporter. J Physiol. 2004 Jun 15;557(Pt 3):719-31. doi: 10.1113/jphysiol.2004.063859. Epub 2004 Apr 16.
18 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.
19 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.
20 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.
21 In vitro kinetic interactions of DEET, pyridostigmine and organophosphorus pesticides with human cholinesterases. Chem Biol Interact. 2011 Apr 25;190(2-3):79-83.
22 The Val16Ala-SOD2 polymorphism affects cyto-genotoxicity of pyridostigmine bromide on human peripheral blood mononuclear cells. Toxicol In Vitro. 2019 Oct;60:237-244.
23 Binding of pyridostigmine bromide, N,N-diethyl-m-toluamide and permethrin, alone and in combinations, to human serum albumin. Arch Toxicol. 2002 May;76(4):203-8. doi: 10.1007/s00204-002-0328-8. Epub 2002 Mar 9.