General Information of Drug Combination (ID: DCCD5T7)

Drug Combination Name
Emetine Probenecid
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Emetine   DMCT2YF Probenecid   DMMFWOJ
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: 9.43
Bliss Independence Score: 9.43
Loewe Additivity Score: 10.98
LHighest Single Agent (HSA) Score: 11.01

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Emetine
Disease Entry ICD 11 Status REF
Hepatitis virus infection 1E50-1E51 Approved [2]
Emetine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [6]
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Emetine Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [7]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [7]
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Emetine Interacts with 15 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) OT9QIHEQ RECK_HUMAN Decreases Expression [8]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Activity [9]
N-myc proto-oncogene protein (MYCN) OTWD33K1 MYCN_HUMAN Increases Degradation [10]
72 kDa type IV collagenase (MMP2) OT5NIWA2 MMP2_HUMAN Decreases Expression [8]
Interleukin-6 receptor subunit alpha (IL6R) OTCQL07Z IL6RA_HUMAN Decreases Expression [5]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Increases Cleavage [11]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Decreases Expression [5]
C-C motif chemokine 3 (CCL3) OTW2H3ND CCL3_HUMAN Decreases Expression [5]
Microtubule-associated protein tau (MAPT) OTMTP2Z7 TAU_HUMAN Decreases Expression [12]
C-C motif chemokine 4 (CCL4) OT6B8P25 CCL4_HUMAN Decreases Expression [5]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Decreases Expression [5]
C-C motif chemokine 5 (CCL5) OTSCA5CK CCL5_HUMAN Decreases Expression [5]
Matrix metalloproteinase-9 (MMP9) OTB2QDAV MMP9_HUMAN Decreases Expression [8]
Mitogen-activated protein kinase 3 (MAPK3) OTCYKGKO MK03_HUMAN Decreases Phosphorylation [8]
Mitogen-activated protein kinase 1 (MAPK1) OTH85PI5 MK01_HUMAN Decreases Phosphorylation [8]
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⏷ Show the Full List of 15 DOT(s)
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 [14]
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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 [15]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [16]
Monocarboxylate transporter 6 (SLC16A5) DT3I124 MOT6_HUMAN Substrate [17]
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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 [18]
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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 [19]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Decreases Activity [20]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Expression [21]
Taste receptor type 2 member 38 (TAS2R38) OTX5MM36 T2R38_HUMAN Decreases Activity [22]
Taste receptor type 2 member 43 (TAS2R43) OT70V8MZ T2R43_HUMAN Decreases Activity [22]
Solute carrier family 22 member 6 (SLC22A6) OTKRCBVM S22A6_HUMAN Decreases Activity [23]
Organic anion transporter 7 (SLC22A9) OTO4BJCC S22A9_HUMAN Decreases Activity [23]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [24]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [24]
Sodium-coupled monocarboxylate transporter 1 (SLC5A8) OTA0WELF SC5A8_HUMAN Decreases Activity [25]
Organic anion transporter 3 (SLC22A8) OT8BY933 S22A8_HUMAN Decreases Expression [26]
Solute carrier family 22 member 12 (SLC22A12) OT72ZAWS S22AC_HUMAN Affects Activity [27]
Solute carrier family 22 member 11 (SLC22A11) OTAJLNJZ S22AB_HUMAN Decreases Activity [28]
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⏷ Show the Full List of 13 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 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
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 Cell-based and cytokine-directed chemical screen to identify potential anti-multiple myeloma agents. Leuk Res. 2010 Jul;34(7):917-24. doi: 10.1016/j.leukres.2009.12.002. Epub 2010 Feb 8.
6 Potential role of drug transporters in the pathogenesis of medically intractable epilepsy. Epilepsia. 2005 Feb;46(2):224-35.
7 Metabolism of ipecac alkaloids cephaeline and emetine by human hepatic microsomal cytochrome P450s, and their inhibitory effects on P450 enzyme activities. Biol Pharm Bull. 2001 Jun;24(6):678-82.
8 Emetine inhibits migration and invasion of human non-small-cell lung cancer cells via regulation of ERK and p38 signaling pathways. Chem Biol Interact. 2015 Dec 5;242:25-33. doi: 10.1016/j.cbi.2015.08.014. Epub 2015 Aug 30.
9 Identification and Profiling of Environmental Chemicals That Inhibit the TGF/SMAD Signaling Pathway. Chem Res Toxicol. 2019 Dec 16;32(12):2433-2444. doi: 10.1021/acs.chemrestox.9b00228. Epub 2019 Nov 11.
10 IGF2BP1 induces neuroblastoma via a druggable feedforward loop with MYCN promoting 17q oncogene expression. Mol Cancer. 2023 May 29;22(1):88. doi: 10.1186/s12943-023-01792-0.
11 Apoptosis induces Bcl-XS and cleaved Bcl-XL in chronic lymphocytic leukaemia. Biochem Biophys Res Commun. 2011 Feb 18;405(3):480-5. doi: 10.1016/j.bbrc.2011.01.057. Epub 2011 Jan 20.
12 Pharmacologic reductions of total tau levels; implications for the role of microtubule dynamics in regulating tau expression. Mol Neurodegener. 2006 Jul 26;1:6. doi: 10.1186/1750-1326-1-6.
13 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.
14 Transport of organic anions across the basolateral membrane of proximal tubule cells. Rev Physiol Biochem Pharmacol. 2003;146:95-158.
15 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.
16 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.
17 Quercetin, Morin, Luteolin, and Phloretin Are Dietary Flavonoid Inhibitors of Monocarboxylate Transporter 6. Mol Pharm. 2017 Sep 5;14(9):2930-2936.
18 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.
19 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.
20 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.
21 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.
22 Probenecid inhibits the human bitter taste receptor TAS2R16 and suppresses bitter perception of salicin. PLoS One. 2011;6(5):e20123.
23 Inhibition of organic anion transporter (OAT) activity by cigarette smoke condensate. Toxicol In Vitro. 2017 Oct;44:27-35.
24 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.
25 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.
26 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.
27 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.
28 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.