General Information of Drug Combination (ID: DCOYTTQ)

Drug Combination Name
Triflupromazine Probenecid
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Triflupromazine   DMKFQJP 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: 17.75
Bliss Independence Score: 17.75
Loewe Additivity Score: 32.69
LHighest Single Agent (HSA) Score: 32.69

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Triflupromazine
Disease Entry ICD 11 Status REF
Nausea MD90 Approved [2]
Psychotic disorder 6A20-6A25 Approved [3]
Vomiting MD90 Approved [2]
Schizophrenia 6A20 Withdrawn from market [4]
Middle East Respiratory Syndrome (MERS) 1D64 Investigative [5]
Severe acute respiratory syndrome (SARS) 1D65 Investigative [5]
Triflupromazine Interacts with 2 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HUMAN clathrin-mediated endocytosis (RME) TTAIY2U N.A. Inhibitor [5]
5-HT 2B receptor (HTR2B) TT0K1SC 5HT2B_HUMAN Antagonist [8]
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Triflupromazine Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [9]
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Triflupromazine Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [10]
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Indication(s) of Probenecid
Disease Entry ICD 11 Status REF
Acute gonococcal cervicitis N.A. Approved [6]
Gout FA25 Approved [7]
Hyperuricaemia 5C55.Y Approved [7]
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 [12]
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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 [13]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [14]
Monocarboxylate transporter 6 (SLC16A5) DT3I124 MOT6_HUMAN Substrate [15]
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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 [16]
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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 [17]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Decreases Activity [18]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Expression [19]
Taste receptor type 2 member 38 (TAS2R38) OTX5MM36 T2R38_HUMAN Decreases Activity [20]
Taste receptor type 2 member 43 (TAS2R43) OT70V8MZ T2R43_HUMAN Decreases Activity [20]
Solute carrier family 22 member 6 (SLC22A6) OTKRCBVM S22A6_HUMAN Decreases Activity [21]
Organic anion transporter 7 (SLC22A9) OTO4BJCC S22A9_HUMAN Decreases Activity [21]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [22]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [22]
Sodium-coupled monocarboxylate transporter 1 (SLC5A8) OTA0WELF SC5A8_HUMAN Decreases Activity [23]
Organic anion transporter 3 (SLC22A8) OT8BY933 S22A8_HUMAN Decreases Expression [24]
Solute carrier family 22 member 12 (SLC22A12) OT72ZAWS S22AC_HUMAN Affects Activity [25]
Solute carrier family 22 member 11 (SLC22A11) OTAJLNJZ S22AB_HUMAN Decreases Activity [26]
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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 Triflupromazine 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: 4330).
4 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
5 Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob Agents Chemother. 2014 Aug;58(8):4885-93.
6 Probenecid FDA Label
7 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).
8 Some properties of 5-hydroxytryptamine receptors in the hindquarters of the rat. Br J Pharmacol. 1979 Sep;67(1):79-85.
9 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
10 Why are most phospholipidosis inducers also hERG blockers?. Arch Toxicol. 2017 Dec;91(12):3885-3895. doi: 10.1007/s00204-017-1995-9. Epub 2017 May 27.
11 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.
12 Transport of organic anions across the basolateral membrane of proximal tubule cells. Rev Physiol Biochem Pharmacol. 2003;146:95-158.
13 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.
14 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.
15 Quercetin, Morin, Luteolin, and Phloretin Are Dietary Flavonoid Inhibitors of Monocarboxylate Transporter 6. Mol Pharm. 2017 Sep 5;14(9):2930-2936.
16 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.
17 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.
18 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.
19 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.
20 Probenecid inhibits the human bitter taste receptor TAS2R16 and suppresses bitter perception of salicin. PLoS One. 2011;6(5):e20123.
21 Inhibition of organic anion transporter (OAT) activity by cigarette smoke condensate. Toxicol In Vitro. 2017 Oct;44:27-35.
22 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.
23 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.
24 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.
25 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.
26 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.