General Information of Drug Combination (ID: DC5YOFB)

Drug Combination Name
Ginsenoside Rb1 Probenecid
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Ginsenoside Rb1   DMF70AB Probenecid   DMMFWOJ
N.A. 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: 5.58
Bliss Independence Score: 5.58
Loewe Additivity Score: 18.98
LHighest Single Agent (HSA) Score: 18.98

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Ginsenoside Rb1 Interacts with 23 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Beta-glucosidase (bglA) DEUO7V8 A0A509DD13_9STRE Metabolism [4]
Beta-glucosidase (bglA) DE4LKZ9 A0A3D1ZWL4_9BIFI Metabolism [4]
Beta-glucosidase (bglA) DEM6GYO A0A351PC96_9FIRM Metabolism [5], [4]
Beta-glucosidase (bglA) DE9N4OU C6WCL5_ACTMD Metabolism [6]
Beta-glucosidase (bglA) DERPJZ6 A0A4Q4LS82_BIFAN Metabolism [7]
Beta-glucosidase (bglA) DEVLXCG R7LVY8_9FUSO Metabolism [4]
Beta-glucosidase (bglA) DEUQTKA A0A249DCH3_LACRH Metabolism [7]
Beta-glucosidase (bglA) DEXRUS1 A0A267WL33_9BIFI Metabolism [8]
Beta-glucosidase (bglA) DERX7ML A0A3B8TKP6_9FIRM Metabolism [8]
Beta-glucosidase (bglA) DEOHI3U A0A0P0FEZ9_BACT4 Metabolism [8]
Beta-glucosidase (bglA) DE46IH1 A0A1T4QCU7_9PROT Metabolism [9]
Beta-glucosidase (bglA) DEE8WXK A0A076JJU4_BIFAD Metabolism [8]
Beta-glucosidase (bglA) DECBSVP A0A126SWK8_9BIFI Metabolism [8]
Beta-glucosidase (bglA) DEAVLU4 BGLFU_BIFBR Metabolism [8]
Beta-glucosidase (bglA) DEPBQES BGLS_BUTFI Metabolism [8]
Beta-glucosidase (bglA) DEGVUWH A0A174JG46_9FIRM Metabolism [8]
Beta-glucosidase (bglA) DEE8RS0 A0A174GPV4_9FIRM Metabolism [8]
Beta-glucosidase (bglA) DEC0M8H A0A174ZK85_9FIRM Metabolism [8]
Beta-glucosidase (bglA) DE2OMS0 A0A173UNF6_9FIRM Metabolism [8]
Beta-glucosidase (bglA) DEPUNVR A0A395V8H8_9FIRM Metabolism [8]
Beta-glucosidase (bglA) DEX7SAW A0A3R6A2W5_9FIRM Metabolism [8]
Beta-glucosidase (bglA) DEE3I1P A0A412BAD0_9FIRM Metabolism [8]
Beta-glucosidase (bglA) DEASJG5 A5ZMW4_9FIRM Metabolism [8]
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⏷ Show the Full List of 23 DME(s)
Ginsenoside Rb1 Interacts with 7 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Progesterone receptor (PGR) OT0FZ3QE PRGR_HUMAN Increases Expression [10]
Heme oxygenase 1 (HMOX1) OTC1W6UX HMOX1_HUMAN Increases Expression [11]
Potassium voltage-gated channel subfamily E member 1 (KCNE1) OTZNQUW9 KCNE1_HUMAN Increases Expression [12]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Increases Phosphorylation [11]
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Affects Activity [13]
Sequestosome-1 (SQSTM1) OTGY5D5J SQSTM_HUMAN Decreases Expression [14]
Nuclear factor erythroid 2-related factor 2 (NFE2L2) OT0HENJ5 NF2L2_HUMAN Increases Expression [15]
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⏷ Show the Full List of 7 DOT(s)
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 [17]
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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 [18]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [19]
Monocarboxylate transporter 6 (SLC16A5) DT3I124 MOT6_HUMAN Substrate [20]
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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 [21]
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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 [22]
Multidrug resistance-associated protein 1 (ABCC1) OTGUN89S MRP1_HUMAN Decreases Activity [23]
Cytochrome P450 3A4 (CYP3A4) OTQGYY83 CP3A4_HUMAN Decreases Expression [24]
Taste receptor type 2 member 38 (TAS2R38) OTX5MM36 T2R38_HUMAN Decreases Activity [25]
Taste receptor type 2 member 43 (TAS2R43) OT70V8MZ T2R43_HUMAN Decreases Activity [25]
Solute carrier family 22 member 6 (SLC22A6) OTKRCBVM S22A6_HUMAN Decreases Activity [26]
Organic anion transporter 7 (SLC22A9) OTO4BJCC S22A9_HUMAN Decreases Activity [26]
Interleukin-8 (CXCL8) OTS7T5VH IL8_HUMAN Increases Expression [27]
C-C motif chemokine 2 (CCL2) OTAD2HEL CCL2_HUMAN Increases Expression [27]
Sodium-coupled monocarboxylate transporter 1 (SLC5A8) OTA0WELF SC5A8_HUMAN Decreases Activity [28]
Organic anion transporter 3 (SLC22A8) OT8BY933 S22A8_HUMAN Decreases Expression [29]
Solute carrier family 22 member 12 (SLC22A12) OT72ZAWS S22AC_HUMAN Affects Activity [30]
Solute carrier family 22 member 11 (SLC22A11) OTAJLNJZ S22AB_HUMAN Decreases Activity [31]
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⏷ Show the Full List of 13 DOT(s)

References

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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 Constitutive beta-glucosidases hydrolyzing ginsenoside Rb1 and Rb2 from human intestinal bacteria. Biol Pharm Bull. 2000 Dec;23(12):1481-5.
5 Intestinal bacterial hydrolysis is required for the appearance of compound K in rat plasma after oral administration of ginsenoside Rb1 from Panax ginseng. J Pharm Pharmacol. 1998 Oct;50(10):1155-60.
6 Characterization of the ginsenoside-transforming recombinant beta-glucosidase from Actinosynnema mirum and bioconversion of major ginsenosides into minor ginsenosides. Appl Microbiol Biotechnol. 2013 Jan;97(2):649-59.
7 Fermentation of protopanaxadiol type ginsenosides (PD) with probiotic Bifidobacterium lactis and Lactobacillus rhamnosus. Appl Microbiol Biotechnol. 2017 Jul;101(13):5427-5437.
8 Developing a metagenomic view of xenobiotic metabolism. Pharmacol Res. 2013 Mar;69(1):21-31.
9 Genus Enhydrobacter Staley et al. 1987 should be recognized as a member of the family Rhodospirillaceae within the class Alphaproteobacteria. Microbiol Immunol. 2012 Jan;56(1):21-6.
10 Metabolism of ginsenoside Re by human intestinal microflora and its estrogenic effect. Biol Pharm Bull. 2005 Oct;28(10):1903-8. doi: 10.1248/bpb.28.1903.
11 Ginsenoside Rb1 protects against 6-hydroxydopamine-induced oxidative stress by increasing heme oxygenase-1 expression through an estrogen receptor-related PI3K/Akt/Nrf2-dependent pathway in human dopaminergic cells. Toxicol Appl Pharmacol. 2010 Jan 1;242(1):18-28. doi: 10.1016/j.taap.2009.09.009. Epub 2009 Sep 23.
12 Ginsenosides may enhance the functionality of human embryonic stem cell-derived cardiomyocytes in vitro. Reprod Sci. 2014 Oct;21(10):1312-8. doi: 10.1177/1933719114525269. Epub 2014 Mar 10.
13 Modulating effect of ginseng saponins on heterologously expressed HERG currents in Xenopus oocytes. Acta Pharmacol Sin. 2005 May;26(5):551-8. doi: 10.1111/j.1745-7254.2005.00116.x.
14 Ginsenoside Rb1 alleviates liver injury induced by 3-chloro-1,2-propanediol by stimulating autophagic flux. J Food Sci. 2021 Dec;86(12):5503-5515. doi: 10.1111/1750-3841.15968. Epub 2021 Nov 23.
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16 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.
17 Transport of organic anions across the basolateral membrane of proximal tubule cells. Rev Physiol Biochem Pharmacol. 2003;146:95-158.
18 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.
19 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.
20 Quercetin, Morin, Luteolin, and Phloretin Are Dietary Flavonoid Inhibitors of Monocarboxylate Transporter 6. Mol Pharm. 2017 Sep 5;14(9):2930-2936.
21 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.
22 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.
23 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.
24 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.
25 Probenecid inhibits the human bitter taste receptor TAS2R16 and suppresses bitter perception of salicin. PLoS One. 2011;6(5):e20123.
26 Inhibition of organic anion transporter (OAT) activity by cigarette smoke condensate. Toxicol In Vitro. 2017 Oct;44:27-35.
27 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.
28 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.
29 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.
30 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.
31 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.