Details of the Drug Combination

General Information of Drug Combination (ID: DC6H7OB)

Drug Combination Name
Pravastatin [3H]estrone-3-sulphate
Indication
Disease Entry Status REF
Hyperlipidaemia Phase 1 [1]
Component Drugs Pravastatin   DM6A0X7 [3H]estrone-3-sulphate   DMGPF0N
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Pravastatin
Disease Entry ICD 11 Status REF
Adult acute monocytic leukemia N.A. Approved [2]
Arteriosclerosis BD40 Approved [2]
Hypercholesterolaemia 5C80.0 Approved [3]
Hyperlipidemia, familial combined, LPL related N.A. Approved [2]
Hypertriglyceridemia 5C80.1 Approved [2]
Stroke 8B20 Investigative [2]
Pravastatin Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HMG-CoA reductase (HMGCR) TTPADOQ HMDH_HUMAN Inhibitor [5]
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Pravastatin Interacts with 11 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [6]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [7]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [8]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [9]
Bile salt export pump (ABCB11) DTJ0EW4 ABCBB_HUMAN Substrate [10]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [11]
Organic anion transporter 4 (SLC22A11) DT06JWZ S22AB_HUMAN Substrate [12]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [13]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Substrate [14]
Probable small intestine urate exporter (SLC17A4) DTHE530 S17A4_HUMAN Substrate [15]
Organic anion transporter 7 (SLC22A9) DTDI5S3 S22A9_HUMAN Substrate [16]
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⏷ Show the Full List of 11 DTP(s)
Pravastatin Interacts with 3 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [17]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Metabolism [18]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [19]
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Pravastatin Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Stromelysin-1 (MMP3) OTGBI74Z MMP3_HUMAN Increases ADR [20]
Liver carboxylesterase 1 (CES1) OT9L0LR8 EST1_HUMAN Increases ADR [20]
Kinesin-like protein KIF6 (KIF6) OTDH3MR4 KIF6_HUMAN Increases ADR [21]
Apolipoprotein E (APOE) OTFOWL2H APOE_HUMAN Increases ADR [20]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) OTRT3F3U HMDH_HUMAN Increases ADR [22]
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Indication(s) of [3H]estrone-3-sulphate
Disease Entry ICD 11 Status REF
Discovery agent N.A. Investigative [4]
[3H]estrone-3-sulphate Interacts with 6 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Sodium-independent organic anion transporter (SLCO1A2) TTUGD21 SO1A2_HUMAN Modulator [23]
Organic anion transporter B (SLCO2B1) TTDL3UZ SO2B1_HUMAN Modulator [24]
Organic anion transporter F (SLCO1C1) TT340CE SO1C1_HUMAN Modulator [25]
Liver organic anion transporter 1 (SLCO1B1) TTFGXEB SO1B1_HUMAN Modulator [26]
Organic anion transporter E (SLCO4A1) TTV1YIE SO4A1_HUMAN Modulator [27]
Organic anion transporter D (SLCO3A1) TT5CE6L SO3A1_HUMAN Modulator [28]
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⏷ Show the Full List of 6 DTT(s)
[3H]estrone-3-sulphate Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [29]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [30]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [31]
Tyrosine-protein phosphatase STS1/TULA2 (UBASH3B) DE10BJ5 UBS3B_HUMAN Metabolism [32]
Sulfatase (sulF) DE7WRSB A0A354WVI8_9BACT Metabolism [33]
Sulfatase (sulF) DE9THM7 A0A1F0P5Q0_9BACT Metabolism [34]
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⏷ Show the Full List of 6 DME(s)
[3H]estrone-3-sulphate Interacts with 20 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Interleukin-1 alpha (IL1A) OTPSGILV IL1A_HUMAN Decreases Expression [35]
Platelet-derived growth factor subunit A (PDGFA) OTCMZ0W8 PDGFA_HUMAN Decreases Expression [35]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Expression [35]
Solute carrier family 22 member 12 (SLC22A12) OT72ZAWS S22AC_HUMAN Increases Uptake [36]
Organic anion transporter 3 (SLC22A8) OT8BY933 S22A8_HUMAN Increases Import [37]
Solute carrier family 22 member 11 (SLC22A11) OTAJLNJZ S22AB_HUMAN Increases Import [38]
ABC-type organic anion transporter ABCA8 (ABCA8) OTCWLX6N ABCA8_HUMAN Affects Transport [39]
Solute carrier organic anion transporter family member 2B1 (SLCO2B1) OTERJ4VQ SO2B1_HUMAN Increases Import [40]
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Affects Export [41]
Solute carrier family 22 member 6 (SLC22A6) OTKRCBVM S22A6_HUMAN Increases Uptake [42]
Solute carrier family 22 member 7 (SLC22A7) OTKTNH1W S22A7_HUMAN Increases Uptake [43]
Sodium-dependent phosphate transport protein 4 (SLC17A3) OTMJWIBM NPT4_HUMAN Affects Transport [44]
Solute carrier organic anion transporter family member 1B1 (SLCO1B1) OTNEN8QK SO1B1_HUMAN Decreases Transport [45]
Organic anion transporter 7 (SLC22A9) OTO4BJCC S22A9_HUMAN Increases Import [37]
Solute carrier organic anion transporter family member 1A2 (SLCO1A2) OTO70C5O SO1A2_HUMAN Increases Import [46]
Solute carrier organic anion transporter family member 1B3 (SLCO1B3) OTOM3BUH SO1B3_HUMAN Increases Uptake [47]
Sodium-dependent organic anion transporter (SLC10A6) OTPMM183 SOAT_HUMAN Increases Response To Substance [48]
Dehydrogenase/reductase SDR family member 11 (DHRS11) OTU3J0ZL DHR11_HUMAN Increases Reduction [49]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Increases Export [50]
Steryl-sulfatase (STS) OTXTJQPC STS_HUMAN Decreases Sulfation [51]
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⏷ Show the Full List of 20 DOT(s)

References

1 Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors. Nat Rev Drug Discov. 2003 Jul;2(7):517-26.
2 Pravastatin 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: 2953).
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: 4748).
5 A randomized, double-blind trial comparing the efficacy and safety of pitavastatin versus pravastatin in patients with primary hypercholesterolemia. Atherosclerosis. 2002 Jun;162(2):373-9.
6 Role of transporters in the tissue-selective distribution and elimination of drugs: transporters in the liver, small intestine, brain and kidney. J Control Release. 2002 Jan 17;78(1-3):43-54.
7 Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
8 Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
9 The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B1*15. Pharmacogenet Genomics. 2008 May;18(5):424-33.
10 Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin. J Pharmacol Exp Ther. 2005 Aug;314(2):876-82.
11 Prediction of the overall renal tubular secretion and hepatic clearance of anionic drugs and a renal drug-drug interaction involving organic anion transporter 3 in humans by in vitro uptake experiments. Drug Metab Dispos. 2011 Jun;39(6):1031-8.
12 Inhibition of human organic anion transporter 3 mediated pravastatin transport by gemfibrozil and the metabolites in humans. Xenobiotica. 2007 Apr;37(4):416-26.
13 Relevance of conserved lysine and arginine residues in transmembrane helices for the transport activity of organic anion transporting polypeptide 1B3. Br J Pharmacol. 2010 Feb 1;159(3):698-708.
14 Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. J Pharmacol Exp Ther. 2004 Feb;308(2):438-45.
15 A Na+-phosphate cotransporter homologue (SLC17A4 protein) is an intestinal organic anion exporter. Am J Physiol Cell Physiol. 2012 Jun 1;302(11):C1652-60.
16 Variability in hepatic expression of organic anion transporter 7/SLC22A9, a novel pravastatin uptake transporter: impact of genetic and regulatory factors. Pharmacogenomics J. 2016 Aug;16(4):341-51.
17 Clinical pharmacokinetics of pravastatin: mechanisms of pharmacokinetic events. Clin Pharmacokinet. 2000 Dec;39(6):397-412.
18 Comparison of cytochrome P-450-dependent metabolism and drug interactions of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors lovastatin and pravastatin in the liver. Drug Metab Dispos. 1999 Feb;27(2):173-9.
19 In vitro comparative inhibition profiles of major human drug metabolising cytochrome P450 isozymes (CYP2C9, CYP2D6 and CYP3A4) by HMG-CoA reductase inhibitors. Eur J Clin Pharmacol. 1996;50(3):209-15.
20 ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
21 Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials: the CARE and WOSCOPS trials. J Am Coll Cardiol. 2008 Jan 29;51(4):435-43. doi: 10.1016/j.jacc.2007.05.057.
22 Pharmacogenetic study of statin therapy and cholesterol reduction. JAMA. 2004 Jun 16;291(23):2821-7. doi: 10.1001/jama.291.23.2821.
23 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. (Target id: 1219).
24 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. (Target id: 1224).
25 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. (Target id: 1222).
26 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. (Target id: 1220).
27 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. (Target id: 1226).
28 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. (Target id: 1225).
29 Estrogen regulation of the cytochrome P450 3A subfamily in humans. J Pharmacol Exp Ther. 2004 Nov;311(2):728-35.
30 Role of polymorphic human cytochrome P450 enzymes in estrone oxidation. Cancer Epidemiol Biomarkers Prev. 2006 Mar;15(3):551-8.
31 Pharmacogenomics of CYP2C9: functional and clinical considerations. J Pers Med. 2017 Dec 28;8(1).
32 Steroid sulfatase: a pivotal player in estrogen synthesis and metabolism. Mol Cell Endocrinol. 2011 Jul 4;340(2):154-60.
33 Parabacteroides pacaensis sp. nov. and Parabacteroides provencensis sp. nov., two new species identified from human gut microbiota. New Microbes New Infect. 2020 Jan 7;34:100642.
34 Two rheumatoid arthritis-specific autoantigens correlate microbial immunity with autoimmune responses in joints. J Clin Invest. 2017 Aug 1;127(8):2946-2956.
35 Atheroprotective effect of estriol and estrone sulfate on human vascular smooth muscle cells. J Steroid Biochem Mol Biol. 2000 Jan-Feb;72(1-2):71-8. doi: 10.1016/s0960-0760(99)00149-1.
36 Lack of interaction of the fluorosurfactant C6O4 with human renal transporters: In vitro/in silico analysis. Toxicology. 2022 Jun 30;476:153257. doi: 10.1016/j.tox.2022.153257. Epub 2022 Jul 12.
37 Inhibition of organic anion transporter (OAT) activity by cigarette smoke condensate. Toxicol In Vitro. 2017 Oct;44:27-35.
38 Characterization of cellular uptake of perfluorooctanoate via organic anion-transporting polypeptide 1A2, organic anion transporter 4, and urate transporter 1 for their potential roles in mediating human renal reabsorption of perfluorocarboxylates. Toxicol Sci. 2010 Oct;117(2):294-302. doi: 10.1093/toxsci/kfq219. Epub 2010 Jul 16.
39 Functional analysis of ABCA8, a new drug transporter. Biochem Biophys Res Commun. 2002 Oct 18;298(1):41-5.
40 Predominant contribution of organic anion transporting polypeptide OATP-B (OATP2B1) to apical uptake of estrone-3-sulfate by human intestinal Caco-2 cells. Drug Metab Dispos. 2006 Aug;34(8):1423-31.
41 Directional trans-epithelial transport of organic anions in porcine LLC-PK1 cells that co-express human OATP1B1 (OATP-C) and MRP2. Biochem Pharmacol. 2005 Feb 1;69(3):415-23.
42 Human organic anion transporter hOAT3 is a potent transporter of cephalosporin antibiotics, in comparison with hOAT1. Biochem Pharmacol. 2005 Oct 1;70(7):1104-13.
43 Transport mechanism and substrate specificity of human organic anion transporter 2 (hOat2 [SLC22A7]). J Pharm Pharmacol. 2005 May;57(5):573-8.
44 Functional analysis of human sodium-phosphate transporter 4 (NPT4/SLC17A3) polymorphisms. J Pharmacol Sci. 2011;115(2):249-53. doi: 10.1254/jphs.10228sc. Epub 2011 Jan 26.
45 Functional analysis of a mutation in the SLCO1B1 gene (c.1628T>G) identified in a Japanese patient with pravastatin-induced myopathy. Pharmacogenomics J. 2009 Jun;9(3):185-93. doi: 10.1038/tpj.2009.3. Epub 2009 Feb 24.
46 Interaction of methotrexate with organic-anion transporting polypeptide 1A2 and its genetic variants. J Pharmacol Exp Ther. 2006 Aug;318(2):521-9.
47 Identification of the organic anion transporting polypeptides responsible for the hepatic uptake of the major metabolite of epyrifenacil, S-3100-CA, in mice. Pharmacol Res Perspect. 2021 Oct;9(5):e00877. doi: 10.1002/prp2.877.
48 Estrone-3-Sulfate Stimulates the Proliferation of T47D Breast Cancer Cells Stably Transfected With the Sodium-Dependent Organic Anion Transporter SOAT (SLC10A6). Front Pharmacol. 2018 Aug 21;9:941. doi: 10.3389/fphar.2018.00941. eCollection 2018.
49 Rabbit dehydrogenase/reductase SDR family member 11 (DHRS11): Its identity with acetohexamide reductase with broad substrate specificity and inhibitor sensitivity, different from human DHRS11. Chem Biol Interact. 2019 May 25;305:12-20. doi: 10.1016/j.cbi.2019.03.026. Epub 2019 Mar 26.
50 Uremic toxins inhibit transport by breast cancer resistance protein and multidrug resistance protein 4 at clinically relevant concentrations. PLoS One. 2011 Apr 4;6(4):e18438. doi: 10.1371/journal.pone.0018438.
51 Stilbene-based inhibitors of estrone sulfatase with a dual mode of action in human breast cancer cells. Arch Pharm (Weinheim). 2004 Dec;337(12):634-44. doi: 10.1002/ardp.200400904.