Details of the Drug-Related molecule(s) Expression Atlas

General Information of Drug (ID: DM6A0X7)

Drug Name
Pravastatin Drug Info
Synonyms
Eptastatin; Oliprevin; Pravastatina; Pravastatine; Pravastatinum; Pravator; Vasten; Pravastatin Sodium Salt; Pravastatina [Spanish]; Pravastatine [French]; Pravastatinum [Latin]; KS-5015; Pravachol (TN); Pravastatin (INN); Pravastatin [INN:BAN]; Pravastatin tert-Octylamine Salt; Pravator (TN); RMS-431; Selektine (TN); SQ-31,000; (3R,5R)-3,5-dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-{[(2S)-2-methylbutanoyl]oxy}-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]heptanoic acid; (3R,5R)-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-[(2S)-2-methylbutanoyl]oxy-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid; 1,2,6,7,8,8a-hexahydro-beta,delta,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-, (1S-(1alpha(betaS*,deltaS*),2alpha,6alpha,8beta(R*),8aalpha))-1-Naphthaleneheptanoic acid
Indication
Disease Entry ICD 11 Status REF
Adult acute monocytic leukemia Approved [1]
Arteriosclerosis BD40 Approved [1]
Hypercholesterolaemia 5C80.0 Approved [2]
Hyperlipidemia, familial combined, LPL related Approved [1]
Hypertriglyceridemia 5C80.1 Approved [1]
Stroke 8B20 Investigative [1]
Therapeutic Class
Anticholesteremic Agents
Cross-matching ID
PubChem CID
54687
ChEBI ID
CHEBI:63618
CAS Number
CAS 81093-37-0
TTD Drug ID
DM6A0X7
VARIDT Drug ID
DR00045
INTEDE Drug ID
DR1327
ACDINA Drug ID
D00548

Molecule(s) Related to This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
HMG-CoA reductase (HMGCR) TTPADOQ HMDH_HUMAN Inhibitor [3]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID Highest Status REF
Probable small intestine urate exporter (SLC17A4) DTHE530 S17A4_HUMAN Approved [4]
Organic anion transporter 7 (SLC22A9) DTDI5S3 S22A9_HUMAN Approved [5]
Bile salt export pump (ABCB11) DTJ0EW4 ABCBB_HUMAN Approved [6]
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Approved [7]
Organic anion transporter 4 (SLC22A11) DT06JWZ S22AB_HUMAN Approved [8]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Approved [9]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Approved [10]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Approved [11]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Approved [12]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Approved [13]
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Approved [14]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID Highest Status REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Approved [15]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Approved [16]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Approved [17]

The Expression Level of Molecule(s) in Normal Tissue of Major ADME-Related Organs

Molecule Molecule Type Gene Name Liver Colon Kidney Small Intestine
HMG-CoA reductase (HMGCR) DTT HMGCR 6.357 6.256 5.17 6.85
Organic anion transporter 3 (SLC22A8) DTP OAT3 2.722 2.07 8.103 3.597
P-glycoprotein 1 (ABCB1) DTP P-GP 7.009 6.988 7.442 8.135
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTP OATP2B1 8.165 6.597 6.591 6.397
Bile salt export pump (ABCB11) DTP BSEP 6.055 5.066 4.456 4.797
Breast cancer resistance protein (ABCG2) DTP BCRP 6.732 7.513 6.326 9.277
Probable small intestine urate exporter (SLC17A4) DTP SLC17A4 6.717 7.107 6.747 7.338
Multidrug resistance-associated protein 2 (ABCC2) DTP MRP2 7.751 4.17 6.425 6.282
Organic anion transporting polypeptide 1B3 (SLCO1B3) DTP OATP1B3 8.873 2.17 2.485 3.322
Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP OATP1B1 9.79 0.485 3.511 2.07
Organic anion transporter 4 (SLC22A11) DTP OAT4 1.926 2.585 6.595 3.336
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 10.08 7.207 5.403 9.211
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 11.76 5.931 6.164 9.423
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 11.692 6.58 4.984 9.089
Molecule Expression Atlas in Normal Tissue of Major ADME-related organs

The Expression Level of Molecule(s) between Disease Section and Healthy Individual Tissue

The Studied Disease Adult acute monocytic leukemia
ICD Disease Classification
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
HMG-CoA reductase (HMGCR) DTT HMGCR 1.01E-05 0.65 1.53
Organic anion transporter 3 (SLC22A8) DTP OAT3 1.54E-03 -5.09E-01 -1.49E+00
P-glycoprotein 1 (ABCB1) DTP P-GP 3.29E-14 -7.08E-01 -1.99E+00
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTP OATP2B1 3.80E-01 -1.23E-02 -5.33E-02
Bile salt export pump (ABCB11) DTP BSEP 2.41E-01 -3.08E-02 -2.35E-01
Breast cancer resistance protein (ABCG2) DTP BCRP 2.28E-08 -3.66E-01 -8.07E-01
Probable small intestine urate exporter (SLC17A4) DTP SLC17A4 1.00E-02 -1.74E-01 -8.13E-01
Multidrug resistance-associated protein 2 (ABCC2) DTP MRP2 4.30E-02 -2.29E-01 -9.10E-01
Organic anion transporter 7 (SLC22A9) DTP OAT7 1.92E-04 -4.34E-01 -1.40E+00
Organic anion transporting polypeptide 1B3 (SLCO1B3) DTP OATP1B3 1.65E-01 -6.07E-02 -3.77E-01
Organic anion transporting polypeptide 1B1 (SLCO1B1) DTP OATP1B1 3.27E-01 -5.78E-02 -3.84E-01
Organic anion transporter 4 (SLC22A11) DTP OAT4 3.76E-03 -3.49E-01 -8.70E-01
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 3.65E-02 -8.90E-02 -5.58E-01
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 2.63E-03 -1.18E-01 -3.80E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 3.24E-05 -3.48E-01 -1.34E+00
Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

References

1 Pravastatin FDA Label
2 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).
3 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.
4 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.
5 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.
6 Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin. J Pharmacol Exp Ther. 2005 Aug;314(2):876-82.
7 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.
8 Inhibition of human organic anion transporter 3 mediated pravastatin transport by gemfibrozil and the metabolites in humans. Xenobiotica. 2007 Apr;37(4):416-26.
9 Functional characterization of pH-sensitive organic anion transporting polypeptide OATP-B in human. J Pharmacol Exp Ther. 2004 Feb;308(2):438-45.
10 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.
11 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.
12 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.
13 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.
14 Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
15 Clinical pharmacokinetics of pravastatin: mechanisms of pharmacokinetic events. Clin Pharmacokinet. 2000 Dec;39(6):397-412.
16 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.
17 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.