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Details

Stereochemistry ABSOLUTE
Molecular Formula C25H40O6
Molecular Weight 436.5825
Optical Activity UNSPECIFIED
Defined Stereocenters 7 / 7
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TENIVASTATIN

SMILES

CCC(C)(C)C(=O)O[C@@]1([H])C[C@@]([H])(C)C=C2C=C[C@]([H])(C)[C@]([H])(CC[C@]([H])(C[C@]([H])(CC(=O)O)O)O)[C@]21[H]

InChI

InChIKey=XWLXKKNPFMNSFA-HGQWONQESA-N
InChI=1S/C25H40O6/c1-6-25(4,5)24(30)31-21-12-15(2)11-17-8-7-16(3)20(23(17)21)10-9-18(26)13-19(27)14-22(28)29/h7-8,11,15-16,18-21,23,26-27H,6,9-10,12-14H2,1-5H3,(H,28,29)/t15-,16-,18+,19+,20-,21-,23-/m0/s1

HIDE SMILES / InChI

Molecular Formula C25H40O6
Molecular Weight 436.5825
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 7 / 7
E/Z Centers 0
Optical Activity UNSPECIFIED

Tenivastatin (well known as simvastatin acid or simvastatin hydroxy acid) is a pharmacologically active metabolite, which is formed in the mammalian organism from lactone prodrug, simvastatin. Tenivastatin is a potent reversible inhibitor of HMGCR (HMG-CoA reductase), reduces cholesterol synthesis and increases low-density lipoprotein (LDL) receptors on cell membranes of liver and extrahepatic tissues. It is also a substrate of organic anion transporting polypeptide 1B1 (OATP1B1/Oatp2), an influx transporter expressed on the sinusoidal membrane of hepatocytes. Recent studies have shown that OATP1B1 plays a clinically important role in the hepatic elimination of several drugs including statins, via mediating the hepatic uptake. In addition, was discovered, that the tenivastatin was a substrate of another transporter protein, human organic anion transporting polypeptide 3A1 (OATP3A1), which is predominately expressed in the heart. Presence of OATP3A1 in cardiomyocytes suggested that transporter could modulate the exposure of cardiac tissue to simvastatin acid due to its enrichment in cardiomyocytes. Increases in the uptake of simvastatin acid by OATP3A1 when combined with OATP substrates suggest the potential for drug-drug interactions that could influence clinical outcomes.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Q9UIG8
Gene ID: 28232
Gene Symbol: SLCO3A1
Target Organism: Homo sapiens (Human)
Target ID: Q9Y6L6
Gene ID: 10599
Gene Symbol: SLCO1B1
Target Organism: Homo sapiens (Human)
Target ID: P04035
Gene ID: 3156
Gene Symbol: HMGCR
Target Organism: Homo sapiens (Human)
PubMed

PubMed

TitleDatePubMed
The influences of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of simvastatin, in relation to CYP3A4 inhibition.
2017 Apr

Sample Use Guides

The pleiotropic effects and uptake of simvastatin acid were analyzed in primary human cardiomyocytes and HEK293 cells transfected with the OATP3A1 (Human organic anion transporting polypeptide 3A1) gene. It was observed a pH-dependent effect on OATP3A1 uptake, with more efficient simvastatin acid uptake at pH5.5 in HEK293 cells transfected with the OATP3A1 gene. The Michaelis-Menten constant (Km) for simvastatin acid uptake by OATP3A1 was 0.017±0.002μM and the Vmax was 0.995±0.027fmol/min/105 cells. Uptake of simvastatin acid was significantly increased by known (benzylpenicillin and estrone-3-sulfate) and potential (indoxyl sulfate and cyclosporine) substrates of OATP3A1.
Substance Class Chemical
Created
by admin
on Fri Jun 25 23:50:57 UTC 2021
Edited
by admin
on Fri Jun 25 23:50:57 UTC 2021
Record UNII
9L6M5TH46B
Record Status Validated (UNII)
Record Version
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Name Type Language
TENIVASTATIN
INN   WHO-DD  
INN  
Official Name English
SIMVASTATIN ACID
Common Name English
SIMVASTATIN SPECIFIED IMPURITY A [EP]
Common Name English
TENIVASTATIN [INN]
Common Name English
1-NAPHTHALENEHEPTANOIC ACID, 8-(2,2-DIMETHYL-1-OXOBUTOXY)-1,2,6,7,8,8A-HEXAHYDRO-.BETA.,.DELTA.-DIHYDROXY-2,6-DIMETHYL-, (.BETA.R,.DELTA.R,1S,2S,6R,8S,8AR)-
Common Name English
TENIVASTATIN [WHO-DD]
Common Name English
SIMVASTATIN IMPURITY, SIMVASTATIN HYDROXYACID- [USP]
Common Name English
SIMVASTATIN HYDROXY ACID
Common Name English
SIMVASTATIN CARBOXYLIC ACID
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1655
Created by admin on Fri Jun 25 23:50:57 UTC 2021 , Edited by admin on Fri Jun 25 23:50:57 UTC 2021
Code System Code Type Description
DRUG BANK
DB14714
Created by admin on Fri Jun 25 23:50:57 UTC 2021 , Edited by admin on Fri Jun 25 23:50:57 UTC 2021
PRIMARY
PUBCHEM
64718
Created by admin on Fri Jun 25 23:50:57 UTC 2021 , Edited by admin on Fri Jun 25 23:50:57 UTC 2021
PRIMARY
INN
8120
Created by admin on Fri Jun 25 23:50:57 UTC 2021 , Edited by admin on Fri Jun 25 23:50:57 UTC 2021
PRIMARY
FDA UNII
9L6M5TH46B
Created by admin on Fri Jun 25 23:50:57 UTC 2021 , Edited by admin on Fri Jun 25 23:50:57 UTC 2021
PRIMARY
MESH
C063287
Created by admin on Fri Jun 25 23:50:57 UTC 2021 , Edited by admin on Fri Jun 25 23:50:57 UTC 2021
PRIMARY
NCI_THESAURUS
C96309
Created by admin on Fri Jun 25 23:50:57 UTC 2021 , Edited by admin on Fri Jun 25 23:50:57 UTC 2021
PRIMARY
CAS
121009-77-6
Created by admin on Fri Jun 25 23:50:57 UTC 2021 , Edited by admin on Fri Jun 25 23:50:57 UTC 2021
PRIMARY
ChEMBL
CHEMBL1201391
Created by admin on Fri Jun 25 23:50:57 UTC 2021 , Edited by admin on Fri Jun 25 23:50:57 UTC 2021
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
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PRODRUG -> METABOLITE ACTIVE
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PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
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ACTIVE MOIETY