TENIVASTATIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H40O6
Molecular Weight	436.5815
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CCC(C)(C)C(=O)O[C@H]1C[C@@H](C)C=C2C=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@@H]12

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	436.5815
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	7 / 7
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Simvastatin is a HMG-CoA Reductase Inhibitor that is FDA approved for the treatment of hypercholesterolemia and for the reduction in the risk of cardiac heart disease mortality and cardiovascular events. It reduces levels of "bad" cholesterol (low-density lipoprotein, or LDL) and triglycerides in the blood, while increasing levels of "good" cholesterol (high-density lipoprotein, or HDL). Common adverse reactions include abdominal pain, constipation, nausea, headache, upper respiratory infection. Cases of myopathy/rhabdomyolysis have been observed with simvastatin co-administered with lipid-modifying doses ( ≥ 1 g/day niacin) of niacin-containing products. The risk of myopathy, including rhabdomyolysis, is increased by concomitant administration of amiodarone, dronedarone, ranolazine, or calcium channel blockers such as verapamil, diltiazem, or amlodipine.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Solute carrier organic anion transporter family member 3A1 6	Binding Agent 1,076
Solute carrier organic anion transporter family member 1B1 32	Binding Agent 1,076
3-hydroxy-3-methylglutaryl-coenzyme A reductase 9	Inhibitor 8,504
Cytochrome P450 3A4 127	Substrate 661
HMG-CoA reductase 49	Inhibitor 8,504	4.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Unknown 2,596
Coronary heart disease mortality and cardiovascular events 6	Preventing	Approved 8,583	ZOCOR
Hyperlipidemia 82	Primary	Approved 8,583	ZOCOR
Homozygous and heterozygous familial hypercholesterolemia 6	Primary	Approved 8,583	ZOCOR

C_max

Value	Dose	Analyte	Population
6.85 ng/mL	40 mg single, oral	SIMVASTATIN plasma	Homo sapiens
1.93 ng/mL	40 mg single, oral	TENIVASTATIN plasma	Homo sapiens
5.006 ng/mL	20 mg single, oral	SIMVASTATIN plasma	Homo sapiens
54.711 ng/mL	80 mg single, oral	SIMVASTATIN plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
38.142 ng*h/mL	20 mg single, oral	SIMVASTATIN plasma	Homo sapiens
34.351 ng*h/mL	20 mg single, oral	SIMVASTATIN plasma	Homo sapiens
235.795 ng × h/mL	80 mg single, oral	SIMVASTATIN plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.87 h	80 mg single, oral		SIMVASTATIN plasma	Homo sapiens

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,946 inhibitor 2,252	substrate 1,193 inhibitor 2,438	substrate 1,388 inhibitor 2,507	inhibitor 2,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BSEP 550 CYP2C8 1,057 CYP2C19 2,057 P-gp 1,741	CYP3A5 446 CYP2A6 626 CYP2C8 810 CYP2C19 1,119 CYP1A2 1,197 CYP2E1 729 OATP2 11 OATP1B1 503 OATP1B3 435

Drug as perpetrator

Show entries

Target	Modality	Activity
CYP3A4 2,633	inhibitor 4,027	moderate [Ki 10 uM]
CYP2C8 1,117	inhibitor 4,027	moderate [Ki 7.1 uM]
CYP2C9 2,497	inhibitor 4,027	moderate
CYP2D6 2,546	inhibitor 4,027	moderate
CYP2C19 2,141	inhibitor 4,027	no

Showing 1 to 5 of 7 entries

Previous1 2Next

Drug as victim

Show entries

Target	Modality	Activity	Clinical evidence
CYP3A4 1,946	substrate 4,014	major	yes (co-administration study)
CYP3A5 446	substrate 4,014	minor
CYP1A2 1,197	substrate 4,014	no
CYP2A6 626	substrate 4,014	no
CYP2C19 1,119	substrate 4,014	no

Showing 1 to 5 of 12 entries

Previous1 2 3Next

Tox targets

Show entries

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2,263	inhibitor 2,237

Showing 1 to 1 of 1 entries

Previous1Next

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9150	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9150
eMolecules	11021557	https://www.emolecules.com/cgi-bin/more?vid=11021557
eMolecules	2724261	https://www.emolecules.com/cgi-bin/more?vid=2724261
eMolecules	36754543	https://www.emolecules.com/cgi-bin/more?vid=36754543
MolPort	MolPort-002-507-345	https://www.molport.com/shop/molecule-link/MolPort-002-507-345

Showing 1 to 5 of 7 entries

Previous1 2Next

PubMed

Show entries

Title	Date	PubMed
Advantages of lipid-lowering therapy in cerebral ischemia: role of HMG-CoA reductase inhibitors.	2001	11244205
Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice.	2001 Apr	11283400
A new simvastatin (mevinolin)-resistance marker from Haloarcula hispanica and a new Haloferax volcanii strain cured of plasmid pHV2.	2001 Apr	11283291
Rhabdomyolysis due to simvastatin in a transplant patient: Are some statins safer than others?	2001 Apr	11274299
Comparative study of HMG-CoA reductase inhibitors on fibrinogen.	2001 Apr	11254918

Showing 1 to 5 of 50 entries

Previous1 2 3 4 5…10Next

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

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
Record UNII	9L6M5TH46B
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

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)-

Preferred Name

English

TENIVASTATIN

Official Name

English

SIMVASTATIN ACID

Common Name

English

tenivastatin [INN]

Common Name

English

SIMVASTATIN IMPURITY A [EP IMPURITY]