U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula 2C25H23FNO4.Mg
Molecular Weight 865.2106
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 2
Charge 0

SHOW SMILES / InChI
Structure of PITAVASTATIN MAGNESIUM

SMILES

[Mg++].O[C@H](C[C@H](O)\C=C\C1=C(C2=CC=C(F)C=C2)C3=CC=CC=C3N=C1C4CC4)CC([O-])=O.O[C@H](C[C@H](O)\C=C\C5=C(C6=CC=C(F)C=C6)C7=CC=CC=C7N=C5C8CC8)CC([O-])=O

InChI

InChIKey=MPAZKXHCZWDZDY-FFNUKLMVSA-L
InChI=1S/2C25H24FNO4.Mg/c2*26-17-9-7-15(8-10-17)24-20-3-1-2-4-22(20)27-25(16-5-6-16)21(24)12-11-18(28)13-19(29)14-23(30)31;/h2*1-4,7-12,16,18-19,28-29H,5-6,13-14H2,(H,30,31);/q;;+2/p-2/b2*12-11+;/t2*18-,19-;/m11./s1

HIDE SMILES / InChI

Molecular Formula Mg
Molecular Weight 24.305
Charge 2
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C25H23FNO4
Molecular Weight 420.4528
Charge -1
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 2 / 2
E/Z Centers 1
Optical Activity UNSPECIFIED

Description

Pitavastatin is a new synthetic 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoA reductase) inhibitor, which was developed, and has been available in Japan since July 2003. Metabolism of pitavastatin by the cytochrome P450 (CYP) system is minimal, principally through CYP 2C9, with little involvement of the CYP 3A4 isoenzyme, potentially reducing the risk of drug-drug interactions between pitavastatin and other drugs known to inhibit CYP enzymes. To date, human and animal studies have shown pitavastatin to be potentially as effective in lowering LDL-cholesterol levels as rosuvastatin. Pitavastatin under the trade name Livalo is indicated as an adjunctive therapy to diet to reduce elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), triglycerides (TG), and to increase HDL-C in adult patients with primary hyperlipidemia or mixed dyslipidemia. Pitavastatin competitively inhibits HMG-CoA reductase, which is a rate-determining enzyme involved with biosynthesis of cholesterol, in a manner of competition with the substrate so that it inhibits cholesterol synthesis in the liver. As a result, the expression of LDL-receptors followed by the uptake of LDL from blood to liver is accelerated and then the plasma TC decreases. Further, the sustained inhibition of cholesterol synthesis in the liver decreases levels of very low density lipoproteins. Common statin-related side effects (headaches, stomach upset, abnormal liver function tests and muscle cramps) were similar to other statins.

CNS Activity

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1.7 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
LIVALO
Primary
LIVALO
PubMed

PubMed

TitleDatePubMed
Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB.
2002 Jan 11
Contribution of vascular NAD(P)H oxidase to endothelial dysfunction in heart failure and the therapeutic effects of HMG-CoA reductase inhibitor.
2004 Nov
Bile salt export pump (BSEP/ABCB11) can transport a nonbile acid substrate, pravastatin.
2005 Aug
Effect of pitavastatin on transactivation of human serum paraoxonase 1 gene.
2005 Feb
Involvement of BCRP (ABCG2) in the biliary excretion of pitavastatin.
2005 Sep
Modulation of celecoxib- and streptozotocin-induced experimental dementia of Alzheimer's disease by pitavastatin and donepezil.
2008 Mar
Effects of statins on adipose tissue inflammation: their inhibitory effect on MyD88-independent IRF3/IFN-beta pathway in macrophages.
2008 May
Synthesis and HMG-CoA reductase inhibition of 2-cyclopropyl-4-thiophenyl-quinoline mevalonolactones.
2009 Dec 1
Functional characterization of mouse organic anion transporting peptide 1a4 in the uptake and efflux of drugs across the blood-brain barrier.
2010 Jan
Co-administration of ezetimibe enhances proteinuria-lowering effects of pitavastatin in chronic kidney disease patients partly via a cholesterol-independent manner.
2010 Jan
Regulation mechanism of ABCA1 expression by statins in hepatocytes.
2011 Jul 15
Pharmacokinetic interaction between pitavastatin and valsartan: a randomized, open-labeled crossover study in healthy male Korean volunteers.
2012 Apr
Comparison of the safety, tolerability, and pharmacokinetic profile of a single oral dose of pitavastatin 4 mg in adult subjects with severe renal impairment not on hemodialysis versus healthy adult subjects.
2012 Jul
Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11).
2013 Dec
Detection of statin cytotoxicity is increased in cells expressing the OATP1B1 transporter.
2013 Jul
ATP-dependent transport of statins by human and rat MRP2/Mrp2.
2013 Jun 1
Patents

Sample Use Guides

In Vivo Use Guide
1 to 4 mg orally once daily at any time of the day with or without food. The recommended starting dose is 2 mg and the maximum dose is 4 mg
Route of Administration: Oral
In Vitro Use Guide
The liver cancer cells Huh-7 and SMMC7721 were trypsinized into single cells and split into 24-well dishes at 100 cells/well. The cells were pretreated with 0 µM, 0.5 µM, or 1 µM of pitavastatin and cultured for 8 days. Pitavastatin treatment increased the population of Huh-7 cells in the sub-G1 phase. It induced apoptosis of liver cancer cells. It was found that caspase-9 and caspase-3 as well as poly ADP ribose polymerase (PARP) were cleaved.
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:12:04 UTC 2019
Edited
by admin
on Mon Oct 21 20:12:04 UTC 2019
Record UNII
BDS8LUQ384
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PITAVASTATIN MAGNESIUM
Common Name English
PITAVASTATIN MAGNESIUM [WHO-DD]
Common Name English
(T-4)-BIS((3R,5S,6E)-7-(2-CYCLOPROPYL-4-(4-FLUOROPHENYL)-3-QUINOLINYL)-3-(HYDROXY-.KAPPA.O)-5-HYDROXY-6-HEPTENOATO-.KAPPA.O-)MAGNESIUM
Systematic Name English
ZYPITAMAG
Brand Name English
6-HEPTENOIC ACID, 7-(2-CYCLOPROPYL-4-(4-FLUOROPHENYL)-3-QUINOLINYL)-3,5-DIHYDROXY-, MAGNESIUM SALT (2:1), (3R,5S,6E)-
Systematic Name English
MAGNESIUM, BIS((3R,5S,6E)-7-(2-CYCLOPROPYL-4-(4-FLUOROPHENYL)-3-QUINOLINYL)-3-(HYDROXY-.KAPPA.O)-5-HYDROXY-6-HEPTENOATO-.KAPPA.O-)-, (T-4)-
Systematic Name English
Code System Code Type Description
CAS
956116-90-8
Created by admin on Mon Oct 21 20:12:04 UTC 2019 , Edited by admin on Mon Oct 21 20:12:04 UTC 2019
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY