NAVEGLITAZAR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H26O6
Molecular Weight	422.4703
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CO[C@@H](CC1=CC=C(OCCCOC2=CC=C(OC3=CC=CC=C3)C=C2)C=C1)C(O)=O

InChI

InChIKey=OKJHGOPITGTTIM-DEOSSOPVSA-N

InChI=1S/C25H26O6/c1-28-24(25(26)27)18-19-8-10-20(11-9-19)29-16-5-17-30-21-12-14-23(15-13-21)31-22-6-3-2-4-7-22/h2-4,6-15,24H,5,16-18H2,1H3,(H,26,27)/t24-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C25H26O6
Molecular Weight	422.4703
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://adisinsight.springer.com/drugs/800015313 | https://www.ncbi.nlm.nih.gov/pubmed/17012539

Naveglitazar is an oral dual peroxisome proliferator-activated receptor (PPAR) agonist, which was under development with Ligand Pharmaceuticals for the treatment of type 2 diabetes mellitus. Naveglitazar is a nonthiozolidinedione peroxisome proliferator-activated receptor (PPAR) α-γ dual, γ-dominant agonist that has shown glucose-lowering potential in animal models and in the clinic. Naveglitazar had been in phase II clinical trials for the once-daily oral treatment of type 2 diabetes, however, the development was discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Peroxisome proliferator-activated receptor alpha 62 Target ID: CHEMBL239 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19700659	Agonist 2678		1.71 µM [IC50]
Peroxisome proliferator-activated receptor gamma 111 Target ID: CHEMBL235 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19700659	Agonist 2678		0.024 µM [IC50]

PubMed

Title	Date	PubMed
The disposition and metabolism of naveglitazar, a peroxisome proliferator-activated receptor alpha-gamma dual, gamma-dominant agonist in mice, rats, and monkeys.	2007 Jan	17012539
Rat Urinary Bladder Carcinogenesis by Dual-Acting PPARalpha + gamma Agonists.	2008	19197366
Cross-Species Differential Plasma Protein Binding of MBX-102/JNJ39659100: A Novel PPAR-gamma Agonist.	2008	18815616
Urothelial carcinogenesis in the urinary bladder of rats treated with naveglitazar, a gamma-dominant PPAR alpha/gamma agonist: lack of evidence for urolithiasis as an inciting event.	2008 Feb	18474944
Allometric prediction of the human pharmacokinetic parameters for naveglitazar.	2008 Jul-Sep	19007045
Neoplastic and non-neoplastic changes in F-344 rats treated with Naveglitazar, a gamma-dominant PPAR alpha/gamma agonist.	2009 Oct	19700659

Patents

Sample Use Guides

In Vivo Use Guide

The carcinogenic potential of naveglitazar, a gamma-dominant peroxisome proliferator-activated receptor (PPAR) alpha/gamma dual agonist, was evaluated in a two-year study in F344 rats (0, 0.3, 1.0, or 3.0 mg/kg, males; 0, 0.1, 0.3, or 1.0 mg/kg, females). Rats were randomly assigned to treatment groups based on weight. Rats (60/sex/group) were assigned to groups receiving 0, 0.3, 1.0, or 3.0 mg naveglitazar/kg body weight/day (males) or 0, 0.1, 0.3, or 1.0 mg naveglitazar/kg body weight/day (females) by oral gavage.

Route of Administration: Oral

In Vitro Use Guide

In vitro, naveglitazar binds selectively to PPAR g with high affinity (IC50 =0.024 uM, Ki = 0.022uM) and to PPAR a with lower affinity (IC50 =1.71 uM, Ki = 1.66 uM)

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:18:40 GMT 2023` Edited by `admin` on `Fri Dec 15 16:18:40 GMT 2023`
Record UNII	Y995M7GM0G
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NAVEGLITAZAR

Official Name

English

(2S)-2-Methoxy-3-[4-[3-(4-phenoxyphenoxy)propoxy]phenyl]propanoic acid

Systematic Name

English

naveglitazar [INN]

Common Name

English

BENZENEPROPANOIC ACID, .ALPHA.-METHOXY-4-(3-(4-PHENOXYPHENOXY)PROPOXY), (.ALPHA.S)

Common Name

English

LY519818

Code

English

LY9818

Code

English

LY-519818

Code

English

NAVEGLITAZAR [USAN]

Common Name

English

LY-9818

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C98233