"目录号: HY-14817
Cell Cycle/DNA DamageNF-κB-
Indeglitazar 是一种具有口服活性的PPAR泛激动剂，对 PPAR 亚型 alpha (α)，delta (δ) 和 gamma (γ)都有作用活性。
PPAR
相关产品
GW9662-Rosiglitazone-Retinoic acid-Troglitazone-Pioglitazone hydrochloride-Elafibranor-GW 501516-CDDO-Im-Fenofibrate-T0070907-Wy-14643-GW0742-Daidzein-FH535-BMS-687453-
生物活性
Description
Indeglitazar is an orally available peroxisome proliferator-activated receptor (PPAR) pan-agonist for all three PPAR subtypes alpha (α), delta (δ) and gamma (γ).
IC50& Target
PPAR[1]
In Vitro
In an assay of preadipocyte differentiation, measuring in part functional insulin sensitization capability of the cells, Indeglitazar shows an EC50of 0.32 μM compared with Rosiglitazone, which shows an EC50of 13 nM, although the maximal response obtained from the 2 compounds is comparable[1].
In Vivo
An initial assessment of in vivo activity is carried out using the Zucker rat model of diabetes. The significant lowering of glucose, HbA1C, triglycerides, and total cholesterol are observed after i.v. treatment with 10 mg/kg Indeglitazar once per day for 3 weeks. Notably, the level of Adiponectin (on day 21) is essentially unchanged in treated vs. untreated animals (4.8 mcg/mL vs. 4.9 mcg/mL), thus the observed reductions in glucose and HbA1Care achieved in an adiponectin-independent fashion. These differences in the effects of Indeglitazar in vivo may be a consequence of synergy between the 3 PPAR activities or because of the SPPARM profile of the compound, or a combination of these factors. The oral activity of Indeglitazar is assessed in theob/obmodel of diabetes and insulin resistance. Indeglitazar significantly decreases glucose, insulin, triglycerides, and free fatty acid levels[1].
Clinical Trial
NCT00425919
Wyeth is now a wholly owned subsidiary of Pfizer
Diabetes Mellitus
January 2007
Phase 2
NCT00447629
Wyeth is now a wholly owned subsidiary of Pfizer
Diabetes Mellitus
January 2007
Phase 1
NCT00448032
Wyeth is now a wholly owned subsidiary of Pfizer
Diabetes Mellitus
November 2006
Phase 1
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References
[1].Artis DR, et al. Scaffold-based discovery of Indeglitazar, a PPAR pan-active anti-diabetic agent. Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):262-7.