"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

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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.