Identification of novel multitargeted PPARα/γ/δ pan agonists by core hopping of rosiglitazone

21Citations
Citations of this article
27Readers
Mendeley users who have this article in their library.

Abstract

The thiazolidinedione class peroxisome proliferator-activated receptor gamma (PPARγ) agonists are restricted in clinical use as antidiabetic agents because of side effects such as edema, weight gain, and heart failure. The single and selective agonism of PPARγ is the main cause of these side effects. Multitargeted PPARα/γ/δ pan agonist development is the hot topic in the antidiabetic drug research field. In order to identify PPARα/γ/δ pan agonists, a compound database was established by core hopping of rosiglitazone, which was then docked into a PPARα/γ/δ active site to screen out a number of candidate compounds with a higher docking score and better interaction with the active site. Further, absorption, distribution, metabolism, excretion, and toxicity prediction was done to give eight compounds. Molecular dynamics simulation of the representative Cpd#1 showed more favorable binding conformation for PPARs receptor than the original ligand. Cpd#1 could act as a PPARα/γ/δ pan agonist for novel antidiabetic drug research.

Cite

CITATION STYLE

APA

Wang, X. J., Zhang, J., Wang, S. Q., Xu, W. R., Cheng, X. C., & Wang, R. L. (2014). Identification of novel multitargeted PPARα/γ/δ pan agonists by core hopping of rosiglitazone. Drug Design, Development and Therapy, 8, 2255–2262. https://doi.org/10.2147/DDDT.S70383

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free