Identification of novel peroxisome proliferator-activated receptor-gamma (PPAR[gamma]) agonists using molecular modeling method
MetadataShow full item record
Peroxisome proliferator-activated receptor-gamma (PPAR?) plays a critical role in lipid and glucose homeostasis. It is the target of many drug discovery studies, because of its role in various disease states including diabetes and cancer. Thiazolidinediones, a synthetic class of agents that work by activation of PPAR?, have been used extensively as insulin-sensitizers for the management of type 2 diabetes. In this study, a combination of QSAR and docking methods were utilised to perform virtual screening of more than 25 million compounds in the ZINC library. The QSAR model was developed using 1,517 compounds and it identified 42,378 potential PPAR? agonists from the ZINC library, and 10,000 of these were selected for docking with PPAR? based on their diversity. Several steps were used to refine the docking results, and finally 30 potentially highly active ligands were identified. Four compounds were subsequently tested for their in vitro activity, and one compound was found to have a K i values of <5 µM.
Showing items related by title, author, creator and subject.
Woo, C.; Loo, S.; Gee, V.; Yap, C.; Sethi, G.; Kumar, Alan Prem; Benny Tan, K. (2011)Thymoquinone (TQ), an active ingredient of Nigella sativa, has been reported to exhibit anti-oxidant, anti-inflammatory and anti-tumor activities through mechanism(s) that is not fully understood. In this study, we report ...
Isorhamnetin Inhibits Proliferation and Invasion and Induces Apoptosis through the Modulation of Peroxisome Proliferator-activated Receptor [gamma] Activation Pathway in Gastric CancerRamachandran, L.; Manu, K.; Shunmugam, M.; Feng, L.; Siveen, K.; Vali, S.; Kapoor, S.; Abbasi, T.; Surana, R.; Smoot, D.; Ashktorab, H.; Tan, P.; Ahn, K.; Yap, C.; Kumar, Alan Prem; Sethi, G. (2012)Gastric cancer (GC) is a lethal malignancy and the second most common cause of cancer-related deaths. Although treatment options such as chemotherapy, radiotherapy, and surgery have led to a decline in the mortality rate ...
Assessment of the pharmacokinetic profile of novel s-triazine derivatives and their potential use in treatment of Alzheimer's diseaseTrifunovic, J.; Borcic, V.; Vukmirovic, S.; Mikov, Momir (2017)© 2016 Elsevier Inc. Aims The current treatment of Alzheimer's disease is purely symptomatic. Scientists are looking for new treatment options which could alter the course of the disease and improve the quality of life ...