Search of small molecule agonist for GPR120 using de novo modelling approach

Abstract

Thesis entitled quotSearch of small molecule agonist for GPR120 using de-novo modelling approachquot describes a theoretical methodology and study on human GPR120 protein. We hope that this work will help to fill gaps in the field of computational approaches for the development of new GPR120 agonists. In the past few years free fatty acid receptor class has been explored as an attractive therapeutic target for the treatment of type-2 diabetes and metabolic disease. GPR120 (free fatty acid receptor 4) is an important member of this class and counter act on the type-2 diabetes associated risks like, obesity, insulin resistance, cardiac protective role etc. Ever since its discovery a race is started to find a suitable clinical candidate but not much success has been achieved. Recently in 2014, an isohumulone compound from hops extract was found to show moderate GPR120 agonist activity and partially active on PPARand#947; as well. However, during the phase II clinical trials, compound did not show expected pharmacokinetic results hence, withdrawn. This thesis describes in detail the application of structure and ligand-based computational methods for better understanding of the structure-function relationship of GPR120 agonists. Further the outcomes were successfully applied in rational design of the GPR120 small molecule agonist. newline