Delving into the Latest Updates on BRL-48482 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

PPARγ

Mechanism

PPARγ agonists(Peroxisome proliferator-activated receptor γ agonists), Insulin sensitizers

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication-

Inactive Indication

Diabetes Mellitus, Type 2

Originator Organization

Smithkline Beecham Pharmaceuticals (India) Ltd.

Active Organization-

Inactive Organization

Smithkline Beecham Pharmaceuticals (India) Ltd.

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

Structure

Molecular FormulaC20H19N3O4S

InChIKeyZYKPNHFCNSVFNF-UHFFFAOYSA-N

CAS Registry122320-46-1

Liver-type fatty acid binding protein (L-FABP) has been proposed to be involved in the transport of fatty acids and peroxisome proliferators from the cytosol into the nucleus for interaction with the peroxisome proliferator-activated receptors (PPARs). On the basis of this premise, we investigated by isothermal titration calorimetry the binding of myristic, stearic, oleic, and docosahexaenoic acids to three orthologous L-FABPs and compared these results to those obtained for several xenobiotics [Wy14,643, bezafibrate, 5,8,11,14-eicosatetraynoic acid (ETYA), and BRL48,482] known for their peroxisome proliferating activity in rodents. Recombinant human, murine, and bovine L-FABPs were analyzed and the thermodynamic data were obtained. Our studies showed that fatty acids bound with a stoichiometry of 2:1, fatty acid to protein, with dissociation constants for the first binding site in the nanomolar range. With dissociation constants above 1 microM the drug peroxisome proliferators showed weaker binding, with the exception of arachidonate analogue ETYA, which bound with a similar affinity as the natural fatty acid. Some of the thermodynamic data obtained for fatty acid binding could be explained by differences in protein structure. Moreover, our results revealed that binding affinities were not determined by ligand solubility in the aqueous phase.

100 Deals associated with BRL-48482

Login to view more data