Screening of Leptin-LepR modulators using molecular docking and binding assay

TL;DR

This study identifies compounds that can modulate the Leptin-LepR complex, offering potential therapeutic strategies for diseases involving this interaction.

Contribution

The study introduces a novel approach combining molecular docking and binding assays to identify Leptin-LepR modulators.

Findings

18 compounds were identified as potential modulators of the Leptin-LepR complex.

Six compounds showed significant modulation of complex formation in ELISA assays.

The findings suggest new therapeutic strategies for diseases involving Leptin-LepR deregulation.

Abstract

Leptin is a pleiotropic hormone which, upon binding to its cognate leptin receptor (LepR), induces the activation of the JAK2/ERK,
STAT3/STAT5 and IRS/PI3 kinase signaling cascades. Hence, we used molecular docking and a chemical library to identify 18 compounds with
high probability of interacting with the leptin binding domain (LBD) of LepR. 6 out of 18 compounds were selected based on toxicological
and physicochemical properties to evaluate their effect in the formation of Leptin-LepR complex using ELISA assays. The six compounds
showed discreet but significant modulation on the complex formation. These results have important implications in proposing novel
strategies for modulating the formation of the Leptin-LepR complex, as therapeutic alternatives for patho-physiologies where the
formation of this complex is deregulated.