Award
NIH Reporter #5R01AI175342-03
Studies of lipoamide dehydrogenase tight binding inhibition in tuberculous and non-tuberculous mycobacteria
Recipient
Weill Medical College of Cornell University, New York, NY, United States
Award Amount
$594,241.00
Ceiling
$594,241.00
Awarded
November 25, 2025
Identifier
5R01AI175342-03
The award funds research to develop and analyze inhibitors targeting lipoamide dehydrogenase in tuberculosis and non-tuberculous mycobacteria to combat drug resistance and improve treatment.
Description
This project focuses on exploring the enzyme lipoamide dehydrogenase (Lpd), a validated but underexplored target in Mycobacterium tuberculosis (Mtb). The research aims to develop and analyze tight binding inhibitors (TBI) of Mtb Lpd through structure-guided analysis, enzyme kinetics, and binding assays. The goal is to understand the features responsible for tight binding interactions, improve inhibitor efficacy, and extend findings to non-tuberculous mycobacteria (NTM) pathogens such as Mycobacterium avium and M. abscessus. The study will explore structure-activity relationships (SAR), target vulnerability, and structural features of mycobacterial PDH complexes to develop novel whole-cell active inhibitors, ultimately contributing to the fight against TB and NTM diseases.