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
Award Amount
$594,241.00
Ceiling
$594,241.00
Awarded
November 25, 2025
Identifier
5R01AI175342-03
The award funds research to develop and improve inhibitors targeting the enzyme lipoamide dehydrogenase in tuberculosis and non-tuberculous mycobacteria to combat drug resistance and improve treatment outcomes.
Description
This project focuses on exploring the enzyme lipoamide dehydrogenase (Lpd), a validated target in Mycobacterium tuberculosis (Mtb), to develop tight binding inhibitors (TBI). The study aims to analyze the binding interactions, improve inhibitor efficacy, and extend findings to non-tuberculous mycobacteria (NTM) pathogens. Objectives include defining structural features responsible for tight binding interactions of Lpd inhibitors, investigating the role of target residence time in antibacterial activity, developing analogs with improved pharmacokinetic properties, extending studies to NTM pathogens such as Mycobacterium avium and M. abscessus, and characterizing the structural organization of mycobacterial PDH complexes.