Related Experiment Video
Updated: Mar 31, 2026

System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis
Published on: April 5, 2017
Optimization of Inhibitors of Mycobacterium tuberculosis Pantothenate Synthetase Based on Group Efficiency Analysis
Alvin W Hung1,2, H Leonardo Silvestre3, Shijun Wen1
1Department of Chemistry, University of Cambridge, Lensfield Rd, Cambridge, CB2 1EW, UK.
Abstract:
Ligand efficiency has proven to be a valuable concept for optimization of leads in the early stages of drug design. Taking this one step further, group efficiency (GE) evaluates the binding efficiency of each appendage of a molecule, further fine-tuning the drug design process. Here, GE analysis is used to systematically improve the potency of inhibitors of Mycobacterium tuberculosis pantothenate synthetase, an important target in tuberculosis therapy. Binding efficiencies were found to be distributed unevenly within a lead molecule derived using a fragment-based approach. Substitution of the less efficient parts of the molecule allowed systematic development of more potent compounds. This method of dissecting and analyzing different groups within a molecule offers a rational and general way of carrying out lead optimization, with potential broad application within drug discovery.
More Related Videos
10:29A High-throughput Compatible Assay to Evaluate Drug Efficacy against Macrophage Passaged Mycobacterium tuberculosis
Published on: March 24, 2017
09:57Visualization of the Charcoal Agar Resazurin Assay for Semi-quantitative, Medium-throughput Enumeration of Mycobacteria
Published on: December 14, 2016
Related Concept Videos
Methods of Medium Optimization
Catalytically Perfect Enzymes
Most enzymes...
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Turnover Number and Catalytic Efficiency
Chymotrypsin is a pancreatic enzyme that breaks down proteins during digestion....
Determination of Michaelis Constant and Maximum Elimination Rate
These parameters can be estimated by analyzing plasma concentration data post-drug administration. A notable example of this application is phenytoin, a drug with capacity-limited kinetics. It's recommended that phenytoin should be administered at two...
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes