Target discovery for new antitubercular drugs using a large dataset of growth inhibitors from PubChem.

Target discovery for new antitubercular drugs using a large dataset of growth inhibitors from PubChem. Infect Disord Drug Targets. 2018 Dec 05;: Authors: Goldman RC Abstract The number of drugs available for treatment of active tuberculosis are diminishing due to increased multidrug resistance selection in Mycobacterium tuberculosis leading to multiple (MDR) and extensively (XDR) resistant strains. Also, TB is treated with multiple drugs to minimize further resistance development, mandating a sustained effort to identify new lead compounds for treating drug resistant TB, and shortening time to cure for all TB infections. High throughput screening, a well-known approach to discovery of new leads, is conducted in two basic modes 1) using whole cells and screening for inhibition of growth, or whole cell reporter cells that signals when a specific pathway is perturbed, and 2) in vitro non-cell based enzyme or other functional assays for direct ligand-target binding. Combining high throughput screening for inhibitors of growth (to identify and chemically assess inhibitors active on whole cells), followed by target identification abrogates the problem of discovering new leads in non-cell based systems that are inactive on whole cells due to issues with target access (e.g., uptake). High throughput screening of 341,778 compounds by the National Institutes of Health identified 8,950 primary hit, growth inhibitors of M. tuberculosis. Final ev...
Source: Infectious Disorders Drug Targets - Category: Infectious Diseases Authors: Tags: Infect Disord Drug Targets Source Type: research