High Throughput Screening for Tuberculosis at NCL : A Novel Drug Discovery Initiative from CSIR 73rd CSIR Foundation Day Laxman Nawale, Hardik Manek, Nandadeep Jadhav, Jennifer Cheruvathur, Dhiman Sarkar* Combi Chem-Bio Resource Center, OCD, National Chemical Laboratory, Pune - 411 008 *E-mail : d.sarkar@ncl.res.in; lu.nawale@ncl.res.in CSIR was founded on 26 September 1942, by a resolution of the then Central Legislative Assembly. The R & D activities of CSIR includes various fields such as aerospace engineering, Structural engineering, ocean sciences, molecular biology, metallurgy, chemicals, mining, food, petroleum, leather, and environment. Introduction Library Screening Infrastructure Figure 1.a. Integrated NRM Inventory Management Why do we need new Tuberculosis drugs? Transmission Drug discovery on Shoestring Figure 1.b. Functional Cell-based Assays for Targeted Lead Discovery in High-throughput Screening Figure 1.c. In vitro ADMET Parameter Assessment Figure 1. Schematic representation of High-Throughput Screening and Data Analysis in development of the NRM HTS library Step towards identification of TB drugs Natural products (150) Synthetic compounds (5800) Nano particles (50) 10 In vitro assays 15 Lead molecules (5 Scaffold) Hit follow-up 6000 Compounds (300 Scaffold) Our Focus Discover and develop novel drugs that are effective at curing latent, drug sensitive and drug resistant TB Study the biology of tuberculosis bacilli in great detail to identify new metabolic pathways that may be vulnerable to drugs Test thousands of potential drugs in our screening facility to find new compounds or new compound classes that kill TB bacteria Increase throughput up to 20,000 compounds at a time Develop novel screens using conditions that mimic those the TB bacteria encounters in the human body Utilize medical chemistry to optimize the structures of compounds so that they kill TB bacteria in a more potent fashion and are non-toxic Meet the challenges from industry Acknowledgement Authors are thankful to Director, NCL, Pune, India for providing financial assistance through NORMS (CSC 0406) project. Figure 2. High-throughput Screening for Targeted small-molecule lead discovery