1. 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 *
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