Strategic Expansion and Management of Chemical Libraries for Drug Discovery

Abstract

The extensive chemical space provides options of selecting molecules that are unique and diverse to build a truly custom made screening chemical library. Finding the right compound from a high-throughput screening (HTS) that could be optimized to a drug candidate is no simple task. Selecting meaningful compounds from a multitude of commercially available compounds is critical; over the years Institut Pasteur Korea (IPK), whose mission is to eliminate the global threat of infectious disease, had built a selected chemical library of commercially available and proprietary compounds sensitive to encompass structural diversity aspect. To obtain structural diversity, lead-like Bemis-Murcko substructures were generated from IPK legacy collections, and those compounds with different Bemis-Murcko substructures were selected. Furthermore, structural fingerprints were used to select diverse subsets of compounds. Based on the analyses of whole structures and substructures, we selected a diverse set to utilize against several infectious diseases models provided at IPK. We implemented a strategic approach to managing the chemical library by taking into consideration the stability of compounds while maintaining compounds integrity. Automated liquid handlers were used to compress and replicate the chemical libraries into various concentrations. Emerging infectious diseases are on the rise and unpredictable in the global health landscape; using unique and carefully selected compounds for screening can make a difference in finding our next drug candidate at IPK.

A combination screening to identify enhancers of para-aminosalicylic acid against Mycobacterium tuberculosis

“…DMSO, rifampicin and PAS (catalog number A79604; lot number BCBS7659V) were purchased from Sigma-Aldrich Korea (Yongin, South Korea). Screening compounds were selected from commercial vendor libraries, based on novelty, drug likeness and absence of redundancy with compounds already tested internally in our laboratory 30 . A total of 104,783 small molecules were assembled, including 51,406 compounds from Enamine and 53,377 compounds from various suppliers: ChemDiv (12,270), ChemBridge (11,709), Life Chemicals (7917), Vitas-M (5000), Princeton BioMolecular Research (4751), InterBioScreen (3436), Otava Chemicals (3366), Thermo Fisher Scientific (Maybridge collection, 2951) and Specs (1977).…”

4‐(2‐Hydroxyethyl)‐1‐piperazine ethane sulfonic acid repositioning: Amyloid disaggregating agent and its sustained‐release system

“…8 The solubility is the most important physicochemical property for the new drug discovery. 9,10 The partition coefficient (P) indicates the tendency of a neutral compound to dissolve in an immiscible biphasic system between water and lipids such as fats, oils, and organic solvents. Basically, it measures how much solute dissolves in the water and organic fractions.…”