Chemical Libraries

Genesis: Modern Chemical Library to Enable Large-Scale Deorphanization of Novel Biological Mechanisms

Contact: Early Translation Branch     
Library Size: 100K compounds     
Format: 1,536-well plates in dose-response format     
Availability: Accessed through collaboration with NCATS

Description: Genesis Chemical Library: The collection is plated in quantitative high-throughput screening (qHTS) format, enabling large-scale deorphanization of unprecedented mechanisms. Bioactives identified from Genesis screening provide a high-quality starting point for medicinal chemistry optimization of proof-of-concept tool compounds or therapeutic leads. The library consists of more than 1,000 scaffolds that vary in representation from 20 to 100 compounds per chemotype. The modern nature of the library incorporates years of valuable lessons learned on chemical library design. A portion of the library includes many sp3-enriched chemotypes that are inspired by naturally occurring compounds. Such chemotypes retain the pharmacophore found in natural products while reducing the extreme complexity, making them synthetically tractable. The chemotype includes spirocyclic compounds as well as non-spiro novel chemotypes that either do not exist in literature or patent space or are scarcely found. This novelty provides a distinct advantage in the development of potential intellectual property, as well as providing opportunities for first-in-class compounds. Yet another feature of Genesis is that, given the need for rapid derivatization in medicinal chemistry, the library has been designed with core scaffolds that are purchasable commercially. This allows for optimization around what would otherwise be complex synthetic cores. Genesis’ compound space is largely non-overlapping with PubChem or any publicly available chemical library. Its overall library composition provides shape and electrostatic diversity while keeping known drug-like properties, such as solubility, lipophilicity, hydrogen bond donor/acceptor status and molecular weight, in check.

NPACT Chemical Library — Innovative Chemical Biology Library for Translational Sciences

Library Size: 11K compounds     
Format: 1,536-well and 384-well plates in dose-response format     
Availability: Accessed through collaboration with NCATS 

Description: NCATS Pharmacologically Active Chemical Toolbox (NPACT): NPACT is a world-class small molecule library of high-quality organism-agnostic and pharmacologically active agents, whether they are naturally occurring, nature inspired or synthetically created. The NPACT library consists of annotated compounds that inform on novel phenotypes, biological pathways and cellular processes. There are more than 7,000 mechanisms and phenotypes identified in the literature and worldwide patents that cover biological interactions within mammalian, microbial, plant and other model systems. The NPACT library of more than 11,000 compounds aims to cover as many of these biological mechanisms as possible, allowing for broad profiling of mechanism-to-phenotype associations. Many of the known mechanisms are represented by a few best-in-class compounds with non-redundant chemotypes that provide a diversity of physicochemical and pharmacological properties. The chemical classes include both synthetically derived small molecules and microbial- and plant-derived purified natural products. The clinical and basic research scope includes all quality-approved and investigational drugs, as well as all tool compounds that have varying degrees of validation as therapeutic or fundamental chemical biology approaches. NPACT continues to be dynamic and current with the state of translational research as new biological processes, mechanisms, and approaches are revealed in patents and literature.