Contact: the NCATS Chemical Genomics Center Team
Library Size: 100K compounds
Format: 1536-well plates in dose-response format
Availability: Accessed through collaboration with NCATS
Genesis Chemical Library: NCATS has been assembling a high-value, modern chemical library that contains more than 100,000 compounds and will grow over the course of the next few years. The collection is plated in 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.