ChemoDOTS: a web server to design chemistry-driven focused libraries

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Drug Discovery

Background:

• Hit-to-lead optimization is crucial in drug discovery, requiring iterative chemical modifications of initial hit compounds.
• Efficient generation of synthesizable chemical libraries is essential for exploring chemical space around a hit molecule.

Purpose of the Study:

• To introduce ChemoDOTS, a user-friendly web server designed to streamline hit-to-lead chemical optimization.
• To provide researchers with a tool for rapidly generating virtual chemical libraries with desired properties.

Main Methods:

• Users input an activated hit molecule and select reactive functions.
• The server suggests compatible chemical transformations based on industry-standard reactions.
• Automated coupling of building blocks, application of filters for physicochemical properties, and generation of stereoisomers, tautomers, and 3D conformers.

Main Results:

• ChemoDOTS enables rapid generation of large, diverse, and synthetically feasible chemical libraries.
• The generated virtual libraries are tailored with specific physicochemical properties.
• The output is compatible with docking software for virtual screening.

Conclusions:

• ChemoDOTS offers a powerful and accessible resource for hit-to-lead optimization in drug discovery.
• The web server simplifies the process of exploring chemical space and identifying lead candidates.