The Kinase Chemogenomic Set (KCGS): An Open Science Resource for Kinase Vulnerability Identification.

Area of Science:

• Biochemistry
• Pharmacology
• Molecular Biology

Background:

• Protein kinases play crucial roles in cellular signaling pathways, and dysregulation is implicated in various diseases.
• Developing selective inhibitors is essential for dissecting kinase functions and for therapeutic development.
• Existing inhibitor sets may lack comprehensive annotation or selectivity for broad research applications.

Purpose of the Study:

• To assemble and annotate a chemogenomic set of highly selective protein kinase inhibitors.
• To provide an open science resource for researchers studying kinase biology and signaling.
• To facilitate cell-based screening assays with well-characterized kinase inhibitors.

Main Methods:

• Curated a collection of protein kinase inhibitors based on biochemical assay screening data.
• Ensured inhibitors exhibit potent activity and a narrow spectrum of kinase inhibition.
• Annotated the inhibitor set with detailed information on target kinases and selectivity profiles.

Main Results:

• Assembled the kinase chemogenomic set (KCGS) Version 1.0, comprising 187 inhibitors.
• The set covers 215 distinct human kinases.
• The KCGS is the most highly annotated collection of selective kinase inhibitors currently available.

Conclusions:

• The KCGS provides a valuable, open-access resource for advancing kinase biology research.
• Its high selectivity and annotation enable more precise investigations into kinase function.
• This resource is expected to accelerate drug discovery and the understanding of kinase-driven diseases.