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NEWS: Development of Kinase Chemogenomic Set Reaches Milestone

Sep 6, 2017

Investigators at the University of North Carolina at Chapel Hill Structural Genomics Consortium (SGC-UNC)—in partnership with the DiscoverX Corporation—have reached the halfway point in their development of a potent group of inhibitors which allow deeper exploration of the human kinome, dubbed the Kinase Chemogenomic Set. Findings from the new study—published recently in PLOS ONE through an article entitled “Progress towards a public chemogenomic set for protein kinases and a call for contributions”— should help the scientific community better understand the role the kinome plays in human disease. By building this selective set of compounds and making it freely available, UNC-Chapel Hill and its partners are offering the and the ability to collaborate on the discovery and advancement of new therapies.

"Through our collaboration with DiscoverX, we screened a large set of compounds that we call Published Kinase Inhibitor Set 2, and these results allowed us to reach the halfway point in constructing the KCGS" explained lead study investigator David Drewry, Ph.D., a research associate professor at the UNC Eshelman School of Pharmacy. "To mark this milestone and in keeping with our mission of open science, we are releasing these results into the public domain. We sincerely thank all of our co-author partners whose vision, generosity and hard work make the construction of this set possible."

The kinome, made up of enzymes called kinases, provides a tremendous opportunity for drug discovery. While more than 30 kinase inhibitors have been approved for the treatment of disease, the kinome has been largely unexplored until SGC-UNC, DiscoverX and other SGC partner companies embarked on this project. Findings from the new study also contain the results of screening each compound in PKIS2 against the DiscoverX panel of more than 400 kinase assays.

PKIS2 is a collection of more than 500 kinase inhibitors donated by GSK, Pfizer, and Takeda Pharmaceuticals that SGC-UNC makes available to the scientific community. The kinome wide annotation of inhibition profiles allows users of the set to interpret their results more readily.

"We have shown how well each of the PKIS2 compounds inhibits each of the kinases DiscoverX screens," Dr. Drewry noted. "Researchers to whom we have given access to PKIS2 can use that information. They will know that compound X inhibits kinases A, B, and C, but compound Z inhibits kinases D, and E. With such a big data set people can easily find compounds of particular interest to them and know that the compounds are annotated with near full-kinome inhibition data."

This collaborative project between industrial and academic scientists will continue to expand the KCGS with the goal of fully covering all human protein kinases. Dr. Drewry and his fellow scientists aim to ensure the therapeutic potential of as many protein kinases as possible will be uncovered. The expansion of the KCGS, combined with its use in diverse disease-relevant phenotypic screens and the sharing of the resulting data in the public domain, is the best mechanism for reaching this goal.