Biology subjects

Elkins, J. M.

Publications and source records attributed to Elkins, J. M..

4 recordsLinked to original sources

bioRxiv2018

SGC-GAK-1: a chemical probe for cyclin G associated kinase (GAK)

We describe SGC-GAK-1 (11), a potent, selective, and cell-active inhibitor of cyclin G associated kinase (GAK), together with a structurally-related negative control SGC-GAK-1N (14). SGC-GAK-1 is highly selective in a kinome-wide screen, but cellular engagement assays defined RIPK2 as a collateral target. We identified 18 as a potent inhibitor of RIPK2 lacking GAK activity. Together, the chemical probe set of 11, 14, and 18 can be used to interrogate the cellular biology of GAK inhibition.

cell biology↗

bioRxiv2017

Identification and Optimization of 4-Anilinoquinolines as Inhibitors of Cyclin G Associated Kinase

4-Anilinoquinolines were identified as potent and narrow spectrum inhibitors of the cyclin G associated kinase (GAK), an important regulator of viral and bacterial entry into host cells. Optimization of the 4-anilino group and the 6,7-quinoline substituents produced GAK inhibitors with nanomolar activity and over 50,000-fold selectivity relative to other members of the numb-associated kinase (NAK) sub-family. These compounds may be useful tools to explore the therapeutic potential of GAK in prevention of a broad range of infectious diseases.

pharmacology and toxicology↗

bioRxiv2017

Progress Towards a Public Chemogenomic Set for Protein Kinases and a Call for Contributions

Protein kinases are highly tractable targets for drug discovery. However, the biological function and therapeutic potential of the majority of the 500+ human protein kinases remains unknown. We have developed physical and virtual collections of small molecule inhibitors, which we call chemogenomic sets, that are designed to inhibit the catalytic function of almost half the human protein kinases. In this manuscript we share our progress towards generation of a comprehensive kinase chemogenomic set (KCGS), release kinome profiling data of a large inhibitor set (Published Kinase Inhibitor Set 2 (PKIS2)), and outline a process through which the community can openly collaborate to create a KCGS that probes the full complement of human protein kinases.

pharmacology and toxicology↗

bioRxiv2016

Development of Narrow Spectrum ATP-competitive Kinase Inhibitors as Probes for BIKE and AAK1

Understanding the structural determinants of inhibitor selectivity would facilitate the design and preparation of kinase probes. We describe a pair of matched compounds differing only by one degree of saturation but showing dramatic differential activities at select kinases. We utilized x-ray crystallography and computational analysis to rationalize the basis of the differential activity.

pharmacology and toxicology↗