A Potent and Selective CDKL5/GSK3 Chemical Probe is Neuroprotective

• DOI: 10.1101/2023.02.09.527935
• Publication Date: 2023-02-10T18:25:15Z
• Authors: Han Wee Ong; Yi Liang; William Richardson; Emily R. Lowry; Carrow I. Wells; Xiangrong Chen; Margaux Silvestre; Kelvin Dempster; Josie A. Silvaroli; Jeffery L. Smith; Hynek Wichterle; Navjot S. Pabla; Sila K. Ultanir; Alex N. Bullock; David H. Drewry; Alison D. Axtman
• Keywords: 0303 health sciences; 03 medical and health sciences; Article

Despite mediating several essential processes in the brain, including during development, cyclin-dependent kinase-like 5 (CDKL5) remains a poorly characterized human protein kinase. Accordingly, its substrates, functions, and regulatory mechanisms have not been fully described. We realized that availability of potent selective small molecule probe targeting CDKL5 could enable illumination roles normal development as well diseases where it has become aberrant due to mutation. prepared analogs AT-7519, known inhibitor cyclin dependent kinases advanced into Phase II clinical trials. identified analog