DDIS-27. TARGETING ATP DOCKING AND P35/P25 BINDING OF CDK5 IN GLIOMA STEM CELLS USING SYNTHETIC INHIBITORS

ABSTRACT: Abstract The survival advantage of glioma stem cells (GSCs) represents a critical mechanism for growth, therapy resistance and recurrence in glioblastoma. So far, targeting GSCs has not been highly specific, since these cells co-opt the normal developmental signaling pathways. We have demonstrated that the activated CDK5-CREB1 signaling axis regulates GSC self-renewal and also promotes radiation-resistance. Thus targeting CDK5 signaling is highly rational, yet there are challenges. Most of the available CDK5 inhibitors also target other CDKs non-specifically. In collaboration with The Center for Molecular Evolution and Drug Discovery, we are developing novel CDK5 inhibitors that are highly potent and specific. METHODOLOGY: The CKD5-p25 crystal structure (pdb code 1UNL) was used to conduct

SUBMITTER: Mukherjee S 

PROVIDER: S-EPMC6846902 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature