WH25244-NC

WH25244-NC is a negative control compound for the PROTAC (Proteolysis-Targeting Chimera) WH25244, which is designed to target Bcl-2 and Bcl-xL for degradation. WH25244-NC is structurally similar to WH25244 but is modified to lack the ability to recruit the VHL E3 ligase. While it retains the binding affinity for Bcl-2 and Bcl-xL (derived from the dual inhibitor navitoclax), it cannot induce the ubiquitination and subsequent proteasomal degradation of these proteins. It is used in preclinical research, specifically in studies involving venetoclax-resistant chronic lymphocytic leukemia (CLL), to demonstrate that the biological activity of WH25244 is dependent on its ability to degrade its targets rather than simple occupancy-based inhibition or non-specific effects.