SERP
Comments:
WM-3835 is an excellent chemical probe for HBO1. It should be used alongside its inactive control analog, WM-2474, whenever possible. Strengths of validation data include its robust SAR, nanomolar biochemical potency, strong evidence of target engagement (SPR, XR), and low micromolar cell activity. In terms of cellular activity, several readouts are consistent with engagement of its proposed target, including phenocopying the molecular and cellular effects of genetic depletion of HBO1 and reduction in the cellular H3K14ac biomarker. It has limitations in terms of efficacy in in vivo models due to its rapid metabolism, which the original report notes. While this represents the best quality HBO1 probe to-date (the results of excellent medicinal chemistry and cancer biology teamwork), additional validation data with respect to biochemical and cellular off-targets, as well as its effects on cellular health in additional models and cell lines, would add more confidence to its use.
(last updated:
26 Feb 2022 )