Chemical Probe Stories
Open access chemical probes have an impact on preclinical research!
OICR-9429 led to a preclinical candidate for treating leukemia.
2006: WDR5 apo structure deposited
2011-2014: Library screen, scaffold optimization, first-in-class WDR5 antagonist discovered and put in the public domain
2019: Celgene purchased rights to a preclinical candidate
The chemical probe inspires further research.
SMARCA2/4 BRD inhibitors lack efficacy killing SMARCA4-mutated cancers as suggested by genetic KO studies. When combined with an E3 ligase VHL ligand SMARCA2/4 inhibitors serve as potent PROTAC degraders such as ACBI-1, developed by Boehringer Ingelheim and the University of Dundee which phenocopied the RNAi results. Ref: U.S. Patent WO 2016138114 A1