A collaboration between SGC and the Centre for Integrative Chemical Biology and Drug Discovery (CICBDD) at the University of North Carolina has resulted in UNC6934, a chemical probe for NSD2-PWWP1. UNC6934 is a potent antagonist of NSD2-PWWP1 with a Kd (SPR) of 80 ± 18 nM and is selective for NSD2-PWWP1 over 14 other PWWP domains including NSD3-PWWP1, the closest on the phylogenetic tree.
UNC6934 disrupts the NSD2-PWWP1 interaction with H3K36me2 nucleosomes in U2OS cells as measured by a NanoBret assay with an IC50 of 1.09 ± 0.23 microM. UNC7145, a closely-related control compound, with an iso-propyl group replacing a cyclo-propyl group, is inactive by SPR and NanoBret assays.
Data relating to the discovery of this probe is being prepared for publication. In the meantime, in order to facilitate research by the community we are making this compound available through this website.