WDR5-IN-1 is a potent and selective WD repeat domain 5 (WDR5) inhibitor, with a Kd of <0.02 nM. WDR5-IN-1 inhibits MLL1 histone methyltransferase (HMT) activity with an IC50 of 2.2 nM. WDR5-IN-1 diminishes MYC recruitment at WDR5-displaced genes and exhibits potent anti-proliferative effects in CHP-134 (neuroblastoma) and Ramos (Burkitt’s lymphoma) lines[1].
WDR5-IN-1 (1 µM; 48 hours) shows an apparent decrease in G2M phase cells[1].WDR5-IN-1 (0.01-3 µM; 24-48 hours) increases p53 and p21 protein levels[1].WDR5-IN-1 shows anti-proliferative activity in MYC-driven cancers (CHP-134, Ramos, Raji, Daudi, SW620, SW480 cells), with GI50s ranging from 0.26-3.2 µM[1].
[1]. Tian J, et al.Discovery and Structure-Based Optimization of Potent and Selective WD Repeat Domain 5 (WDR5) Inhibitors Containing a Dihydroisoquinolinone Bicyclic Core.J Med Chem. 2020 Jan 23;63(2):656-675.