WDR5-IN-1

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].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Histone Methyltransferase

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]. Cell Cycle Analysis[1] Cell Line: MV4:11 cells Concentration: 1 µM Incubation Time: 48 hours Result: Showed an approximate 4 fold increased SubG1 cells. Western Blot Analysis[1] Cell Line: MV4:11 cells Concentration: 0.01, 0.03, 0.1, 0.3, 1, 3 µM Incubation Time: 24, 48 hours Result: p53 and p21 protein levels started to increase from 8 h post treatment of compound 16 at 300 nM and continued to elevate up to 32 h.

[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.