GS-5829 (GS5829, Alobresib) is a novel potent, selective BET inhibitor.
GS-5829 dose-dependently induced apoptosis of CLL cells, 400 nM GS-5829 reduced the percentage of viable cells from 94.8% to 64.4%.
In XTT viability/proliferation assay, GS-5829 demonstrated more potency against MEC-1 CLL cells compared to JQ1 with IC50 of 46.4 nM.
GS-5829 inhibited CLL cell proliferation and induced leukemia cell apoptosis through deregulation of key signaling pathways, such as BLK, AKT, ERK1/2, and MYC.
GS-5829 also inhibited NF-κB signaling. GS-5829 significantly reduced c-Myc protein expression in ARK2 xenograft tumor samples, impaired USC-ARK2 xenograft tumor growth in vivo.
