Background:

GSK1324726A is a selective small molecule inhibitor of BET proteins with IC50 values of 41nM, 31nM and 22nM, respectively for BRD2, BRD3 and BRD4 [1].

GSK1324726A competes with histone H4 peptides for binding to the bromodomains of the BET proteins. It notably inhibits cell growth in neuroblastoma cell lines with a median GI50 value of 75nM. And it is also found to cause some level of net cell death. The mechanism of this is that GSK1324726A induces cytotoxicity in these cell lines. Treatment of GSK1324726A results in an induction of G1 arrest in SK–N-AS, SK–N–SH and CHP-212 cell lines. Meanwhile, caspase 3/7 induction is observed in SK–N–SH and CHP-212 cell lines. In mice bearing the neuroblastoma xenografts, GSK1324726A also shows the potency of inhibiting tumor growth [1].

参考文献:
[1] Wyce A, Ganji G, Smitheman KN, Chung CW, Korenchuk S, Bai Y, Barbash O, Le B, Craggs PD, McCabe MT, Kennedy-Wilson KM, Sanchez LV, Gosmini RL, Parr N, McHugh CF, Dhanak D, Prinjha RK, Auger KR, Tummino PJ. BET inhibition silences expression of MYCN and BCL2 and induces cytotoxicity in neuroblastoma tumor models. PLoS One. 2013 Aug 23;8(8):e72967.