GCN2iB鏄叿鏈堿TP绔炰簤鎬х殑銆佷竴绉嶄笣姘ㄩ吀/鑻忔皑閰歌泲鐧芥縺閰垛€斺€斿帇鍔涘簲绛旀縺閰?GCN2)鐨勬姂鍒跺墏锛屽叾IC50鍊间负2.4nM銆侟br>CAS锛?183470-12-2
鍒嗗瓙寮忥細C18H12ClF2N5O3S
鍒嗗瓙閲忥細451.83
绾害锛?8%
瀛樺偍锛歋tore at -20掳C

Background:

GCN2iB is an ATP-competitive inhibitor of a serine/threonine-protein kinase general control nonderepressible 2 (GCN2), with an IC50 of 2.4 nM.

GCN2iB shows an IC50 value of 2.4 nM for GCN2 and potent cellular activity. In a panel of 468 kinases, only GCN2 shows >99.5% inhibition, and three kinases (MAP2K5, STK10, and ZAK) show >95%inhibition at 1 渭M GCN2iB, demonstrating high kinase selectivity[1].

In the antitumor activity study of the CCRF-CEM xenografts, ASNase or GCN2iB alone does not significantly affect tumor growth. Notably, a combination of ASNase and GCN2iB elicit potent antitumor activity (P=0.0002) with synergistic effects. In MV-4-11 and SU.86.86 xenografts, robust antitumor activity of the combination of GCN2iB and ASNase is observed with synergistic effect, respectively. ASNase/GCN2iB-treated tumors do not show significant growth even after drug cessation. The combination of ASNase and GCN2iB yield survival advantage compared with the vehicle treated control with synergistic effect[1].

[1]. Nakamura A, et al. Inhibition of GCN2 sensitizes ASNS-low cancer cells to asparaginase by disrupting the amino acid response. Proc Natl Acad Sci U S A. 2018 Aug 14;115(33):E7776-E7785.