SU 9516

SU9516是一种3位取代的吲哚酮类CDK抑制剂，对CDK2，CDK1，和CDK4的IC50分别为22 nM，40 nM，和200 nM。 SU9516 decreases cdk2-specific phosphorylation of the retinoblastoma protein pRB, increases caspase-3 activation, and alters cell cycle in RKO and SW480 cells. SU9516 also inhibits the cell proliferation, and induces cell apoptosis in both cell lines. SU9516 kills leukemic cells through inhibition of RNA Pol II CTD phosphorylation, oxidative damage and transcriptional down-regulation of Mcl-1. In human T-cell leukemia Jurkat cells, SU9516 significantly enhances sensitivity to methotrexate. In addition, SU9516 also suppresses Aurora-A centrosomal localization and consequent centrosome amplification. SU9516是一种3位取代的吲哚酮类CDK抑制剂，对CDK2，CDK1，和CDK4的IC50分别为22 nM，40 nM，和200 nM。

Target	Value
CDK2 ()	22 nM
CDK1	40 nM
CDK4	200 nM

在RKO和SW480细胞中，SU9516减小cdk2特定的视网膜细胞瘤蛋白pRB磷酸化作用， 增加胱天蛋白酶-3的活化作用，并改变细胞周期。SU9516也会抑制细胞系中细胞增殖，并诱导细胞凋亡。 SU9516通过抑制RNA Pol II CTD磷酸化，氧化性损伤以及Mcl-1的转录下调从而杀死白血病细胞。在人T细胞白血病Jurkat细胞，SU9516显著增强对甲氨蝶呤的敏感性。此外，SU9516也会抑制Aurora-A中心体定位和随后的中心体扩增。