GGTI298 Trifluoroacetate (GGTI 298 TFA salt) is a geranylgeranyltransferase I inhibitor with ability to arrest human tumor cells in the G1 phase of the cell cycle and induce apoptosis.

Ha-Ras:>20 μM., Rap1A:3 μM

Geranylgeranyltransferase I 抑制剂GGTI-298已被证实能够使人类肿瘤细胞在细胞周期的G1阶段停滞并诱导凋亡。使用GGTI-298处理人类肺癌细胞系Calu-1会导致视网膜母细胞瘤蛋白磷酸化的抑制，这是G1/S过渡的关键步骤。在GGTI-298处理的Calu-1细胞中，两种G1/S周期依赖性激酶，CDK2和CDK4的激酶活性被抑制。GGTI-298对CDK2, CDK4, CDK6, 细胞周期蛋白D1和E的表达水平影响不大，但会降低细胞周期蛋白A的水平。GGTI-298提高了细胞周期依赖性激酶抑制剂p21和p15的水平，对p27和p16的影响较小。GGTI-298促进p21和p27与CDK2的结合，同时减少它们与CDK6的结合。其处理增强了p15与CDK4的结合，这与p27的结合减少相平行。用GGTI-298预处理成纤维细胞，可以阻断PDGF和表皮生长因子依赖的酪氨酸激酶受体的酪氨酸磷酸化。GGTI-298对成纤维细胞、上皮细胞和平滑肌细胞具有抗增殖效果，这种细胞生长抑制似乎是通过G1阶段停滞介导的[1]。

GGTI-298 在裸鼠中抑制了肿瘤生长[1]。

Cells were treated with GGTI-298 (15 μM) for 48 h, harvested, and lysed in HEPES lysis buffer. Proteins were then resolved by 12.5% or 7% SDS-PAGE gel and immunoblotted with antibodies. The ECL blotting system was used for detection of positive antibody reactions.(Only for Reference)