GNE-783 是一款高选择性 CHK1 抑制剂,可有效增强吉西他滨的抗肿瘤效果。GNE-783在 DNA 损伤发生后,通过使 S 期与 G2 期细胞周期检查点失活,从而提升抗代谢类 DNA 损伤药物的治疗作用。GNE-783 对不同肿瘤的化疗增敏具有选择性,例如仅在黑色素瘤细胞系中能增强替莫唑胺的抗肿瘤活性。
PD-321852 is a small-molecule Chk1 inhibitor, which potentiates gemcitabine-induced clonogenic death in a panel of pancreatic cancer cell lines and evaluated the relationship between endpoints associated with Chk1 inhibition and chemosensitization. Gemcitabine chemosensitization by minimally toxic concentrations of PD-321852 ranged from minimal (<3-fold change in survival) in Panc1 cells to >30-fold in MiaPaCa2 cells. PD-321852 inhibited Chk1 in all cell lines as evidenced by stabilization of Cdc25A; in combination with gemcitabine, a synergistic loss of Chk1 protein was observed in the more sensitized cell lines.
INO-1001 methanesulfonate is an isoindolinone derivative and potent inhibitor of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) with chemosensitization and radiosensitization properties.