Anticancer potentiating effect and downregulation of PD‐L1 expression: Study on the 2‐[( p ‐fluorophenyl)amino]‐ 6‐substituted‐9 H ‐purine analogues as novel CHK1 inhibitors

Abstract In this study, a series of 2‐[ p ‐fluorophenyl]‐6‐substituted‐9 H ‐purine analogues were designed and synthesized as CHK1 inhibitors, among which compound b22 was the most potent. b22 exhibited nearly no antiproliferative activity toward HT29 cells and displayed a significant antitumor potentiating effect on HT29 cells when treated in combination with gemcitabine (Gem). A time‐dependent assay found that treatment with Gem for 8 h before adding b22 achieved the optimal effect. Furthermore, the immunofluorescence and qPCR results demonstrated that b22 can remarkably reverse the upregulation of PD‐L1 induced by Gem, which suggested dual effects of b22 in antitumor potentiation and antitumor immunity.