PF-477736 is a potent and selective inhibitor of checkpoint kinase 1 (Chk1), a key protein involved in the DNA damage response pathway. Its primary application lies in cancer research, particularly in enhancing the effectiveness of DNA-damaging chemotherapeutic agents. By inhibiting Chk1, PF-477736 prevents cancer cells from arresting the cell cycle to repair DNA damage, thereby promoting cell death when used in combination with agents like gemcitabine, cisplatin, or radiation.

It has been widely used in preclinical studies to investigate synthetic lethality and to overcome chemoresistance in tumor cells, especially in cancers with p53 deficiencies where the G1 checkpoint is impaired and cells rely more heavily on Chk1-mediated S and G2 checkpoints. This makes PF-477736 a valuable tool in developing targeted combination therapies aimed at increasing tumor sensitivity while sparing normal tissues.

Due to its role in abrogating cell cycle arrest, it is also employed in mechanistic studies to dissect DNA damage signaling pathways and to validate Chk1 as a therapeutic target in oncology.