2021年1月28日 · A recent study shows that CHK1 is essential for controlling hematopoietic stem and progenitor cell (HSPC) development and expansion; conditional deletion of CHK1 in definitive hematopoietic stem cells caused failure of fetal hematopoiesis and impaired adult hematopoiesis, while, chemical inhibition of CHK1 killed both murine and human HSPCs [26].

2024年6月1日 · Here, we review the latest research progress on the functions of CHK1, classification and development status of CHK1i and its combination regimen and potential predictive biomarkers to provide new ideas for promoting the development of CHK1i.

In 1997, Chk1 orthologs from fruit fly (drosophila ‘grapes’), human and mouse (CHK1) were identified 12–15. In this review, we will summarize how Chk1 is regulated with a particular focus on human Chk1.

In this review, we discuss Chk1 regulation, its role in DDR and unperturbed cell cycle, and the possibility of targeting Chk1 for cancer therapy. The cell cycle consists of a series of highly ordered, sequential phases that lead to cell division [5].

ATR/CHK1 inhibitors have been developed and are currently used either as single agents or paired with radiotherapy or a variety of genotoxic chemotherapies in preclinical and clinical studies. Here, we review the status of the development of ATR and CHK1 inhibitors.

In addition, suppressing DNA damage and replication checkpoint responses by inhibiting Chk1 can enhance tumor cell killing by diverse genotoxic agents. Here, we review current understanding of the organization and functions of the ATM-Chk2 and ATR-Chk1 pathways and the prospects for targeting DNA damage signaling processes for therapeutic purposes.

This review is intended to provide information on the current progress of CHK1 inhibitors in pre-clinical and clinical development and will focus on mechanisms of single-agent activity and potential strategies for patient tailoring and combinations with non-genotoxic agents.

Areas covered: This review discusses the history of, and translational use of CHK1 inhibitors; the latest generation of CHK1 inhibitors to enter clinic development are also examined.

2017年11月22日 · Checkpoint kinase 1 (CHK1) is critical for intrinsic cell cycle control and coordination of cell cycle progression in response to DNA damage. Despite its essential function, CHK1...

CHK1 is a 54.4 kDa serine/threonine-specific protein kinase that plays, with CHK2, a pivotal role in maintaining DNA integrity. CHK1 is a substrate of ATR and its activation is therefore particularly important in the response to SSB sensing.