Chk2
Checkpoint kinase Chk2 (CHEK2) is a serine/threonine kinase and key DNA damage response component that coordinates checkpoint activation, DNA repair, apoptosis, senescence, or damage tolerance after genotoxic stress[1]. Mechanistically, ATM-mediated Thr68 phosphorylation triggers CHK2 dimerization through phospho-Thr68-FHA interactions, followed by activation-loop autophosphorylation and kinase activation[2]. Activated CHK2 connects DNA damage signaling to p53 stabilization, BRCA1 phosphorylation, and cell-cycle control, therefore supporting genome integrity research in cancer models[3][4]. In disease contexts, CHK2 functions as a tumor-suppressive kinase linked to cancer susceptibility, while experimental data also show context-dependent roles in DNA damage-induced apoptosis and checkpoint arrest[5][6]. Compared with Chk1, CHK2 is structurally distinct and is activated mainly by DNA damage, whereas Chk1 has a broader role in S-phase and G2 checkpoint control[6]. For experimental applications, the selective CHK2 inhibitor CCT241533 blocks CHK2 activity in tumor cell lines after DNA damage and potentiates cytotoxicity of PARP inhibitors, supporting pathway-dissection studies rather than unsupported monotherapy claims[7].- CHK2 links ATM-driven DNA damage signaling to p53, BRCA1, apoptosis, and checkpoint control. - CHK2 differs from Chk1 in activation pattern, checkpoint dependence, and experimental inhibitor utility.
References:
- [1]. Zannini L, et al. CHK2 kinase in the DNA damage response and beyond. J Mol Cell Biol. 2014 Dec;6(6):442-57. [Content Brief]
- [2]. Cai Z, et al. Structure and activation mechanism of the CHK2 DNA damage checkpoint kinase. Mol Cell. 2009 Sep 24;35(6):818-29. [Content Brief]
- [3]. Hirao A, et al. DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science. 2000 Mar 10;287(5459):1824-7. [Content Brief]
- [4]. Lee JS, et al. hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response. Nature. 2000 Mar 9;404(6774):201-4. [Content Brief]
- [5]. Antoni L, et al. CHK2 kinase: cancer susceptibility and cancer therapy - two sides of the same coin? Nat Rev Cancer. 2007 Dec;7(12):925-36. [Content Brief]
- [6]. Bucher N, et al. G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer. Br J Cancer. 2008 Feb 12;98(3):523-8. [Content Brief]
- [7]. Anderson VE, et al. CCT241533 is a potent and selective inhibitor of CHK2 that potentiates the cytotoxicity of PARP inhibitors. Cancer Res. 2011 Jan 15;71(2):463-72. [Content Brief]
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Chk2 Related Products (42)
Related Products (42)
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Recombinant Proteins (4)
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Antibodies (2)
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Elrelesertib (Standard)
0 ImagesCat. No.: HY-109566RCAS No.: 2089288-03-7Synonyms: AZD1390 (Standard)Elrelesertib (Standard) (AZD1390 (Standard)) is the analytical standard of Elrelesertib (AZD1390) (HY-109566). This product is intended for research and analytical applications. Elrelesertib (AZD1390) is an orally active, brain-penetrant ATM kinase inhibitor with IC50 values of 0.78 nM. Elrelesertib blocks ATM-dependent DNA damage response, inhibits ATM autophosphorylation and downstream Chk2, Rad50 phosphorylation, and accumulates at DNA breaks. Elrelesertib acts as a radiosensitizer, induces apoptosis, genomic instability, G2-M cell cycle arrest, ROS elevation, and mitochondrial membrane potential alteration. Elrelesertib has low efflux liability against P-gp and BCRP. Elrelesertib can be used for the research of central nervous system malignancies, glioblastoma multiforme, glioma, lung cancer brain metastases, and breast cancer.
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CHK-IN-1
0 ImagesCat. No.: HY-U00345CAS No.: 1278405-51-8
