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 (48)
Related Products (48)
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Recombinant Proteins (4)
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Antibodies (2)
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Americanin A
0 ImagesCat. No.: HY-N18301CAS No.: 69506-79-2Americanin A is a Neolignan. Americanin A can be isolated from the seeds of Phytolacca americana. Americanin A activates ATM and ATR, initiating the subsequent signal transduction cascades that include Chk1, Chk2, and tumor suppressor p53. Americanin A targets selectively Skp2 for degradation and thereby stabilizes p27. Americanin A suppresses the activity of Cyclin B1 and its partner cdc2 to prevent entry into Mitosis. Americanin A induces Apoptosis by producing excessive ROS. Americanin A has anti-cancer activity against colorectal cancer.
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PV1162
0 ImagesCat. No.: HY-164523CAS No.: 1093793-11-3PV1162 is a selective Chk2 inhibitor with an IC50 of 0.29 nM. PV1162 inhibits ATP binding to Chk2 by targeting the gatekeeper-dependent hydrophobic pocket, which is specific to Chk2 and located behind the ATP-binding site (adenine-binding region), thereby inhibiting the phosphorylation activity of Chk2. PV1162 holds potential application value in the field of cancer therapy.
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Benfluron hydrochloride
0 ImagesCat. No.: HY-106419ACAS No.: 80427-58-3Synonyms: Benflurone hydrochlorideBenfluron hydrochloride is an Apoptosis inducer and inhibitor of the HIV-1 Rev-RRE complex, with an IC50 of 5.0 μM against the HIV-1 Rev-RRE complex. Benfluron hydrochloride induces p53 activation, and triggers phosphorylation of Chk1 at serine 345, Chk2 at threonine 68, as well as ERK1/2 at threonine 202 and tyrosine 204. Benfluron hydrochloride activates Caspase 8, Caspase 9 and Caspase 3/7, inhibits HIV-1 viral transcription, and acts as a substrate for 11β-HSD 1 and cytosolic carbonyl reductase. Benfluron hydrochloride can be used in research related to leukemia and HIV-1 infection.
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(E/Z)-PV1162
0 ImagesCat. No.: HY-164523ACAS No.: 1346559-65-6
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Prexasertib lactate
0 ImagesCat. No.: HY-18174HCAS No.: 2781996-46-9Synonyms: LY2606368 lactatePrexasertib lactate (LY2606368 lactate) is the lactate form of Prexasertib (HY-18174). Prexasertib lactate is a selective, ATP-competitive second-generation checkpoint kinase 1 (CHK1) inhibitor with a Ki of 0.9 nM and an IC50 of <1 nM. Prexasertib lactate inhibits CHK2 (IC50=8 nM) and RSK1 (IC50=9 nM). Prexasertib lactate causes double-stranded DNA breakage and replication catastrophe resulting in apoptosis. Prexasertib lactate shows potent anti-tumor activity.
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CX-5461 (Standard)
0 ImagesCX-5461 (Standard) is the analytical standard of CX-5461 (HY-13323). This product is intended for research and analytical applications. CX-5461 is a selective, orally active RNA polymerase I inhibitor. CX-5461 disrupts the formation of the SL1-rDNA complex, thereby blocking the transcription initiation of ribosomal RNA without altering the activity of RNA polymerase II, DNA replication, or protein translation processes. CX-5461 upregulates the expression of p21, MDM2, Sestrin1/2, and phosphorylated AMPKα, and reduces the level of phosphorylated Akt. CX-5461 induces G2/G2/M cell cycle arrest, Autophagy, Apoptosis, and cellular senescence, and activates CHK1, CHK2, and RPA. CX-5461 can be used in research related to osteosarcoma, cervical cancer, hematologic malignancies, high-grade serous ovarian cancer, and solid tumors.
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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
