Chk1
Chk1 (checkpoint kinase 1) mediates the DNA damage response and normal cell-cycle regulation through checkpoint activation, cell-cycle arrest, DNA repair, and cell death control[1]. Mechanistically, Chk1 functions as a key transducer in genome-integrity checkpoints, especially within ATR-linked responses to stalled replication and genotoxic stress[2][3]. In cancer research, this role makes Chk1 relevant to replication stress, BRCA wild-type ovarian cancer models, and studies combining checkpoint inhibition with DNA-damaging therapy[4][5]. Compared with Chk2, Chk1 shows distinct activation biology and experimentally separable checkpoint functions, while Chk1-S acts as an endogenous splice-variant inhibitor that regulates Chk1-dependent checkpoints[2][6]. For experimental applications, Chk1 inhibitors such as prexasertib/LY2606368 induce replication catastrophe and have been tested in tumor models and recurrent high-grade serous ovarian cancer[7][8].
References:
- [1]. Patil M, et al. Checkpoint kinase 1 in DNA damage response and cell cycle regulation. Cell Mol Life Sci. 2013 Nov;70(21):4009-21. [Content Brief]
- [2]. Bartek J, et al. Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell. 2003 May;3(5):421-9. [Content Brief]
- [3]. Dai Y, et al. New insights into checkpoint kinase 1 in the DNA damage response signaling network. Clin Cancer Res. 2010 Jan 15;16(2):376-83. [Content Brief]
- [4]. Rabezanahary H, et al. Live virus neutralizing antibodies against pre and post Omicron strains in food and retail workers in Québec, Canada. Heliyon. 2024 May 21;10(10):e31026. [Content Brief]
- [5]. Nair J, et al. Resistance to the CHK1 inhibitor prexasertib involves functionally distinct CHK1 activities in BRCA wild-type ovarian cancer. Oncogene. 2020 Aug;39(33):5520-5535. [Content Brief]
- [6]. Pabla N, et al. Checkpoint kinase 1 (Chk1)-short is a splice variant and endogenous inhibitor of Chk1 that regulates cell cycle and DNA damage checkpoints. Proc Natl Acad Sci U S A. 2012 Jan 3;109(1):197-202. [Content Brief]
- [7]. King C, et al. LY2606368 Causes Replication Catastrophe and Antitumor Effects through CHK1-Dependent Mechanisms. Mol Cancer Ther. 2015 Sep;14(9):2004-13. [Content Brief]
- [8]. Lee JM, et al. Prexasertib, a cell cycle checkpoint kinase 1 and 2 inhibitor, in BRCA wild-type recurrent high-grade serous ovarian cancer: a first-in-class proof-of-concept phase 2 study. Lancet Oncol. 2018 Feb;19(2):207-215. [Content Brief]
All Product Categories
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Chk1 Related Products (62)
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Recombinant Proteins (2)
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Antibodies (3)
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Prexasertib
0 ImagesSynonyms: LY2606368Prexasertib (LY2606368) 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 inhibits CHK2 (IC50=8 nM) and RSK1 (IC50=9 nM). Prexasertib causes double-stranded DNA breakage and replication catastrophe resulting in apoptosis. Prexasertib shows potent anti-tumor activity.
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AZD-7762
0 ImagesAZD-7762 is a potent ATP-competitive checkpoint kinase (Chk) inhibitor in with an IC50 of 5 nM for Chk1.
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BEN-28010
0 ImagesCat. No.: HY-186085CAS No.: 3033961-38-2BEN-28010 is a selective, orally active, blood-brain barrier permeable CHK1 inhibitor with an IC50 of 4.0 nM. BEN-28010 functions as a radiosensitizer, exhibits antitumor efficacy in GBM models. BEN-28010 can be used for the research of glioblastoma.
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4"-Isovalerylspiramycin I
0 ImagesCat. No.: HY-N15249CAS No.: 267662-22-6Synonyms: Isovalerylspiramycin I; Shengjimycin E4"-Isovalerylspiramycin I (Isovalerylspiramycin I) is a topoisomerase 1 (TOP1) inhibitor and an antitumor agent. 4"-Isovalerylspiramycin I directly binds to TOP1, suppresses DNA replication, and induces DNA damage. 4"-Isovalerylspiramycin I downregulates phosphorylated CHEK1 and the ATR/CHEK1 DNA damage repair pathway, blocks DNA repair, and augments DNA damage. 4"-Isovalerylspiramycin I suppresses proliferation, migration, and invasion of osteosarcoma cells. 4"-Isovalerylspiramycin I induces apoptosis and cell cycle arrest in osteosarcoma cells. 4"-Isovalerylspiramycin I exerts antibacterial activity against methicillin-resistant Staphylococcus aureus. 4"-Isovalerylspiramycin I can be used for the research of osteosarcoma, upper respiratory bacterial infections, and methicillin-resistant Staphylococcus aureus infection.
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ART0380
0 ImagesART0380 is a potent, selective and orally active ATR kinase inhibitor. ART0380 potently inhibits human ATR-ATRIP complex with an IC50 of 51.7 nM. ART0380 binds the ATP pocket of the ATR-ATRIP complex, blocks ATR-dependent Chk1 serine 345 phosphorylation, and induces cell cycle disorder and DNA damage. ART0380 demonstrates potent and selective antitumor activity in preclinical models with varying types of ataxia-telangiectasia mutated (ATM) gene aberrancy. ART0380 can be used for the research of cancer, such as colorectal cancer and prostate cancer.
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PF 477736
0 ImagesSynonyms: PF 00477736PF 477736 (PF 00477736) is a potent, selective and ATP-competitive inhibitor of Chk1, with a Ki of 0.49 nM, it is also a Chk2 inhibitor, with a Ki of 47 nM. PF 477736 shows <100-fold selectivity for Chk1 over VEGFR2, Fms, Yes, Aurora-A, FGFR3, Flt3, and Ret (IC50=8 (Ki), 10, 14, 23, 23, 25, and 39 nM, respectively). PF 477736 can enhance Gemcitabine antitumor activity in vitro and in vivo.
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Prexasertib dihydrochloride
0 ImagesSynonyms: LY2606368 dihydrochloridePrexasertib dihydrochloride (LY2606368 dihydrochloride) 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 dihydrochloride inhibits CHK2 (IC50=8 nM) and RSK1 (IC50=9 nM). Prexasertib dihydrochloride causes double-stranded DNA breakage and replication catastrophe resulting in apoptosis. Prexasertib dihydrochloride shows potent anti-tumor activity.
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PD 407824
0 ImagesPD 407824 is a checkpoint kinase Chk1 and WEE1 inhibitor with IC50s of 47 and 97 nM, respectively. PD 407824 is a chemical BMP sensitizer and increases the sensitivity of cells to sub-threshold amounts of BMP4.
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SB-218078
0 ImagesSB-218078 is a potent, selective, ATP-competitive and cell-permeable checkpoint kinase 1 (Chk1) inhibitor that inhibits Chk1 phosphorylation of cdc25C with an IC50 of 15 nM. SB-218078 is less potently inhibits Cdc2 (IC50 of 250 nM) and PKC (IC50 of 1000 nM). SB-218078 causes apoptosis by DNA damage and cell cycle arrest.
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Prexasertib dimesylate
0 ImagesSynonyms: LY2606368 dimesylatePrexasertib dimesylate (LY2606368 dimesylate) 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 dimesylate inhibits CHK2 (IC50=8 nM) and RSK1 (IC50=9 nM). Prexasertib dimesylate causes double-stranded DNA breakage and replication catastrophe resulting in apoptosis. Prexasertib dimesylate shows potent anti-tumor activity.
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SAR-020106
0 ImagesSAR-020106 is an ATP-competitive, potent, and selective CHK1 inhibitor with an IC50 of 13.3 nM for human CHK1. SAR-020106 shows excellent selectivity over CHK2. SAR-020106 significantly enhances the cell killing of Gemcitabine and SN38 by 3- to 29-fold in several colon tumor lines and in a p53-dependent fashion. SAR-020106 can enhance antitumor activity with selected anticancer agents.
