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    GENE:

    CHEK1 (Checkpoint kinase 1)

    i
    Other names: CHEK1, CHK1, Checkpoint kinase 1
    3d
    Targeting IP6 signaling to destabilize homologous recombination proteins to overcome PARP inhibitor resistance. (PubMed, Nat Commun)
    These findings reveal a Cul4A-WDR5-dependent proteolysis pathway regulating HR protein stability via phosphatidyl inositol signaling. This mechanism offers a promising therapeutic strategy for overcoming PARPi resistance and improving combinatorial cancer treatment strategies.
    Journal
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    RAD51 (RAD51 Homolog A) • CUL4A (Cullin 4A) • CHEK1 (Checkpoint kinase 1) • WDR5 (WD Repeat Domain 5) • PIP5K1C (Phosphatidylinositol-4-Phosphate 5-Kinase Type 1 Gamma)
    7d
    New Schiff Base Derivative Triazines: Their Synthesis, Molecular Docking Studies, and Anticancer Activities in Human Lung Cancer Cells. (PubMed, Chem Biol Drug Des)
    The drug-likeness potential of the TrzSchf derivatives was evaluated based on Lipinski's Rule of Five parameters. Overall, both experimental and computational results suggest that TrzSchf 1-3 are promising lead candidates for further investigation in lung cancer therapy.
    Journal • IO biomarker
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    BCL2 (B-cell CLL/lymphoma 2) • CHEK1 (Checkpoint kinase 1) • CASP3 (Caspase 3) • CD40 (CD40 Molecule)
    7d
    Next-Generation Therapeutic Targets in Triple-Negative Breast Cancer. (PubMed, Eur J Breast Health)
    Metabolic reprogramming (glycolysis, fatty-acid oxidation/synthesis, and amino-acid use) intersects with therapy resistance and may provide complementary combination opportunities. In this study, we synthesize recent advances in actionable TNBC pathways, summarize key preclinical and clinical evidence, and propose a pragmatic framework for biomarker-led combinations that integrate DNA repair, cell-cycle, metabolic, and immune vulnerabilities.
    Journal • BRCA Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • AR (Androgen receptor) • HRD (Homologous Recombination Deficiency) • FGFR (Fibroblast Growth Factor Receptor) • ATR (Ataxia telangiectasia and Rad3-related protein) • CHEK1 (Checkpoint kinase 1)
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    BRCA2 mutation • BRCA1 mutation
    11d
    Crude Venom from Sea Anemone Macrodactyla doreensis Suppresses Glioblastoma via the p53 Pathway. (PubMed, Mar Drugs)
    Combined with AlphaFold2-based structural modeling and molecular docking, these analyses further elucidated the potential molecular mechanisms underlying their interactions with key targets, such as MD-381 with RRM2, MD-322 with CDK2, and MD-429 with CHEK1. Collectively, these findings highlight the therapeutic potential of M. doreensis crude venom and lay a foundation for the subsequent isolation of novel peptides and their further development in glioblastoma treatment.
    Journal
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    CHEK1 (Checkpoint kinase 1) • CDK2 (Cyclin-dependent kinase 2) • EGF (Epidermal growth factor) • RRM2 (Ribonucleotide Reductase Regulatory Subunit M2) • ANXA5 (Annexin A5)
    12d
    PRMT5 inhibition triggers functional ATM deficiency and sensitizes pancreatic cancer to CHK1 blockade. (PubMed, Front Cell Dev Biol)
    Treated tumors showed reduced ATM and Ki67 with elevated γH2A.X. Together, these findings identify PRMT5 inhibition as a trigger of reduced ATM function that exposes a therapeutically actionable vulnerability to CHK1 inhibition, offering a rational, mechanistically-based combination strategy for this dismal disease.
    Journal
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    ATM (ATM serine/threonine kinase) • CHEK1 (Checkpoint kinase 1) • CASP3 (Caspase 3) • CASP7 (Caspase 7) • ANXA5 (Annexin A5)
    13d
    BMAL1 silencing as a promising chemosensitizing strategy for triple-negative breast cancer. (PubMed, Acta Pharmacol Sin)
    This synergistically increases the sensitivity of TNBC cells to etoposide. Our findings reveal BMAL1 as a promising therapeutic target and support the potential of silencing BMAL1 with siRNA as a neoadjuvant strategy in combination with chemotherapeutic agents for the treatment of TNBC.
    Journal
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    CHEK1 (Checkpoint kinase 1) • ARNTL (Aryl Hydrocarbon Receptor Nuclear Translocator Like)
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    etoposide IV
    14d
    Elucidating the potential carcinogenic molecular mechanisms of parabens in head and neck squamous cell carcinoma through network toxicology and molecular docking. (PubMed, PLoS One)
    Parabens may promote HNSCC progression by disrupting cell cycle regulation and immune responses via direct interactions with key hub genes. These findings provide a novel mechanistic basis for the carcinogenic potential of parabens in HNSCC and underscore the need for further experimental and epidemiological validation.
    Journal
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    CD8 (cluster of differentiation 8) • CDK4 (Cyclin-dependent kinase 4) • TYMS (Thymidylate Synthetase) • AURKA (Aurora kinase A) • PLK1 (Polo Like Kinase 1) • CHEK1 (Checkpoint kinase 1) • CCNA2 (Cyclin A2) • CDK2 (Cyclin-dependent kinase 2) • CCNB2 (Cyclin B2) • CDK1 (Cyclin-dependent kinase 1) • CCNA1 (Cyclin A1) • CCNB1 (Cyclin B1) • CDC25A (Cell Division Cycle 25A) • GNRP (Ras-Specific Guanine Nucleotide-Releasing Factor 1)
    14d
    Radix Aconiti Lateralis Preparata and Coptidis Rhizoma mitigate the course of acute myeloid leukemia. (PubMed, Am J Transl Res)
    As traditional Chinese medicine, RALP and CR effectively alleviate AML tumor burden, and their combination demonstrates synergistic effects.
    Journal
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    ER (Estrogen receptor) • IL6 (Interleukin 6) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • CHEK1 (Checkpoint kinase 1) • CASP3 (Caspase 3) • PTGS2 (Prostaglandin-Endoperoxide Synthase 2) • CALM1 (Calmodulin 1) • PACERR (PTGS2 Antisense NFKB1 Complex-Mediated Expression Regulator RNA)
    14d
    A Phase I/II Study of Sacituzumab Govitecan Plus Berzosertib in Small Cell Lung Cancer, Extra-Pulmonary Small Cell Neuroendocrine Cancer and Homologous Recombination-Deficient Cancers Resistant to PARP Inhibitors (clinicaltrials.gov)
    P1/2, N=120, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2027 --> Mar 2029 | Trial primary completion date: Mar 2026 --> Mar 2028
    Trial completion date • Trial primary completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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    BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation
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    berzosertib (M6620) • Trodelvy (sacituzumab govitecan-hziy)
    19d
    Microenvironmental acidosis drives PARP- and ATM inhibitor resistance in p53 deficient pancreatic cancer. (PubMed, iScience)
    Whereas p53 KO organoids are sensitive to the combined inhibition of ATM and PARP, acid adaptation partially rescues this phenotype, increasing treatment resistance in a manner partially restored by the combined inhibition of pH-regulatory transporters. We conclude that p53 loss rewires acid-base homeostasis and that microenvironment acidity limits treatment response in p53-deficient PDAC, possibly by increasing cancer cell pH homeostasis capacity.
    Journal • PARP Biomarker
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    TP53 (Tumor protein P53) • ATR (Ataxia telangiectasia and Rad3-related protein) • CHEK1 (Checkpoint kinase 1)
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    TP53 mutation
    19d
    Comprehensive genomic analysis of non-BRCA familial breast cancer in an Arab population. (PubMed, NPJ Breast Cancer)
    PRS assessment identified four PRSs with good discriminatory power (AUC > 0.690), with PGS003738 showing the highest performance (AUC = 0.702, top decile OR = 3.57). These findings highlight the need for population-specific genetic studies to improve breast cancer risk stratification in Arab populations.
    Journal • BRCA Biomarker
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • PALB2 (Partner and localizer of BRCA2) • BRCA (Breast cancer early onset) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1)
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    BRCA2 mutation • BRCA1 mutation
    21d
    Discovery of dihydrospiro[cyclopropane-1,7'-pyrrolo[3,4-d]pyrimidine] derivatives as novel ATR inhibitors. (PubMed, RSC Med Chem)
    Pairwise drug combinational antiproliferative assays revealed that 10h and niraparib synergistically enhanced antiproliferative effects against Granta-519. These results suggested that 10h holds promise for further development as a lead compound for the design of ATR kinase-targeted therapies.
    Journal
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    CHEK1 (Checkpoint kinase 1)
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    Zejula (niraparib)