chk1 inhibitor mk8776  (MedChemExpress)

Journal: Journal of Experimental & Clinical Cancer Research : CR

Article Title: hnRNPA1-SF3B3 interaction drives radioresistance in oral squamous cell carcinoma by modulating MARF1 alternative splicing isoforms

doi: 10.1186/s13046-026-03697-4

Figure Lengend Snippet: hnRNPA1 promoted DNA repair through MARF1-L–mediated PPP1R10 mRNA degradation and activation of Chk1 phosphorylation. A - B Homologous recombination (HR) repair efficiency in OSCC cells transduced with scramble, sh-hnRNPA1, sh-hnRNPA1 + MARF1-L or sh-hnRNPA1 + MARF1-S constructs; ( C ) Representative immunofluorescence images and ( D )quantification assessing RAD51 foci formation in the indicated OSCC cell groups at 12 h after 6 Gy IR. Scale bar, 20 μm; ( E ) Enrichment analysis of Gene Ontology terms for downregulated differential genes (MARF1-L vs. MARF1-S groups), CC: Cellular Component, MF: Molecular Function. F Heatmap of qPCR analysis of PPP1R10 and PPP1R3G mRNA levels in control, MARF1-L, and MARF1-S OSCC cells. G Western blot analysis of PPP1R10, Chk1, p-Chk1 (S345) protein levels in the indicated OSCC cells at 12 h post-IR; ( H ) Schematic model illustrating how hnRNPA1 facilitated radioresistance by promoting MARF1-L–dependent degradation of PPP1R10 mRNA and subsequent activation of CHK1 signaling Statistical significance was determined by two-tailed Student’s t-test or two-way ANOVA followed by Tukey’s post hoc test, as appropriate. * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001; ns, not significant

Article Snippet: OSCC cells were treated with the following pharmacological inhibitors: 25 nM of the PP1 inhibitor Okadaic acid (MCE, Cat. No. HY-N6785) for 24 h; 2 μM of the ATR inhibitor AZD6738 (MCE, Cat. No. AZD6738) for 24 h; and 1 μM of the CHK1 inhibitor MK8776 (MCE, Cat. No. MK8776) for 24 h.

Techniques: Activation Assay, Phospho-proteomics, Homologous Recombination, Transduction, Construct, Immunofluorescence, Control, Western Blot, Two Tailed Test

Journal: Nature Communications

Article Title: Selective targeting of genome amplifications and repeat elements by CRISPR-Cas9 nickases to promote cancer cell death

doi: 10.1038/s41467-025-60160-2

Figure Lengend Snippet: A , B SK-N-BE(2)C, NGP, and SH-SY5Y cells expressing ( A ) LINE-1 or ( B ) MYCN targeting sgRNA were treated with Cas9 D10A -mRNA at increasing doses in the absence or presence of a CHK1 inhibitor, MK8776 (500 nM). Co-treatment with CHK1i potentiated Cas9 D10A -mediated cell-killing across cell lines at 3 days post-treatment ( n = 3 biological replicates). Data were analyzed by multiple unpaired t -tests (two-tailed); ns, P > 0.05; * P ≤ 0.05; ** P ≤ 0.01; *** P ≤ 0.001; **** P ≤ 0.0001. C Average MYCN and ALK genome copy number in IMR-32 cells determined by qPCR ( n = 4 biological replicates). Data are presented normalized to HFF cells as a baseline control where for each box plot the horizontal line represents the median, the top and bottom of the box represent the upper and lower quartiles, respectively, and the top and bottom whiskers represent the maximum and minimum values, respectively. D Targeting of LINE-1 , MYCN , ALK , or MYCN and ALK in IMR-32 cells (2 × 105) with Cas9 D10A demonstrates a dose-dependent cytotoxic effect. Multiplex targeting of MYCN and ALK increases Cas9 D10A -mediated cell-killing relative to targeting MYCN or ALK individually ( n = 3 biological replicates). Data were analyzed using a two-way ANOVA with a Tukey’s multiple comparison test; ns, P > 0.05; * P ≤ 0.05; ** P ≤ 0.01; *** P ≤ 0.001; **** P ≤ 0.0001. E No additional cellular toxicity is observed for multiplex targeting of an amplified ( MYCN or ALK ) locus with a non-amplified ( AAVS1 ) locus in IMR-32 cells with Cas9 D10A -mRNA (15 nM; n = 3 biological replicates). Data were analyzed by multiple unpaired t -tests (two-tailed); ns, P > 0.05; * P ≤ 0.05; ** P ≤ 0.01; *** P ≤ 0.001; **** P ≤ 0.0001. F Multiplex targeting of non-amplified loci in SH-SY5Y cells with Cas9 D10A -mRNA (30 nM) resulted in similar rates of cell viability to targeting individual loci. Cells were assessed for changes in cell viability at 3 days post-treatment with Cas9 D10A -mRNA ( n = 3). Data in panels ( A , B , and E , F ) is presented as mean ± s.d. and normalized relative to viability of cells expressing AAVS1 targeting sgRNA treated with Cas9 D10A . Source data are provided as a Source Data file.

Article Snippet: Cell proliferation was monitored at 1-, 2-, and 3 days post-treatment with Cas9 nickase mRNA or by QIBC using the Celigo Image Cytometer (Nexcelcom Bioscience, USA) to measure the cell population following staining cell with Hoecsht 33342 (1 μg/mL; Invitrogen, #H1399) at 37 °C for 30 min. Where applicable, cells were supplemented with various reagents: in the presence of MK8776 (MedChemExpress, #HY-15532), rucaparib (MedChemExpress, #HY-10617A), PDD00017273 (MedChemExpress, # HY-108360), berzosertib (Selleck, #S7102), calpastatin (Millipore Sigma, #208902), alisertib (MedChemExpress, #HY-10971), etoposide (MedChemExpress, #HY-13629R), or topotecan (MedChemExpress, #HY-13768A) at concentrations ≤IC50 to prevent confounding toxicity.

Techniques: Expressing, Two Tailed Test, Control, Multiplex Assay, Comparison, Amplification

Journal: Genes, chromosomes & cancer

Article Title: Upregulation of the ATR-CHEK1 Pathway in Oral Squamous Cell Carcinomas

doi: 10.1002/gcc.22115

Figure Lengend Snippet: TABLE 1

Article Snippet: The Merck CHEK1 inhibitor (MK8776/SCH900776) has been shown to be effective in combination with cytarabine in refractory AML ( Karp et al., 2012 ; Schenk et al., 2012 ).

Techniques: