cdk4 6 inhibitors  (MedChemExpress)

Journal: Frontiers in Pharmacology

Article Title: Genome-wide CRISPR screen identified NEK6 as a determinant of sensitivity to CDK4/6 inhibitor in endometrial cancer

doi: 10.3389/fphar.2025.1725886

Figure Lengend Snippet: NEK6 knockout enhanced the efficiency of CDK4/6 inhibitor-induced DNA damage repair and apoptosis. (A) DNA damage detected by comet assay in HEC-1A cells (siNC or si-NEK6) treated with indicated concentration of palbociclib. Scale bar, 50 μm. Quantification of DNA in the tail from three independent experiments is shown as mean ± s.d. (B) Immunofluorescence staining of γ-H2AX in sh-NC and sh-NEK6 HEC-1A and Ishikawa cells treated with or without palbociclib. Scale bar = 10 μm. (C) Western blot analysis of phosphorylated H2AX and RAD51 in HEC-1A and ishikawa endometrial cancer cells treated as indicated. (D) Knockdown of NEK6 induced apoptosis significantly upon palbociclib treatment in HEC-1A evaluated by flow cytometry analysis. Data were presented as the mean ± s.d. of values obtained in 3 independent experiments. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ns, not significant.

Article Snippet: The CDK4/6 inhibitors (abemaciclib, palbociclib, ribociclib) and the specific NEK6 inhibitor ZINC05007751 was purchased from MedChem Express (Shanghai, China).

Techniques: Knock-Out, Single Cell Gel Electrophoresis, Concentration Assay, Immunofluorescence, Staining, Western Blot, Knockdown, Flow Cytometry

Journal: Frontiers in Pharmacology

Article Title: Genome-wide CRISPR screen identified NEK6 as a determinant of sensitivity to CDK4/6 inhibitor in endometrial cancer

doi: 10.3389/fphar.2025.1725886

Figure Lengend Snippet: The proposed model elaborating the mechanisms underlying NEK6 depletion enhanced CDK4/6 inhibitors sensitivity in EC.

Article Snippet: The CDK4/6 inhibitors (abemaciclib, palbociclib, ribociclib) and the specific NEK6 inhibitor ZINC05007751 was purchased from MedChem Express (Shanghai, China).

Techniques:

Journal: bioRxiv

Article Title: Cell-of-origin and genetic drivers define advanced bladder cancer subtypes and potential therapeutic response in mouse models

doi: 10.1101/2025.07.14.664768

Figure Lengend Snippet: In vitro analysis of mouse BC cell lines derived from K5-positive cells isolated from DKO (4K5; top) and QKO (K5.6; bottom) tumors: (A) sensitivity to palbociclib assessed by XTT assays. Data are presented as mean ± SEM; (B) Cell-cycle changes following palbociclib treatment for 48 hours at the IC 50 analyzed by flow cytometry; (C) Induction of PD-L1 expression after palbociclib treatment, depicting the percentage of live cells with high PD-L1 expression (left axis) and the mean fluorescence intensity (MFI) of PD-L1 (right axis), as assessed by flow cytometry. In B and C, data are presented as mean ± SD from three independent experiments, with the average value of each experiment shown as a single data point. D. In vivo evaluation of palbociclib monotherapy or combined with avelumab (anti-PD-L1) using immunocompetent syngeneic graft models of BC (DKO-K5, top; QKO-K5, bottom). Spider plots show normalized tumor growth curves for each treatment group relative to baseline. The dotted line indicates the threshold for non-responders, defined as half the average tumor volume of the control group. R = responders. E. Comparison of normalized tumor volumes (relative to baseline) between treatment groups at mid-treatment and the end of treatment for both models. Data from each individual are shown, along with the mean ± SD. C = control; P = palbociclib; A = avelumab; P+A = combination palbociclib plus avelumab. ns = not significant; *p-value< 0.05; **p- value< 0.01; ***p-value< 0.001; ****p-value< 0.0001.

Article Snippet: Palbociclib (CDK4/6 inhibitor) and avelumab (human anti-PD-L1 that recognized murine epitope) were provided by Pfizer SLU España (CPT Grant Request ID: 60314347, Project ID: WI235570).

Techniques: In Vitro, Derivative Assay, Isolation, Flow Cytometry, Expressing, Fluorescence, In Vivo, Control, Comparison