azd1775  (MedChemExpress)

Journal: Breast Cancer Research : BCR

Article Title: Anti-cancer drug sensitivity testing and preclinical evaluation of the anti-cancer potential of WEE1 inhibitor in triple-negative breast cancer patient-derived organoids and xenograft models

doi: 10.1186/s13058-025-02063-0

Figure Lengend Snippet: Oral administration of AZD1775 suppressed tumor growth by increasing γH2AX phosphorylation while decreasing CDK1 phosphorylation and Ki67 expression in PDX mice. A Experimental design and timeline. B , C Tumor volume and body weights measured two times weekly in PDX mice treated with vehicle, or AZD1775 (30 mg/kg daily oral gavage) ( n = 5). D , E Gross images and wet weights ( n = 5) of PDX tumors. F , G Western blot images and densitometry band quantification ( n = 5) of p-WEE1, p-CDK1, and p-γH2AX normalized by ß-actin in PDX tumors. H Quantitative analysis ( n = 5) of immunohistochemistry of Ki67, p-CDK1, and p-γH2AX in tumors. All data were presented as mean ± standard deviation. * P < 0.05. ** P < 0.01. unpaired t-test. PDX, patient-derived xenograft; CDK1, cyclin-dependent kinase 1

Article Snippet: 15 , AZD1775 , Selleckchem , S1525 , 2 , 10 , 3 , DMSO , Liquid.

Techniques: Phospho-proteomics, Expressing, Western Blot, Immunohistochemistry, Standard Deviation, Derivative Assay

Journal: Breast Cancer Research : BCR

Article Title: Anti-cancer drug sensitivity testing and preclinical evaluation of the anti-cancer potential of WEE1 inhibitor in triple-negative breast cancer patient-derived organoids and xenograft models

doi: 10.1186/s13058-025-02063-0

Figure Lengend Snippet: AZD1775 led to abnormal G2/M arrest and increased p-γH2AX-positive aneuploid population, leading to aneuploidy, DNA damage, and cell death in PDXOs. A Western blot images of WEE1 in PDXOs. B , C Propidium iodide-based cell cycle analysis of cells with diploid and aneuploid DNA contents in PDXOs treated with AZD1775 (1, 2, and 4 µM) for 24 h using flow cytometry ( n = 4). D p-γH2AX detection in cells with diploid and aneuploid DNA contents in PDXOs treated with AZD1775 (1, 2, and 4 µM) for 48 h using flow cytometry. E Microscopy images of PDXOs treated with AZD1775 (IC 50 ) for 7 days. F The activity of Caspase 3/7 staining after 7 h exposure to IC 50 concentration of AZD1775 ( n = 3) ( G , H ) Representative images of PDXOs stained with Calcein-AM and Calcein fluorescence intensity ( n = 3) in PDXOs treated with 4 μM AZD1775 for 6 days. All data were presented as mean ± standard deviation. * P < 0.05. ** P < 0.01. *** P < 0.001 using unpaired t-test. PDX, patient-derived xenograft; PDXO, PDX-derived organoid; Calcein-AM; calcein- acetoxymethyl-ester

Article Snippet: 15 , AZD1775 , Selleckchem , S1525 , 2 , 10 , 3 , DMSO , Liquid.

Techniques: Western Blot, Cell Cycle Assay, Flow Cytometry, Microscopy, Activity Assay, Staining, Concentration Assay, Fluorescence, Standard Deviation, Derivative Assay

Journal: Breast Cancer Research : BCR

Article Title: Anti-cancer drug sensitivity testing and preclinical evaluation of the anti-cancer potential of WEE1 inhibitor in triple-negative breast cancer patient-derived organoids and xenograft models

doi: 10.1186/s13058-025-02063-0

Figure Lengend Snippet: PDOs and -PDXOs had a high concordance in their responses to anti-cancer medicines, including AZD1775. Scatter plots (correlation) of cell viability (%) against anti-cancer drugs at different concentrations in PDOs ( n = 3) and PDXOs ( n = 3). Perfect correlation, CCC > 0.99; Substantial correlation, 0.95 to 0.99; moderate correlation, 0.90 to 0.95; poor correlation, < 0.90. PDO, patient-derived organoid; PDXO, PDX-derived organoid; CCC; Lin’s Concordance Correlation Coefficient

Article Snippet: 15 , AZD1775 , Selleckchem , S1525 , 2 , 10 , 3 , DMSO , Liquid.

Techniques: Derivative Assay

Journal: Breast Cancer Research : BCR

Article Title: Anti-cancer drug sensitivity testing and preclinical evaluation of the anti-cancer potential of WEE1 inhibitor in triple-negative breast cancer patient-derived organoids and xenograft models

doi: 10.1186/s13058-025-02063-0

Figure Lengend Snippet: The workflow to establish a biobank with human TNBC-derived organoid lines and perform drug screening including WEE1 targeted therapy. A Schematic diagram showing the workflow. Both PDO and PDXO, which retained histological characteristics of human TNBC tumor tissue, are stored in a biobank and treated with anti-cancer drugs. B Proposed mechanism of action of the WEE1 inhibitor (AZD1775) in TNBC-derived organoid lines. AZD1775 inhibits the phosphorylation of WEE1, increasing CDK1 activity. This blockade leads to the abrogation of the G2/M checkpoint, which results in the accumulation of DNA damage, and finally triggers a mitotic catastrophe. TNBC; triple-negative breast cancer; PDO, patient-derived organoid; PDXO, PDX-derived organoid; CDK1, cyclin-dependent kinase 1

Article Snippet: 15 , AZD1775 , Selleckchem , S1525 , 2 , 10 , 3 , DMSO , Liquid.

Techniques: Derivative Assay, Drug discovery, Phospho-proteomics, Activity Assay