WEE1 (Phospho-Ser642) Antibody
- Known as:
- WEE1 (Phospho-Ser642) Antibody
- Catalog number:
- 11706
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Signalway
- Gene target:
- WEE1 (Phospho-Ser642) Antibody
Related genes to: WEE1 (Phospho-Ser642) Antibody
- Gene:
- WEE1 NIH gene
- Name:
- WEE1 G2 checkpoint kinase
- Previous symbol:
- -
- Synonyms:
- WEE1A
- Chromosome:
- 11p15.4
- Locus Type:
- gene with protein product
- Date approved:
- 1992-08-06
- Date modifiied:
- 2016-07-28
Related products to: WEE1 (Phospho-Ser642) Antibody
Related articles to: WEE1 (Phospho-Ser642) Antibody
- Cutaneous T-cell lymphomas (CTCL), most commonly mycosis fungoides and Sézary syndrome, are rare non-Hodgkin lymphomas. Advanced disease responds poorly to current treatments, highlighting the need for new molecularly targeted therapies. WEE1 is a central regulator of the G2/M checkpoint and S-phase progression and has emerged as a therapeutic target in several malignancies, yet it has not been systematically explored in CTCL. We screened a library of more than 2200 kinase inhibitors in CTCL cell lines and selected adavosertib for further study. Its effects were tested in four CTCL lines; primary keratinocytes and fibroblasts; patient-derived malignant CD4 T cells and healthy donor CD4 T cells; and a MyLa xenograft model, using viability, apoptosis, cell-cycle, Western blot, and phospho-protein array assays. Adavosertib reduced viability at submicromolar IC values (0.26-0.56 µM) across all four CTCL lines while largely sparing primary skin cells and was more active in malignant than in healthy donor CD4 T cells. It induced apoptosis and cell-line-specific S-phase and/or G2/M accumulation, lowered WEE1 and phospho-CDK1 (Tyr15), and increased phospho-H2A.X. A phospho-protein array showed activation of checkpoint and stress signalling. In a preliminary xenograft experiment, adavosertib slowed MyLa tumour growth. These preclinical data identify WEE1 as a therapeutic target in CTCL and support further preclinical and early-phase clinical evaluation of adavosertib in this disease. - Source: PubMed
Publication date: 2026/08/28
Özistanbullu DenizBahrami KarolaDoll MonikaReichenbach GabiPöschl Sarah MWilhelm RaphaelStege HennerZöller NadjaWinkler LarsJäger ManuelNicolay Jan PQuist Sven RKaufmann RolandMeissner MarkusSchilling BastianKleemann JohannesCinatl JindrichKippenberger Stefan - WEE1 kinase is a main regulator of the G2/M cell cycle checkpoint. It plays an important role in maintaining genomic stability by inhibiting CDK1 through a phosphorylation process at Tyr15. WEE1 is found to be overexpressed in several cancers and also act as a protective mechanism that allows cancer cells to repair DNA damage and survive under replicative stress. So, pharmacological inhibition of WEE1 has emerged as a promising therapeutic strategy. Many conventional chemotherapeutic agents act by inducing DNA damage, so it enables the activation of WEE1 in cancer cells to arrest the cell cycle and repair this damage by preventing cell death. Inhibition of WEE1 disrupts this protective checkpoint, which ultimately leads to mitotic catastrophe. Therefore, targeting WEE1 represents a promising and rational therapeutic approach, mainly in tumors with TP53 mutations. We have comprehensively discussed the structural features of WEE1, its regulation in DNA damage response, epigenetic control, and its role in cancer progression. We have also summarized the clinical development of major WEE1 inhibitors such as adavosertib, azenosertib (ZN-c3), and Debio 0123. Moreover, recently synthesized small-molecule inhibitors are also discussed with special focus on structure-activity relationship (SAR) insights, dual-target inhibitors, and PROTACs and molecular glue-based degraders. Two compounds, 8 and 11, were found to be the most potent WEE1 inhibitors with excellent enzymatic inhibition. This explains the importance of rational scaffold optimization and electron-withdrawing group insertion for enhanced activity. Overall, this review serves as a valuable reference for medicinal chemists in the development of next-generation WEE1 inhibitors. See also the graphical abstract(Fig. 1). - Source: PubMed
Publication date: 2026/07/24
Kumar AnkushPaudel Keshav RajKaur RajwinderBhatia Rohit - The DNA damage response (DDR) is a sophisticated network of cellular pathways whose perturbation leads to genome instability and is a key hallmark of oncogenesis. Here, we present data from 32 genome-scale loss-of-function CRISPR interference chemical-genetic screens with inhibitors targeting core constituents of the DDR machinery (PARP, ATR, ATM, DNAPK and WEE1), as both single agents and in combination with poly(ADP-ribose) polymerase inhibitors. These experiments identify >1,000 genes whose perturbation modifies the DDR and provides a rich resource to the DDR community. In addition, this compendium of functional genomics data reveals key principles governing the DDR and highlights a strong chemical-genetic interaction between loss of activity of the peroxiredoxin PRDX1 and all tested DDR inhibitors through a mechanism involving iron availability mediated by an MRGBP-PAX7-IREB2 axis. Our data position PRDX1 as a key suppressor of DNA damage accumulation and potential druggable target in combination with DDR inhibitors. - Source: PubMed
Publication date: 2026/09/08
O'Loughlin Thomas AArab AbolfazlMisiukiewicz SaraMontesano ElizabethYogodzinski ChristopherBorah Ashir AQuarantotti ValentinaLou KevinRosen Barry SCorn Jacob EGianni DavideKabir ShaheenForment Josep VGilbert Luke A - Podocyte injury and loss in diabetic nephropathy (DN) are driven by mitotic catastrophe (MC), a disastrous cell death caused by aberrant cell cycle re-entry. Ten-eleven translocation 2 (TET2), a 5-methylcytosine (m5C) RNA demethylase, was upregulated in DN and regulated cell proliferation. Here, we explored whether TET2 mediates podocyte MC in DN using Adriamycin (ADM) and high glucose (HG) in vitro, and both STZ-induced and db/db diabetic mouse models in vivo. TET2 was upregulated in human diseased kidneys and injured podocytes, and its expression correlated with disease severity and podocyte loss. EdU staining and flow cytometry verified that ADM/HG facilitated cell proliferation and G2/M phase transition via elevated CDK1-cyclin B1 phosphorylation; meanwhile, ADM/HG increased reactive oxygen species and malondialdehyde levels. TET2 overexpression further enhanced ADM/HG-induced podocyte MC and oxidative stress, whereas TET2 knockdown had the opposite effect. Mechanistically, TET2 reduced Wee1 mRNA stability in an m5C-dependent manner, leading to CDK1-cyclin B1 activation. Rescue experiments confirmed that Wee1 reintroduction rescued TET2-driven MC and oxidative stress, while Wee1 silencing abolished the protection from TET2 knockdown. In vivo, TET2 depletion or Wee1 overexpression alleviated podocyte MC, renal injury, and apoptotic podocytes in both diabetic models. Collectively, TET2 promotes podocyte MC and aggravates DN via TET2-mediated m5C demethylation that suppresses Wee1 expression and activates CDK1-cyclin B1, suggesting that this axis may represent a candidate pathway in the context of DN. - Source: PubMed
Publication date: 2026/09/05
Feng JieDong HongjuanYang YiXie LiyiLu WanhongGuo YuruiKong Ranran - The timing of DNA replication and centrosome duplication is tightly regulated with cell cycle progression to ensure the faithful duplication of the genome during cell division. Both DNA and centrosomes are licensed for replication in late telophase/early G1, replicated in S phase and segregated during mitosis; yet how defects in DNA replication licensing are coupled to centrosome homeostasis remains poorly understood. Here, we show that depletion of the replication licensing inhibitor Geminin in proliferating mouse embryonic fibroblasts induces robust centrosome amplification together with impaired primary cilium assembly. Rather than promoting whole-genome reduplication, knockdown of Geminin triggers a replication stress response, characterized by DNA damage accumulation throughout the cycle, and activation of an ATR-dependent DNA damage response. Mechanistically, Geminin depletion-induced replication stress activates the ATR-Chk1-Wee1 checkpoint axis prolonging G2 and leading to premature centriole disengagement and centrosome amplification. These findings identify replication stress as the signaling module that couples defective DNA replication licensing to centrosome amplification. - Source: PubMed
Publication date: 2026/07/02
Santos Inês BGlover David M