NU7441

Collectively, our findings highlight the therapeutic potential of KU-57788 in ATC while revealing an intrinsic resistance mechanism mediated by DRP1 activation and the potential involvement of the NRF2/SLC7A11/GSH axis. More importantly, we provide strong evidence that combining KU-57788 with ferroptosis inducers significantly enhances its anticancer efficacy, offering a promising therapeutic strategy for ATC.

This study highlights the prognostic relevance of MRGs in BLCA. The nine-gene signature may serve as a useful framework for risk stratification in BLCA, while the identified risk genes and candidate compounds provide a basis for further biological and experimental investigation rather than direct therapeutic inference.

Three genes (MXRA7, PLEKHG4B and ATP2B4) were identified to construct a SERG-related model in BLCA, which provides a basis for understanding BLCA pathogenesis and new insights into BLCA treatment.

This study identifies ATT-1 as a promising multi-targeted therapeutic for colorectal cancer by leveraging PDOs for direct, de novo target discovery. We uniquely identified two novel, high-affinity targets, CLTC and XRCC5, and elucidated a convergent dual-targeting mechanism wherein ATT-1 binding disrupts DNA damage repair and triggers apoptosis. This novel mechanism and its potent synergy with standard chemotherapy in physiologically relevant models provide a compelling strategy for integrating traditional Chinese medicine into modern precision oncology.

Glioblastoma (GBM) remains one of the deadliest primary brain tumors, with rapid recurrence and near-universal resistance to temozolomide (TMZ) limiting long-term survival...Inhibition of PRKDC with the ATP-competitive inhibitor KU57788 reversed resistance, restoring TMZ sensitivity and impairing tumor growth in vivo...These results establish the LMNA-PRKDC axis as a functional driver of TMZ resistance through enhanced DNA repair capacity in stem-like tumor subpopulations. Our findings support pharmacologic inhibition of PRKDC as a rational strategy to resensitize resistant GBM to standard chemotherapy and offer a foundation for future biomarker-driven clinical trials targeting DNA repair vulnerabilities in recurrent disease.

Drug sensitivity analysis revealed that high-PCDS patients may benefit more from agents like sorafenib and fulvestrant, while low-PCDS patients responded better to NU7441. Notably, the PCDS is closely associated with key immunological characteristics of the TME. These findings advance personalized treatment strategies and support clinically relevant decision-making in DLBCL.

Among 47 drugs with notable IC50 variations, Ribociclib, PD173074, KU-55933, NU7441, and nutlin-3a exhibited lower IC50 values within the low-risk group, whereas Lapatinib demonstrated greater efficacy among the high-risk group. RT-qPCR validation confirmed the robustness of the model. We successfully verified a new model of molecular markers of MDSCs-related lncRNAs, offering critical insights for predicting outcomes and guiding therapeutic decisions in BRCA cases.

Furthermore, several targeted drugs, including MK-2206, pazopanib, JNK inhibitor VIII, PLX4720, and NU-7441, were associated with risk scores. This study identified five TRP-related biomarkers associated with RC prognosis, providing novel insights into the role of TRP channels in RC development. These findings may contribute to a deeper understanding of RC pathogenesis and offer potential targets for personalized therapy.

Pharmacological inhibitors, KU55933 (ATM), NU7441 (DNA-PK), and VE821 (ATR), also sensitized V79, CHO, and U2OS human cancer cells to Taxol. These findings suggest that ATM, ATR, and DNA-PK not only facilitate DNA repair but also suppress Taxol-induced apoptosis via caspase-3. Their inhibition may represent a promising strategy to boost their efficacy of Taxol and potentially enhance responses to radiation therapy through combined targeting of mitotic stress and DDR pathways.

Our study identifies a CAF subpopulation, COL10A1+Fib, associated with CRC progression and immune suppression, suggesting it as a potential therapeutic target in CRC and possibly other malignancies.

In vitro experiments demonstrated that MLL-AF9-overexpressing B-ALL cells exhibited reduced sensitivity to doxorubicin (DOX), cyclophosphamide (CTX), and cisplatin (DDP). Chemoresistance was effectively reversed by the ABC transporter inhibitor Verapamil and the NHEJ inhibitor NU7441 in in vitro and in vivo models. These findings highlight MLL-AF9's role in mediating chemoresistance via ABCB1 and the NHEJ pathways, offering potential therapeutic targets for MLL-AF9-positive B-ALL.

The slices were irradiated using 137Cs, either with or without a DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441)...In the organotypic model, radiation alone in DNA-PK-deficient SCID mice and radiation combined with DNA-PK inhibition in C57BL/6 mice led to increased residual γH2AX and 53BP1 staining. This study demonstrates that residual DNA damage levels following ionizing radiation in lung tissue are comparable between in vivo and ex vivo tissue slices, suggesting that PCLSs serve as a valuable organotypic model for investigating the effects of drug-radiation combinations.