Furthermore, G-749 is screened and identified as a novel NAT10 inhibitor capable of effectively impeding lysosomal acidification and tumor metastasis by disrupting the NAT10-Ubiquitin-specific Peptidase 39 (USP39) interaction. Overall, the results unveil a novel role of ac4C modifications in regulating lysosomal acidification and propose a potential strategy by targeting NAT10 to inhibit esophageal cancer metastasis.

The ZMYM2-ANXA9 signaling axis drives chemoresistance and tumor progression in CRC. FLT3 inhibition by G749 effectively downregulates ANXA9 and sensitizes tumors to chemotherapy, highlighting a novel therapeutic approach for chemoresistant CRC.

Last, we identified a few correlations between the expression of CCR8 and TNFRSF9 and sensitivity to several drugs, including COL-3, Chlorambucil and GSK1070916, in pan-cancer. Overall, these findings highlight new evidence that both Treg signatures are crucial regulators of cancer progression, providing potential clinical outcomes for cancer therapy.

Then, screening of 8199 compounds by HTS2 assay identified that treatments of Hesperadin and GSK1070916 significantly mimic the expression pattern of the LINC00973 knockdown gene signature...Clinically, we further found that breast tumors with high expression of LINC00973 also show relatively high expression of AURKB or JUN, and vice versa. In summary, we established a novel high-throughput screening strategy to identify small molecules capable of targeting RNA, provided two promising compounds targeting LINC00973 and further shed light on the underlying transcriptional upregulation mechanism of LINC00973 within cancer cells.

To discover next-generation FLT3 inhibitors and gather additional structure-activity relationship (SAR) information, we performed structural modifications of G-749 (denfivontinib) utilizing structure simplification and scaffold hopping strategies...Furthermore, it significantly reduced reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP), and strongly inhibited FLT3-mediated signaling pathways. These findings, along with the obtained SAR information, provide valuable insights for the further development of FLT3 inhibitors.

To demonstrate the extent to which our findings reflect clinical results, we analyzed bulk-RNA sequencing data from 21 NSCLC patients undergoing anti-PD-1 immunotherapy. The NLRP3 inflammasome score influenced enhanced immune responses in patient data undergoing anti-PD-1 immunotherapy, suggesting a role for NLRP3 inflammasome in activating immune responses during treatment.

We validated tumor suppressive activities of the AURKB inhibitor (AURKBi) Barasertib (AZD1152-HQPA) and the structurally unrelated compound GSK-1070916 in cerebellum slice culture models for SHH, and Grp3 MB...We revealed that the combination of AURKBi with the SRC/BCR-ABL inhibitor Dasatinib acts synergistically to repress tumor growth and expansion in the highly invasive MB cell model ONS-76, but not in Grp3 MB cells...In conclusion, we demonstrate that AURKB is essential for MB tumor growth and expansion in the tissue context and the inhibition of AURKB is equally efficient as irradiation in repressing tumor cell growth. In patients younger than three years, pharmacological targeting of AURKB may thus constitute a novel means to overcome radiotherapy limitations.

We demonstrated that Paclitaxel (microtubule stabilizer), Palbociclib (cyclin dependent kinase 4/6 inhibitor), AZD1152 and GSK1070916 (aurora kinase B inhibitors) have anti-cancer functions beyond arresting cell cycle. We observed a trend that Paclitaxel suppressed STINGWT HCC more effectively than STINGKO HCC, suggesting that STING might contribute to the anti-tumor effects of Paclitaxel. Our study revealed the immune-mediated tumor-suppressing properties of cell cycle inhibitors and suggested combined treatment with immunotherapy as a potential therapeutic approach.

P1, N=36, Active, not recruiting, Oscotec Inc. | Recruiting --> Active, not recruiting

P1, N=14, Completed, Oscotec Inc. | Unknown status --> Completed | N=40 --> 14

BI-847325 showed a broader range of activity than the MEK inhibitor GDC-0623. In conclusion, dual MEK/Aurora kinase inhibition shows remarkable potential for treating multiple types of hematological and solid tumors. The combination with capecitabine was synergistic in colorectal, gastric, and mammary cancer.

However, they display opposite effects, circ/linVRK1 favors apoptosis whereas circ/linMAN1A2 stimulates cell migration, and only XL765 did not alter the ratio of other dangerous circ/linRNAs in MCF-7. In MDA-MB-231 cells, AMG511 and GSK1070916 decreased circGFRA1, as a good response to drugs. Furthermore, some circRNAs might be associated with specific mutated pathways, such as the PI3K/AKT in MCF-7 cells with circ/linHIPK3 correlating to cancer progression and drug-resistance, or NHEJ DNA repair pathway in TP-53 mutated MDA-MB-231 cells.