Guided by a scaffold-hopping strategy based on G-749 (denfivontinib), a series of quinazoline-based derivatives was designed and synthesized to explore structure-activity relationships (SAR)...Mechanism studies indicated that W4 induced G0/G1 cell cycle arrest and apoptosis, accompanied by a reduction in intracellular reactive oxygen species levels and a loss of mitochondrial membrane potential. Collectively, these results identified W4 as a potent FLT3 inhibitor and provided valuable SAR insights for further scaffold optimization.
P2, N=30, Completed, Department of Radiation Oncology, the First Medical Center, Chinese People's Liberation Army (PLA) General Hospital; The First Medical Center, Chinese
The effect of RT (8 and 3 × 8 Gy) on Interferon beta (IFNβ), IFN-stimulated genes (ISGs), and HLA-class-I expression in combination with IFN-type-I-response inhibitors (Ruxolitinib, Tofacitinib, Amlexanox) targeting the JAK and TBK1 was studied with Flow cytometry and RT-PCR. The current study supports the theory that baseline autophagy, RT-induced autophagy blockage, and IFN-type-I response enhancement define the HLA-class-I levels in NSCLC cells. This complex interplay emerges as a promising target for the development of radio-vaccination strategies to enhance the efficacy of radio-immunotherapy.
2 months ago
Journal • IO biomarker
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ATG7 (Autophagy Related 7) • IFNB1 (Interferon Beta 1) • MAP1LC3A (Microtubule Associated Protein 1 Light Chain 3 Alpha)