CSK (C-Terminal Src Kinase)

Compared with those of the Liuwei Dihuang Pills group, the expression level of p62, FcγRⅡB, SHP-1, and c-Src in the Liuwei Dihuang Pills + LV-shGPNMB group was significantly increased, and the level of LC3Ⅱ/LC3Ⅰ was significantly decreased. These results indicate that Liuwei Dihuang Pills can inhibit the FcγRⅡB/c-Src pathway by up-regulating the GPNMB expression, thereby increasing autophagy levels, enhancing neuroprotective ability, and alleviating Alzheimer's disease.

Washing column-bound GroEL/ES/Fgr with ATP-MgCl2 partially dissociated the chaperone complex, enabling isolation of pure Fgr through subsequent size-exclusion and ion exchange chromatography. This method reliably produced highly pure, active recombinant Fgr, with consistent yields of 1 mg per 2 liters of bacterial culture.

To elucidate the underlying mechanism, we conducted molecular dynamics simulations, which revealed critical binding interactions between compound 6 and CSK. Specifically, residues Phe333 and Met269 were found to play essential roles in mediating these interactions, providing valuable insights into the compound's mode of action.

In contrast, Csk knockdown and CA-Fyn commonly promote cell surface levels of L1-CAM, an immunoglobulin superfamily cell adhesion molecule that controls cortical neuronal migration. Thus, Csk-mediated local regulation of membrane-bound SFK activities appears essential for cortical neuronal migration through fine-tuning of intercellular attachment strength between immature neurons.

It was found to inhibit the c-Src-mediated kinase activity (IC50: 517 nM) in comparison to the positive control, bosutinib (IC50: 408 nM). The compound was also able to increase the oxidative stress and induce apoptosis in the colorectal cancer cells employed. The study thus may pave the way for exploration of the top identified ligands further to develop and establish their potential as c-Src kinase inhibitors with anticancer potential.

Understanding how estrogens induce metastasis will facilitate the development of better strategies to counteract the lethality of BC. Finally, the quantification of Snail may serve as a molecular marker in the early stages of tumor progression, as well as the use of drugs against c-Src and ERs, as they may be therapeutic targets.

It is noteworthy that the specific knockdown of SRCIN1 results in a reduction of key downstream gene targets within the Wnt/β-catenin axis, and tumors in mice treated with SRCIN1-targeting siRNA exhibit significantly smaller volumes (reduction exceeding 50%). Taken together, our study highlights the clinical and therapeutic relevance of SRCIN1 in thyroid cancer and suggests it as a potential therapeutic target for this disease.

Furthermore, both SI306 and Lipo-SI306 exhibited lower cytotoxicity towards HaCaT cells than dasatinib and gefitinib, with CC50s approximately one order of magnitude higher. Hemolytic activity (ranging from 1.85 % as liposomal formulation, to 3.81 % in DMSO and to 14.83 % in Tween80 MIX, respectively) and the median lethal dose (LD50) of 200 mg/kg on Tenebrio molitor coleoptera confirmed the favorable safety profile of SI306. Finally, pharmacokinetic and biodistribution studies in healthy mice showed prolonged circulation time and increased lung accumulation of SI306 when administered as liposomal formulation, highlighting the potential therapeutic advantages of this drug delivery system for NSCLC treatment.

In vivo experiments have demonstrated that MAZ knockdown inhibits tumorigenesis and metastasis in mice. Our findings highlight a novel mechanism wherein MAZ plays a transcriptional inhibitory role by recruiting HDAC1 to catalyze histone deacetylation, and the MAZ/HDAC1 complex inhibits CSK expression, thus promoting tumor proliferation and metastasis.

Lastly, The pro-proliferative effect of METTL3 on hepatocellular carcinoma was mechanistically linked to IRF1/c-Src axis activation, as evidenced by our experimental data. Results suggested that the METTL3/IRF1/c-Src axis played potential oncogenic roles in liver cancer development and the axis may be a promising therapeutic target in the disease.

Most of the tested compounds exhibited a better inhibitory activity and safety profile than the reference standard sunitinib malate against MIA-PaCa-2 and HCT-116 cancer cells...The tested compounds were observed to significantly reduce general TK activities in HCT-116 cell and induce apoptosis in HCT-116 and MIA-PaCa-2 cells. Lead compound 4e, the most effective general TKI, was determined to have a specific SRC kinase inhibitor effect in HCT-116 cell and the molecular modelling studies were performed to understand the potential binding mode at the ATP-binding domain of SRC kinase.

This review focuses on the research progress in several areas, including the mechanism of action, drug discovery, combination therapy, and clinical research. By presenting this information, we aim to provide researchers with convenient access to valuable insights and inspire new ideas to expedite future drug discovery programs.