Anti-CDK2 monoclonal antibody, clone 2D5

This study aimed to investigate the role of long non-coding RNA (lncRNA) taurine up-regulated 1 (TUG1) in the development of ulcerative colitis (UC) and to explore the underlying mechanisms. A murine model of UC was induced by dextran sodium sulfate (DSS) exposure. The colonic epithelial YAMC cells were treated with TNF-alpha to simulate the inflammatory environment of intestinal epithelial cells (IECs). RNA pull-down and RIP assays were performed to analyze the interaction between TUG1 and HuR. Luciferase activity assay was conducted to evaluate the interaction between TUG1 and miR-29b-3p. Cell proliferation was evaluated by MTT assay. Cell apoptosis was assessed by flow cytometry and western blot analysis of apoptosis-related proteins. TUG1 overexpression promoted cell proliferation and inhibited cell apoptosis in the TNF-alpha-stimulated YAMC cells. The mechanistic analysis showed that TUG1 positively regulated the HuR/c-myc axis via its interaction with HuR, leading to upregulation of c-myc expression; meanwhile, TUG1 negatively regulated the miR-29b-3p/CDK2 signaling via binding to miR-29b-3p, leading to derepression of CDK2 expression. Further animal experiments showed that TUG1 overexpression attenuated UC progression in the DSS-induced UC in mice. Collectively, TUG1 inhibits IEC apoptosis and UC progression by regulating the balance of HuR and miR-29b-3p.

In connection with our research program concerning development of novel effective benzimidazole-based anticancer candidates, herein we describe a new unexpected synthetic route to obtain a series of 2-((imidazole/benzimidazol2-yl)thio)1-arylethanones endowed with promising anti-breast cancer and Cyclin-dependent kinase 2 (CDK2) inhibitory activities. Contrary to expectations, products for the reaction of 2-mercaptoimidazole/benzimidazole 2a,b with beta-keto esters 6a-c were unambiguously assigned as 2-((imidazol/benzimidazol2-yl)thio)1-arylethanones 10a-f based on NMR spectroscopy and single-crystal X-ray crystallographic analyses. In vitro anticancer activities for herein reported imidazole/benzimidazoles 10a-f were assessed through a cell-based assay against human breast cancer T4-7D and MCF-7 cell lines. Benzimidazoles 10d-f exerted better anti-proliferative action towards T4-7D and MCF-7 cell lines than their corresponding imidazole counterparts 10a-c. Furthermore, a molecular docking study suggested CDK2 kinase as a potential enzymatic target for benzimidazoles 10d-f, and investigated their possible binding pattern and interactions within CDK2 active site. Thereafter, benzimidazoles 10d-f were in vitro examined for their CDK2 inhibitory action, where they exerted good activity. Finally, several key ADME and druglikeness properties were predicted by the SwissADME online tool. Interestingly, benzimidazoles 10d-f were found to have no violations in all druglikeness rules (Veber, Lipinski, Ghose, Muegge, and Egan). In addition, they had neither PAINS nor structural alerts (Brenks). In conclusion, benzimidazoles 10d-f demonstrated not only a promising anticancer activities but also an acceptable ADME and physicochemical properties especially benzimidazole 10e.