Synthesis and identification of a novel skeleton of N-(pyridin-3-yl) proline as a selective CDK4/6 inhibitor with anti-breast cancer activities.

CDK4/6 were attractive chemotherapeutic targets for the treatment of malignant tumors, CDK4/6 selective inhibitors have made outstanding contributions in the treatment of breast cancer. However, these inhibitors share a single skeleton of N-(pyridin-2-yl) pyrimidin-2-amine which cannot overcome the side effects in clinical application. In our previous study, an N'- acetylpyrrolidine-1-carbohydrazide was hit as the initial fragment by analyzing the active site characteristics of CDK6.

Synthesis and biological evaluation of novel ()--benzylidene hydrazides as novel c-Met inhibitors through fragment based virtual screening.

C-Met plays a crucial role in the development and progression of neoplastic disease. Type II c-Met inhibitors recognise the inactive DFG-out conformation of the kinase, result in better anti-tumour effects due to synergistic effect against the other kinases. According to our previous works, an benzylidene group was selected as the initial fragment.

Identification of Novel PI3Kδ Selective Inhibitors by SVM-Based Multistage Virtual Screening and Molecular Dynamics Simulations.

Phosphoinositide 3 kinase delta (PI3Kδ) is a lipid kinase that has been implicated in a variety of immune mediated disorders. The research on isoform selectivity was crucial for reducing side effects. In the current study, an optimized hierarchical multistage virtual screening method was utilized for screening the PI3Kδ selective inhibitors.

Identification of novel CDK2 inhibitors by a multistage virtual screening method based on SVM, pharmacophore and docking model.

Cyclin-dependent kinase 2 (CDK2) is the family of Ser/Thr protein kinases that has emerged as a highly selective with low toxic cancer therapy target. A multistage virtual screening method combined by SVM, protein-ligand interaction fingerprints (PLIF) pharmacophore and docking was utilised for screening the CDK2 inhibitors. The evaluation of the validation set indicated that this method can be used to screen large chemical databases because it has a high hit-rate and enrichment factor (80.

[Resveratrol reduces inflammatory cytokines via inhibiting nuclear factor-κB and mitogen-activated protein kinase signal pathway in a rabbit atherosclerosis model].

Objective: Inflammation serves as the initial pathologic step of cardiovascular diseases including atherosclerosis. Resveratrol possesses many pharmacological properties including antioxidant, cardioprotective and anti-cancer effects. In this study, we investigate the anti-inflammatory effect and mechanisms of resveratrol in an atherosclerotic rabbit model.

[VEGF165-induced angiogenesis by regulating intracellular free Mg2+ in HUVECs].

Aim: The mechanism of vascular endothelial growth factor165 (VEGF165) on intracellular free magnesium ([Mg2+]i) in human umbilical vein endothelial cells (HUVECs) was investigated.

Methods: [Mg2+]i in HUVECs loaded with fluorescent magnesium indicator mag-fura-2 were quantitatively detected the use of intracellular cation measurement system.

Results: VEGF165 significantly increased [Mg2+]i in the extracellular Mg2+ and this effect could be blocked by pretreatment with tyrosine kinase inhibitors (tyrphostin A23 and genistein), phosphatidylinositol 3-kinase (PI3K) inhibitors (wortmannin and LY294002) and phospholipase Cgamma (PLCgamma) inhibitor (U73122).