In this study, we identified two previously described kinase inhibitors-3-(4-chloro-2-fluorobenzyl)-2-methyl-N-(3-methyl-1H-pyrazol-5-yl)-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine (LY2784544) and 1H-benzimidazole-4-carboxylic acid, 2-methyl-1-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-(4-morpholinyl)- (GSK2636771)-as novel GPR39 agonists by unbiased small-molecule-based screening ...

Phosphatidylinositol 3-kinase (PI3K) plays an important role in cell growth, proliferation and motility. The regulatory subunit, p85α, is the most abundantly expressed regulatory isoform of PI3K and is essential for the activation of PI3K. PI3K p85α is often over-expressed in colorectal cancer (CRC) cells, but its role in the migration and invasion of CRC remains unclear. In this study, lentivi...

OBJECTIVES Desensitization and down-regulation of -adrenergic receptors ( ARs) are prominent features of heart failure largely mediated by increased levels of AR kinase-1 ( ARK1). BACKGROUND -adrenergic receptor kinase 1 interacts with phosphoinositide-3 kinase (PI3K), and upon agonist stimulation, the ARK1/PI3K complex is recruited to agonist-stimulated ARs. Here we tested the hypothesis that ...

Objective(s): The current study was aimed to investigate the effect of morpholin-4-ium 4 methoxyphenyl (morpholino) phosphinodithioate (GYY4137) on ipsilateral epididymis injury in a rat model of experimental varicocele (VC).Materials and Methods: Sixty Wistar rats were randomly assigned to sham, sham plus GYY4137, VC and VC plus GYY4137...

Background and Objective: Oxidative stress induced by proinflammatory cytokines such as IL-1β plays a major role in β-cell destruction in diabetes type 1. Salvianolic acid B (Sal B) is a polyphenolic compound with antioxidant and protective effects. Thus, objective of this study was to assess the protection exerted by Sal B on isolated rat islets exposed to IL-1β and to investigate an underlyin...

background: the phosphatidylinositol 3-kinase/akt signaling pathway is recognized as a key driver of cancer cell survival and proliferation, and is often contingent upon an impairment of expression/function of the pten tumor suppressor, a negative regulator of this pathway. in addition, the cytoskeletal signaling protein tensin 2 has also been implicated as a negative regulator of this pathway....

Heliannuol is a sesquiterpene that has benzoxepine ring, oxepin. Many derivatives of compounds show anticancer activity by inhibiting the phosphoinositide 3-kinase (PI3K) enzyme. These enzymes play role in cell proliferation and growth. The study aims to predict physicochemical properties using Lipinski’s Rule Five parameters on 3- kinase (PI3K/Mtor; PDB 5OQ4) enzyme toxicity A, B, C, D, E comp...

Phosphoinositide-3 kinase (PI3K) signaling pathway alterations occur broadly in cancer and PI3K is a promising therapeutic target. Here, we investigated acquired resistance to GDC-0941, a PI3K inhibitor in clinical trials. Colorectal cancer (CRC) cells made to be resistant to GDC-0941 were discovered to secrete amphiregulin, which resulted in increased EGFR/MAPK signaling. Moreover, prolonged P...

Ewing sarcoma (ES) is the second most common pediatric bone cancer. Despite recent advances in treatment, patients with metastatic tumors have dismal prognosis and hence novel therapies are urgently needed to combat this A study has shown that phosphoinositide-3 kinase (PI3K) inhibitors can synergistically increase sensitivity bromodomain extraterminal domain ES cells therefore combined inhibit...