It seems the chances of success n To be higher than ever before. Small molecule inhibitors of protein kinases are h Frequently developed for the treatment of a variety of human diseases. p38  for such small molecules for the treatment of cancer and inflammation. Lapatinib Tykerb SB203580 and SB202190 inhibitors are the most widely used of the p38 MAPK. The portal W Daughters of threonine 106 in the groove binding p38a ATP has been shown that the most important determinant of the specificity of t This class of compounds. The majority of known protein kinases, a bulky residue T106 Equivalents position carrying the binding of SB203580 and SB202190 prevented.
Although the compounds SB has been designed to specifically inhibit the a and b isoforms of p38 MAPK, which have the suppression of inflammatory gene expression, subsequent studies various other targets of protein kinase these compounds confinement Lich the identified GAK, GSK3B, RICK, casein kinase I, type II TGF-receptor, LCK, CRAF, BRAF and PDK1. Zus Tzlich were h Here concentrations of SB discovered compounds inhibitory effects on multiple targets non-protein kinases, such as cytochrome P450 enzymes, cyclooxygenase and thromboxane synthase to have. SB202190 has been shown to autophagic vacuoles and cell death in a specific cancer c Lon induce. This observation has recently been leased to ovarian cancer cells agrees on and have proposed an r Important for the p38 MAPK and SB202190 serious therapeutic potential for the treatment of cancer c Lon.
The observed macroautophagy is an evolution Rer process w held During the differentiation and development of dam Ftigt consisting of sequestration of cytoplasmic proteins and organelles in autophagosome with a further deterioration of autophagolysosomes. W Hrstoffen while the main regulator of autophagy mTOR, which regulates the rate of autophagy in response to the availability of N, Recent studies the importance of p38 MAPK and ERK 1/2 signaling shown the formation and maturation of autophagic vacuoles in response to hunger and more chemical Descr ONS. Furthermore, the inhibition of p38 MAPK by SB202190 was transcriptional reprogramming passing HIF 1adependent to 3A Foxo-dependent-Dependent gene expression pro autophagic proved what to induce programmed cell death involves Type II.
Vacuoles of SB compounds were induced Unweighted Similar high and therefore not t in contrast to the blockade of autophagy happy space that efficient autophagic flux. Here we examined the effect of SB202190, to better characterize the nature of the cell response specific vacuolation and r P38 MAPK in autophagy. Fa She unexpectedly, our results show that neither inhibition of p38 MAPK or Ver changes In the expression of genes required for autophagy response mediated SB202190 that seems cell type-specific, but not cancer. Instead, SB202190 engages with different pathway, including normal PI3K/Akt/mTOR signaling k responsible for the observed autophagic response Nnte. Results SB202190 induced cytoplasmic vacuoles in a cell fa Type specific to transformed and untransformed SB202190 on the h Most common used inhibitor of p38 MAPK.