It’s been no significant improvement in the primary Ren endpoint containing CrOhn,’s Disease Activity Index and endoscopy. C-reactive protein, which temporarily reduced in the drug-treated group, suggesting that there be mechanisms to escape p38 regulation or k Pharmacokinetic Nnten problems with penetration / drug. Confusion aspect of the study was the inclusion of a MPC-3100 large number of patients s from Russia, that distinguish placebo reactions and other clinical characteristics of the cohort of Western Europe seem. ERK inhibitors in rheumatic diseases have not advanced as much as the other two families of MAP kinase. Most of the attention is focused on the cancer because r Leading the ERK plays in the regulation of cell growth. Pleased t that directly inhibit ERK regulate the recent efforts by targeting upstream kinases, ERK.
PD0325901 in a Phase 1 study in 41 patients with melanoma and other cancers was studied. The compound reduced the phosphorylation of ERK in tumors and several partial responses were observed. Toxicity t With rash and Sehst Changes BAY 73-4506 have combined with a certain H Reports abundance. These side effects were considered to be a mechanism-based, but can be managed by adjusting the dose of MEK or dosage regimen for inhibitors. STRATEGIES FOR THE FUTURE MAP kinase inhibitor development definitive proof of concept demonstration of the usefulness of the MAP kinase inhibitors in inflammatory diseases in humans, neurodegenerative or b Sartig is still insufficient. Previous studies have typically t by the toxicity Ineffectiveness or confused, in some cases F, These two problems are related because to avoid the side effects of investigators from achieving optimal drug exposure for a sufficient time.
However, the data on p38 inhibitors are not yet inspiring. H Here selectivity t P38 over other kinases that Erh hung Specificity of t of the alpha-isoform of p38, or the development of allosteric inhibitors is pleased t that ATP competitors k Nnten the toxicity Improve t profile. Specificity t Problems k Can be especially difficult when drugs are directed to the site of the kinase ATP since a betr Chtliche homology between the different enzymes in the kinome. Therefore provide allosteric inhibitors that bind to other sites is an interesting alternative. Side effects can k Also targeted a kinase downstream Rts MAPKAPK 2 instead be minimized by p38 itself, as this protein is probably responsible for the cytokine-regulatory properties of p38 in macrophages.
38 k Nnte also target upstream kinases Suppress rts signaling responses, the inflammatory arthritis, but not defense contribute h themselves and / or Hom homeostasis. Studies suggest that inhibition MKKS MKK3 k Nnte advantage of p38 inhibition of cytokine-mediated inflammation, offer h while sparing defense Yourself and TLR responses. MKK7 Pleased t that MKK4 regulates cytokine-induced activation of JNK and is another m Possible target.39 Therefore targeting a MKK individual permit separation of MAP kinase activation of certain pathogenic normal reactions. CONCLUSION MAP kinases are attractive targets for rheumatic diseases, despite the setbacks Ge.