MAP Kinase 2016-06-23T11:08:05+00:00 Paola Granata Open Journal Systems <p><strong>MAP Kinase</strong> is an international, peer-reviewed online journal, publishing articles in all areas of biology and medicine relevant to mitogen activated protein kinases. Topics covered by the journal are biochemistry, protein structure, cell biology, molecular biology, pharmacology, neurobiology, molecular endocrinology, molecular oncology, clinical oncology, developmental biology, physiology and proteomics. <strong>MAP Kinase</strong> publishes reviews, research articles and database articles.</p> Clinical candidates of small molecule p38 MAPK inhibitors for inflammatory diseases 2016-06-23T11:08:03+00:00 Li Xing The trigger and etiology of chronic inflammatory diseases are not well understood, hindering the development of efficient therapeutic approaches. The observation that abnormal activity of the p38 MAPK is common to all inflammatory diseases raised the expectation that p38 inhibitors would serve as general anti-inflammatory therapeutics. A large number of inhibitors were consequently discovered. Several compounds of different scaffolds, blocking the p38 MAPK signaling pathway, have entered phase II clinical trials for rheumatoid arthritis, chronic obstructive pulmonary disease, pain, cardiovascular diseases, and cancer. As I review here, in almost all cases the clinical trials have failed, leading to re-design of compounds and re-evaluation of p38 as a suitable target. I describe how structural features, unique to p38<span>α</span>, have been employed in the inhibitor design and achieved high degree of kinome selectivity. I then focus on some of the drugs that reached human trials and summarize their <em>in vitro/in vivo</em> pharmacological profiles and the related outcomes from clinical investigations. These compounds include VX-745, VX-702, RO-4402257, SCIO- 469, BIRB-796, SD-0006, PH-797804, AMG-548, LY2228820, SB-681323 and GW-856553. Finally, I discuss novel suggested approaches for the use of p38 inhibitors such as combining p38 inhibition with inhibiting other targets that function in parallel inflammatory pathways for achieving efficacy in treating inflammatory diseases. 2016-01-19T16:30:40+00:00 ##submission.copyrightStatement## JNK inhibitors: is there a future? 2016-06-23T11:08:05+00:00 Jonas Cicenas JNK is a subfamily of MAP kinases that hat regulates a range of biological processes implicated in response to stress, such as cytokines, ultraviolet irradiation, heat shock, and osmotic shock as well as growth factors like PDGF, EGF, FGF, <em>etc</em>. They were originally identified as kinases that bind and phosphorylate JUN on S63 and Se73 within its transcriptional activation domain. The deregulation of these kinases is shown to be involved in human diseases, such as cancer, immune diseases and neurodegenerative disorders. The realization of the therapeutic potential of the inhibition of JNKs led to a thorough search for small-molecule inhibitors first for research purposes, but later also for therapeutic applications. Here, we discuss some of the most well-known JNK inhibitors and their use in basic research or clinical science. 2015-12-28T18:21:14+00:00 ##submission.copyrightStatement## Expression of ERK1 and ERK2 in prostate cancer 2016-06-23T11:07:58+00:00 Norelia Torrealba Benito Fraile Gabriel Olmedilla Pilar Martínez-Onsurbe Manuel Guil-Cid Ricardo Paniagua Mar Royuela Prostate cancer may emerge as result of dysregulated balance between cell proliferation and death rates, increased angiogenesis and chronic. These processes are regulated by numerous signaling proteins, including the mitogen-activated protein kinases (MAPKs). JNK, p38 and extracellular signal-regulated kinase (ERK) are the three major sub-families of MAPKs. The pro-oncogenic effects of ERK isoforms (ERK1 and ERK2) lie in their aberrant activation through phosphorylation by any mutation along the pathway of receptor tyrosine kinase (RTK)-Ras-Raf-MEK-ERK1/2. Once activated, ERKs phosphorylate cytoskeletal proteins, kinases, and transcription factors. Active ERK proteins induce strong proliferative and anti-apoptotic effects. Our group has tested variations in expression, activation and localization of ERKs in human prostate. Differential ERK1/2 expression and phosphorylation status may be linked to the progression of prostate cancer. The major striking observation is that ERKs are expressed in tumors with higher proportion than normal prostate. We believe that this is an important notion because the status (expression, localization, phosphorylation and the ERK1/ERK2 ratio) of ERK in the prostate may be developed into an important prognostic marker that predicts patient responce to the anti-cancer treatment. 2015-12-18T18:23:47+00:00 ##submission.copyrightStatement##