MAP Kinase <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> en-US <p><strong>PAGEPress</strong> has chosen to apply the&nbsp;<a href="" target="_blank" rel="noopener"><strong>Creative Commons Attribution NonCommercial 4.0 International License</strong></a>&nbsp;(CC BY-NC 4.0) to all manuscripts to be published.<br><br> An Open Access Publication is one that meets the following two conditions:</p> <ol> <li>the author(s) and copyright holder(s) grant(s) to all users a free, irrevocable, worldwide, perpetual right of access to, and a license to copy, use, distribute, transmit and display the work publicly and to make and distribute derivative works, in any digital medium for any responsible purpose, subject to proper attribution of authorship, as well as the right to make small numbers of printed copies for their personal use.</li> <li>a complete version of the work and all supplemental materials, including a copy of the permission as stated above, in a suitable standard electronic format is deposited immediately upon initial publication in at least one online repository that is supported by an academic institution, scholarly society, government agency, or other well-established organization that seeks to enable open access, unrestricted distribution, interoperability, and long-term archiving.</li> </ol> <p>Authors who publish with this journal agree to the following terms:</p> <ol> <li>Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.</li> <li>Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.</li> <li>Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.</li> </ol> (Paola Granata) (Tiziano Taccini) Thu, 22 Oct 2015 16:40:41 +0000 OJS 60 Clinical candidates of small molecule p38 MAPK inhibitors for inflammatory diseases 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. Li Xing ##submission.copyrightStatement## Tue, 19 Jan 2016 16:30:40 +0000 JNK inhibitors: is there a future? 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. Jonas Cicenas ##submission.copyrightStatement## Mon, 28 Dec 2015 18:21:14 +0000 Expression of ERK1 and ERK2 in prostate cancer 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. Norelia Torrealba, Benito Fraile, Gabriel Olmedilla, Pilar Martínez-Onsurbe, Manuel Guil-Cid, Ricardo Paniagua, Mar Royuela ##submission.copyrightStatement## Fri, 18 Dec 2015 18:23:47 +0000