scholarly journals Use of p38 MAPK Inhibitors for the Treatment of Werner Syndrome

2010 ◽  
Vol 3 (6) ◽  
pp. 1842-1872 ◽  
Author(s):  
Mark C. Bagley ◽  
Terence Davis ◽  
Paola G. S. Murziani ◽  
Caroline S. Widdowson ◽  
David Kipling
Keyword(s):  
P38 Mapk ◽  
Werner Syndrome ◽  
P38 Mapk Inhibitors ◽  
Mapk Inhibitors

scholarly journals Microwave-assisted synthesis of a pyrazolyl ketone library for evaluation as p38 MAPK inhibitors in Werner syndrome cells

2010 ◽  
Vol 2 (2) ◽  
pp. 203-213 ◽  
Author(s):  
Mark C Bagley ◽  
Terence Davis ◽  
Matthew C Dix ◽  
Paola GS Murziani ◽  
Michal J Rokicki ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Werner Syndrome ◽  
Microwave Assisted Synthesis ◽  
Microwave Assisted ◽  
P38 Mapk Inhibitors ◽  
Mapk Inhibitors

Docking, synthesis and pharmacological activity of novel urea-derivatives designed as p38 MAPK inhibitors

2012 ◽  
Vol 54 ◽  
pp. 264-271 ◽  
Author(s):  
Raquel de Oliveira Lopes ◽  
Nelilma Correia Romeiro ◽  
Cleverton Kleiton F. de Lima ◽  
Leandro Louback da Silva ◽  
Ana Luisa Palhares de Miranda ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Pharmacological Activity ◽  
Urea Derivatives ◽  
P38 Mapk Inhibitors ◽  
Mapk Inhibitors

Ligand-based 3D pharmacophore design, virtual screening and molecular docking for novel p38 MAPK inhibitors

2014 ◽  
Vol 24 (2) ◽  
pp. 797-809 ◽  
Author(s):  
Lijuan He ◽  
Ru Dai ◽  
Xuan R. Zhang ◽  
Si Y. Gao ◽  
Yan Y. He ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
P38 Mapk ◽  
3D Pharmacophore ◽  
P38 Mapk Inhibitors ◽  
Mapk Inhibitors

scholarly journals Effects of p38 MAPK inhibitors on fibroblast differentiation in the zone of postoperative scar formation

2018 ◽  
pp. 43-47
Author(s):  
Ирина Александровна Шурыгина ◽  
Н.В. Зеленин ◽  
Г.Б. Гранина ◽  
М.Г. Шурыгин
Keyword(s):  
P38 Mapk ◽  
Wistar Rats ◽  
Scar Formation ◽  
Control Group ◽  
P38 Inhibitor ◽  
P38 Mapk Inhibitors ◽  
Mapk Inhibitors ◽  
P38 Mapk Inhibitor ◽  
Postoperative Scar ◽  
Mapk Inhibitor

Цель исследования: оценить влияние блокатора р38 МАРК SB203580 на дифференцировку фибробластов в зоне формирования послеоперационного рубца. Материалы и методы: На модели линейной кожно-мышечной раны у крыс линии Вистар оценено влияние локального введения блокатора р38 МАРК SB203580 в составе лекарственной пленки на дифференцировку фибробластов (n = 30) по сравнению с заживлением раны без введения активного вещества (n = 30). Проводили оценку количества коллагена в области раны, периоперационной зоне и интактной дерме, а также иммуноморфологическое окрашивание на CD34, CD45, ММР9 и актин в сроки от 2 часов до 30 суток. Результаты: Установлено, что применение блокатора р38 SB203580 приводило к значительному снижению интенсивности коллагенообразования в зоне формирующегося рубца. Так, у животных контрольной группы относительная площадь, занятая волокнами коллагена в зоне послеоперационной раны, закономерно возрастала в сроки от 3 до 30 суток, достигая максимальных значений к концу наблюдения - 73,54% [66,87; 78,01]. При введении SB203580 в течение всего срока наблюдения отмечалось достоверное снижение коллагенообразования в сравнении с группой контроля, к 30 суткам показатель составил 43,60% [41,05; 60,15] (р = 0.002). Введение SB203580 снижало привлечение прогениторных клеток фибробластического ряда в зону формирования послеоперационного рубца, повышало фиброкластическую активность. Aim. To assess effects of a p38 MAPK inhibitor, SB203580, on fibroblast differentiation in the zone of postoperative scar formation. Materials and methods. The effect of locally injected p38 MAPK inhibitor, SB203580, on fibroblast differentiation (n = 30) was compared with wound healing without an active substance injection (n = 30) on a model of linear musculocutaneous wound in Wistar rats weighing 220-250 g. We measured the amount of collagen in the wound zone, perioperative zone, and intact derma and conducted immunomorphological staining for CD34, CD45, MMP9, and actin at timepoints of 2 hours to 30 days. Results. The p38 inhibitor, SB203580, induced a significant decrease in collagenation intensity in the zone of forming scar. In Wistar rats of the control group, the percent area of collagen fibers in the zone of postoperative wound was increasing between days 3 and 30 and reached a maximum of 73.54 % [66.87; 78.01] by the end of observation period. The SB203580 injection significantly decreased collagenation over the entire period of observation compared with the control group (43.60 % [41.05; 60.15] by day 30, р = 0.002). The SB203580 injection decreased the engagement of fibroblastic progenitors in the zone of postoperative scar formation and increased the fibroclast activity.

scholarly journals The Expanding Role of p38 Mitogen-Activated Protein Kinase in Programmed Host Cell Death

2019 ◽  
Vol 12 ◽  
pp. 117863611986459 ◽  
Author(s):  
Jessica Gräb ◽  
Jan Rybniker
Keyword(s):  
Protein Kinase ◽  
Host Cell ◽  
P38 Mapk ◽  
Bacterial Infections ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Host Cell Apoptosis ◽  
Mitogen Activated Protein ◽  
P38 Mapk Inhibitors ◽  
Mapk Inhibitors

The p38 mitogen-activated protein kinase (MAPK) is involved in a multitude of essential cellular processes. The kinase is activated in response to environmental stresses, including bacterial infections and inflammation, to regulate the immune response of the host. However, recent studies have demonstrated that pathogens can manipulate p38 MAPK signaling for their own benefit to either prevent or induce host cell apoptosis. In addition, there is evidence demonstrating that p38 MAPK is a potent trigger of pathogen-induced necrosis driven by mitochondrial membrane disruption. Given the large number of p38 MAPK inhibitors that have been tested in clinical trials, these findings provide an opportunity to repurpose these drugs for improved control of infectious diseases.

p38 MAPK Inhibitors Ameliorate Target Organ Damage in Hypertension: Part 1. p38 MAPK-Dependent Endothelial Dysfunction and Hypertension

2003 ◽  
Vol 307 (3) ◽  
pp. 932-938 ◽  
Author(s):  
Haisong Ju ◽  
David J. Behm ◽  
Sandyha Nerurkar ◽  
Marianne E. Eybye ◽  
Robin E. Haimbach ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
P38 Mapk ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Target Organ ◽  
P38 Mapk Inhibitors ◽  
Mapk Inhibitors

P38 MAPK: critical molecule in thrombin-induced NF-κB-dependent leukocyte recruitment

2003 ◽  
Vol 284 (4) ◽  
pp. H1095-H1103 ◽  
Author(s):  
Jaswinder Kaur ◽  
Richard C. Woodman ◽  
Paul Kubes
Keyword(s):  
P38 Mapk ◽  
Umbilical Vein ◽  
Nuclear Factor Κb ◽  
Flow Chamber ◽  
Significant Inhibition ◽  
Leukocyte Recruitment ◽  
P38 Mapk Inhibitors ◽  
Mapk Inhibitors ◽  
Umbilical Vein Endothelial Cells ◽  
Sb 203580

Thrombin-stimulated endothelium synthesizes numerous adhesion molecules to recruit leukocytes; however, it is unknown which intracellular pathways are responsible for this event. A recent report from our laboratory has shown that thrombin induces E-selectin expression and that blocking nuclear factor-κB (NF-κB) activity partially blocked both E-selectin expression (60%) and leukocyte recruitment. In this study, we systematically assessed the importance of p38 MAPK in thrombin-induced NF-κB activation and E-selectin-dependent leukocyte recruitment. Thrombin caused phosphorylation of p38 MAPK, its substrate ATF-2, and JNK MAPK, but not ERK MAPK. The p38 MAPK inhibitors, SKF86002 and SB-203580 only reduced ATF-2 activity. We treated human umbilical vein endothelial cells with SKF86002, 1 h before thrombin stimulation, and noted inhibition of NF-κB mobilization and complete inhibition of leukocyte rolling and adhesion in a laminar flow chamber. Significant inhibition of leukocyte recruitment and E-selectin expression was also observed with SB-203580. SKF86002 did not affect other systems, including tumor necrosis factor-α-induced E-selectin-dependent leukocyte recruitment. Moreover, thrombin-induced rapid mobilization of P-selectin from Weibel Palade bodies was not p38 MAPK dependent. These data suggest that thrombin induces p38 MAPK activation, which leads to NF-κB mobilization to the nucleus and causes the upregulation of E-selectin and subsequent leukocyte recruitment.

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