BACKGROUND: Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2) is activated upon stress by p38 MAPK. MK2 is stimulated in a wide range of inflammatory conditions and its catalytic activity is required for cytokine production, cell migration and is a potential drug target for inflammatory diseases. Disruption of MK2 leads to a reduction in TNF-alpha production. MK2-mediated pro-inflammatory cytokine production has been demonstrated in several inflammatory conditions where TNF-alpha plays a role. OBJECTIVE/ METHODS: We discuss the development of specific MK2 inhibitors for the treatment of inflammatory diseases. RESULTS/ CONCLUSION: Inhibition of the p38 MAPK pathway may have therapeutic uses for inflammatory diseases. However, blocking p38 MAPK activation in vivo is not advisable due to toxicity, significant off-target effects, and lack of oral bioavailability. This concern may be countered by the use of MK2 inhibitors that can dissect the pathways downstream of p38 without affecting additional cellular functions.
BACKGROUND: Mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2) is activated upon stress by p38 MAPK. MK2 is stimulated in a wide range of inflammatory conditions and its catalytic activity is required for cytokine production, cell migration and is a potential drug target for inflammatory diseases. Disruption of MK2 leads to a reduction in TNF-alpha production. MK2-mediated pro-inflammatory cytokine production has been demonstrated in several inflammatory conditions where TNF-alpha plays a role. OBJECTIVE/ METHODS: We discuss the development of specific MK2 inhibitors for the treatment of inflammatory diseases. RESULTS/ CONCLUSION: Inhibition of the p38 MAPK pathway may have therapeutic uses for inflammatory diseases. However, blocking p38 MAPK activation in vivo is not advisable due to toxicity, significant off-target effects, and lack of oral bioavailability. This concern may be countered by the use of MK2 inhibitors that can dissect the pathways downstream of p38 without affecting additional cellular functions.
Authors: Lale Ozcan; Xiaoming Xu; Shi-Xian Deng; Devram S Ghorpade; Tiffany Thomas; Serge Cremers; Brian Hubbard; Michael H Serrano-Wu; Matthias Gaestel; Donald W Landry; Ira Tabas Journal: Diabetes Date: 2015-06-11 Impact factor: 9.461
Authors: José M C Ribeiro; Fernando A Genta; Marcos H F Sorgine; Raquel Logullo; Rafael D Mesquita; Gabriela O Paiva-Silva; David Majerowicz; Marcelo Medeiros; Leonardo Koerich; Walter R Terra; Clélia Ferreira; André C Pimentel; Paulo M Bisch; Daniel C Leite; Michelle M P Diniz; João Lídio da S G V Junior; Manuela L Da Silva; Ricardo N Araujo; Ana Caroline P Gandara; Sébastien Brosson; Didier Salmon; Sabrina Bousbata; Natalia González-Caballero; Ariel Mariano Silber; Michele Alves-Bezerra; Katia C Gondim; Mário Alberto C Silva-Neto; Georgia C Atella; Helena Araujo; Felipe A Dias; Carla Polycarpo; Raquel J Vionette-Amaral; Patrícia Fampa; Ana Claudia A Melo; Aparecida S Tanaka; Carsten Balczun; José Henrique M Oliveira; Renata L S Gonçalves; Cristiano Lazoski; Rolando Rivera-Pomar; Luis Diambra; Günter A Schaub; Elói S Garcia; Patrícia Azambuja; Glória R C Braz; Pedro L Oliveira Journal: PLoS Negl Trop Dis Date: 2014-01-09
Authors: Xiaohua Huang; Gerald W Shipps; Cliff C Cheng; Peter Spacciapoli; Xingmin Zhang; Mark A McCoy; Daniel F Wyss; Xianshu Yang; Abdelghani Achab; Kyle Soucy; Donna K Montavon; Denise M Murphy; Charles E Whitehurst Journal: ACS Med Chem Lett Date: 2011-06-24 Impact factor: 4.345
Authors: Jun Qin; Pawan Dhondi; Xianhai Huang; Robert Aslanian; James Fossetta; Fang Tian; Daniel Lundell; Anandan Palani Journal: ACS Med Chem Lett Date: 2011-12-23 Impact factor: 4.345
Authors: Robert Cheng; Brunella Felicetti; Shilpa Palan; Ian Toogood-Johnson; Christoph Scheich; John Barker; Mark Whittaker; Thomas Hesterkamp Journal: Protein Sci Date: 2010-01 Impact factor: 6.725
Authors: Linda D Bobo; Rana E El Feghaly; Yee-Shiuan Chen; Erik R Dubberke; Zhuolin Han; Alexandra H Baker; Jinmei Li; Carey-Ann D Burnham; David B Haslam Journal: Infect Immun Date: 2012-12-21 Impact factor: 3.441