Merck Research Laboratories, MSD, Oss, The Netherlands.
Published: June 2011
AI Article Synopsis
Article Abstract
MK2 kinase is a promising drug discovery target for the treatment of inflammatory diseases. Here, we describe the discovery of novel MK2 inhibitors using X-ray crystallography and structure-based drug design. The lead has in vivo efficacy in a short-term preclinical model.
Zika virus (ZIKV) outbreaks occur sporadically in tropical and subtropical regions. At present, there are no licensed vaccines or specific treatments available for ZIKV. Ivermectin is approved for use in humans as an antiparasitic drug.
Urinary tract infections are among the most frequently occurring forms of infection, and inflammation and tissue damage contribute significantly to symptoms, e.g., dysuria and urge.
Shiga toxins (Stxs), produced by serotype 1 and certain pathotypes, cause hemorrhagic colitis, which can progress to hemolytic uremic syndrome (HUS) and central nervous system (CNS) pathology. The underlying mechanisms of toxin-induced inflammation remain unclear. The p38 mitogen-activated protein kinase (MAPK) and its downstream target, MAPKAPK2 (MK2), play key roles in various cellular responses.
Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA; McCance Center for Brain Health, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address:
Alzheimer's disease (AD) poses significant treatment challenges, particularly targeting amyloid-β (Aβ), but a new analysis method uncovered 83 dysfunctional pathways relevant to AD in both human brains and lab models.
The p38 MAPK pathway was notably upregulated and linked to tau pathology and neuronal damage, highlighting its potential as a therapeutic target.
By using integrative pathway activity analysis (IPAA), researchers can combine human data with cellular models to efficiently identify promising drug targets for AD treatment.*
Microtubule-targeting agents (MTAs) have been successfully translated from basic research into clinical therapies and have been widely used as first- and second-line chemotherapy drugs for various cancers. However, current MTAs exhibit positive responses only in subsets of patients and are often accompanied by side effects due to their impact on normal cells. This underscores an urgent need to develop novel therapeutic strategies that enhance MTA efficacy while minimizing toxicity to normal tissues.
