MK2: a novel molecular target for anti-inflammatory therapy.
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
We discuss the development of specific MK2 inhibitors for the treatment of inflammatory diseases.


CONCLUSIONS
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.
Duraisamy
Senthil
S
Ranbaxy Research Laboratories, New Drug Discovery Research, Department of Pharmacology, Plot No-20, Sector-18, Gurgaon-122001-Haryana, India.
Bajpai
Malini
M
Bughani
Usha
U
Dastidar
Sunanda G
SG
Ray
Abhijit
A
Chopra
Puneet
P
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000099190:MAP-Kinase-Activated Kinase 2
D000894:Anti-Inflammatory Agents, Non-Steroidal; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D000099190:MAP-Kinase-Activated Kinase 2