Pharmacological properties of SD-282 - an alpha-isoform selective inhibitor for p38 MAP kinase.
The effects of small-molecule p38 inhibitors in numerous models of different disease states have been published, including those of SD-282, an indole-5-carboxamide inhibitor. The aim of the present study was to evaluate the pharmacological activity of SD-282 on cytokine production in vitro as well as in 2 in vivo models of inflammation in order to illuminate the role of this particular inhibitor in diverse disease states. The results presented here provide further characterization of SD-282 and provide a context in which to interpret the activity of this p38 inhibitor in models of arthritis, pain, myocardial injury, sepsis and asthma; all of which have an inflammatory component. SD-282 represents a valuable tool to elucidate the role of p38 MAP kinase in multiple models of inflammation.
Koppelman
Bruce
B
Scios, Inc., Fremont, Calif., USA. bruce_koppelman@yahoo.com
Webb
Heather K
HK
Medicherla
Satyanarayana
S
Almirez
Ramona
R
Feng
Ying
Y
Chavez
Jose Carlos
JC
Mao
Cheng Ping
CP
Nguyen
Aaron
A
Liu
Yu-Wang
YW
Kapoun
Ann M
AM
Muiru
Gladys
G
Huang
Yuanying Anne
YA
Dugar
Sundeep
S
Mavunkel
Babu J
BJ
Lim
Don W
DW
Chakravarty
Sarvajit
S
Luedtke
Gregory
G
Protter
Andrew A
AA
Higgins
Linda S
LS
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D018805:Sepsis / Q000188:drug therapy / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D014409:Tumor Necrosis Factor-alpha; C514526:indole-5-carboxamide; D010047:Ovalbumin; D048051:p38 Mitogen-Activated Protein Kinases