Hemodynamic effects of potent and selective JNK inhibitors in anesthetized rats: implication for targeting protein kinases in metabolic diseases.
The hemodynamic effects of a series of potent and selective 4-aminopyridine carboxamide-based pan-JNK inhibitors were assessed in an anesthetized rat model. The effects of these agents on mean arterial pressure, heart rate, cardiac contractility, and peripheral vascular resistance are described, and the implication for targeting protein kinases in metabolic diseases is discussed.
Liu
Gang
G
Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6101, USA. gang.liu@abbott.com
Zhao
Hongyu
H
Liu
Bo
B
Xin
Zhili
Z
Liu
Mei
M
Serby
Michael D
MD
Lubbers
Nathan L
NL
Widomski
Deborah L
DL
Polakowski
James S
JS
Beno
David W A
DW
Trevillyan
James M
JM
Sham
Hing L
HL
D000631:Aminopyridines / Q000138:chemical synthesis / Q000494:pharmacology; D000758:Anesthesia; D000777:Anesthetics; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors*; D008297:Male; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000201:enzymology*; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013874:Thiopental / Q000031:analogs & derivatives; D014655:Vascular Resistance / Q000187:drug effects*; D016277:Ventricular Function, Left / Q000187:drug effects
D000631:Aminopyridines; D000777:Anesthetics; D004791:Enzyme Inhibitors; C004316:thiobutabarbital; D048670:MAP Kinase Kinase 4; D013874:Thiopental