Triterpene and diterpene inhibitors of pyruvate dehydrogenase kinase (PDK).
Several oximes of triterpenes with a 17-beta hydroxyl and abietane derivatives are inhibitors of pyruvate dehydrogenase kinase (PDK) activity. The oxime 12 and dehydroabietyl amine 2 exhibit a blood glucose lowering effect in the diabetic ob/ob mouse after a single oral dose of 100 micromol/kg. However, the mechanism of the blood glucose lowering effect is likely unrelated to PDK inhibition.
Aicher
T D
TD
Metabolic & Cardiovascular Diesases Research, Novartis Institute for Biomedical Research, Summit, NJ 07901, USA.
Damon
R E
RE
Koletar
J
J
Vinluan
C C
CC
Brand
L J
LJ
Gao
J
J
Shetty
S S
SS
Kaplan
E L
EL
Mann
W R
WR
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D004224:Diterpenes / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use
D001786:Blood Glucose; D004224:Diterpenes; D047428:Protein Kinase Inhibitors; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D014315:Triterpenes; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases