Design and synthesis of highly potent fumagillin analogues from homology modeling for a human MetAP-2.
New fumagillin analogues were designed through structure-based molecular modeling with a human methionine aminopeptidase-2. Among the fumagillin analogues, cinnamic acid ester derivative CKD-731 showed 1000-fold more potent proliferation inhibitory activity on endothelial cell than TNP-470.
Han
C K
CK
Chong Kun Dang Research Institute, Chungcheongnamdo, South Korea.
Ahn
S K
SK
Choi
N S
NS
Hong
R K
RK
Moon
S K
SK
Chun
H S
HS
Lee
S J
SJ
Kim
J W
JW
Hong
C I
CI
Kim
D
D
Yoon
J H
JH
No
K T
KT
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000737:chemistry*; D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002934:Cinnamates / Q000138:chemical synthesis / Q000494:pharmacology; D003510:Cyclohexanes; D015195:Drug Design; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis* / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007941:Leukemia P388 / Q000473:pathology; D008666:Metalloendopeptidases / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012717:Sesquiterpenes; D013329:Structure-Activity Relationship
D020533:Angiogenesis Inhibitors; D002934:Cinnamates; D003510:Cyclohexanes; D004852:Epoxy Compounds; D005231:Fatty Acids, Unsaturated; D006131:Growth Inhibitors; D012717:Sesquiterpenes; C404215:CKD 731; C026211:fumagillin; D000626:Aminopeptidases; C106541:methionine aminopeptidase 2; D008666:Metalloendopeptidases