Structure-activity relationship of alpha-galactosylceramides against B16-bearing mice.
Agelasphin-9b, (2S,3S,4R)-1-O-(alpha-D-galactopyranosyl)-16-methyl-2- [N-((R)-2- hydroxytetracosanoyl)-amino]- 1,3,4-heptadecanetriol, is a potent antitumor agent isolated from the marine sponge Agelas mauritianus. Various analogues of agelasphin-9b (a lead compound) were synthesized, and the relationship between their structures and biological activities was examined using several assay systems. From the results, KRN7000, (2S,3S,4R)-1-O-(alpha-D- galactopyranosyl)-2-(N-hexacosanoylamino)-1,3,4-octadecanetriol , was selected as a candidate for clinical application.
Morita
M
M
Pharmaceutical Research Laboratory, Kirin Brewery Company, Ltd., Gunma, Japan.
Motoki
K
K
Akimoto
K
K
Natori
T
T
Sakai
T
T
Sawa
E
E
Yamaji
K
K
Koezuka
Y
Y
Kobayashi
E
E
Fukushima
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005312:Fetal Blood; D005699:Galactosylceramides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011161:Porifera / Q000737:chemistry; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D005699:Galactosylceramides