海洋天然物の新しい薬理活性 : 沖縄産海綿の生産するagelasphinを母化合物とするKRN7000の開発

概要

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New glycosphingolipids, named agelasphins, have been isolated as antitumoral compounds from an extract of a marine sponge, Agelas mauritianus. The absolute configurations of agelasphins were elucidated by the total synthesis. Various analogues of agelasphins were also synthesized and the relationship between their structures and biological activities was examined using an MLR assay. From the results, KRN7000, (2S, 3S, 4R)-1-O(α-D-galactopyranosyl)-2-(N-hexacosanoylamino)-1, 3, 4-octadecanetriol, was selected as a candidate for clinical application. KRN7000 markedly stimulated lymphocytic proliferation in allogeneic MLR, and showed potent tumor growth inhibitory activities in B16-bearing mice and strongly inhibited tumor metastasis, suggesting that KRN7000 is a potent biological response modifier. These biological effects were exerted by the activation of dendritic cells by KRN7000.