Abe F, Kuramochi H, Takahashi K, Ishizuka M, Takeuchi T
Research Laboratories, Nippon Kayaku Co., Ltd., Tokyo, Japan.
J Antibiot (Tokyo). 1988 Dec;41(12):1862-7. doi: 10.7164/antibiotics.41.1862.
The biological activity of the two main metabolites of ubenimex in humans, (-)-N-[(2S,3R)-3-amino-2-hydroxy-4-(4'-hydroxy)phenylbutyryl]-L-leucine (OH-ubenimex) and (2S,3R)-3-amino-2-hydroxy-4-phenylbutyric acid [2S,3R)-AHPA) was examined. OH-Ubenimex was almost identical in inhibitory activity against mouse peritoneal resident macrophage aminopeptidases (APases) and the growth of IMC carcinoma in mice to ubenimex. In contrast, the inhibition of; mouse spleen cell APase activities in vitro, blastogenesis of mouse T and B cells in vitro, delayed cutaneous hypersensitivity in mice, and the growth of C1498 leukemia and HeLa S3 cells in vitro was weaker than ubenimex. Macrophage APase activity was only slightly inhibited by (2S,3R)-AHPA which also had practically no activity in the other biological assays.
对乌苯美司在人体内的两种主要代谢产物，（-）-N-[(2S,3R)-3-氨基-2-羟基-4-(4'-羟基)苯基丁酰基]-L-亮氨酸（OH-乌苯美司）和(2S,3R)-3-氨基-2-羟基-4-苯基丁酸[(2S,3R)-AHPA]的生物活性进行了研究。OH-乌苯美司对小鼠腹腔驻留巨噬细胞氨肽酶（APases）的抑制活性以及对小鼠IMC癌生长的抑制活性与乌苯美司几乎相同。相比之下，其对体外小鼠脾细胞APase活性、体外小鼠T和B细胞的母细胞生成、小鼠迟发型皮肤超敏反应以及体外C1498白血病和HeLa S3细胞生长的抑制作用比乌苯美司弱。(2S,3R)-AHPA对巨噬细胞APase活性的抑制作用较弱，并且在其他生物测定中实际上也没有活性。
