Biological activity of the main metabolites of ubenimex in humans

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.