Tosedostat

**Semantic type:** Pharmacologic Substance

**Definition:** A proprietary orally bioavailable inhibitor of the M1 family of aminopeptidases with potential antineoplastic activity. Aminopeptidase inhibitor CHR-2797 is converted intracellularly into a poorly membrane-permeable active metabolite (CHR-79888) which inhibits the M1 family of aminopeptidases, particularly puromycin-sensitive aminopeptidase (PuSA), and leukotriene A4 (LTA4) hydrolase; inhibition of these aminopeptidases in tumor cells may result in amino acid deprivation, inhibition of protein synthesis due to a decrease in the intracellular free amino acid pool, an increase in the level of the proapoptotic protein Noxa, and cell death. Noxa is a member of the BH3 (Bcl-2 homology 3)-only subgroup of the proapoptotic Bcl-2 (B-cell CLL/lymphoma 2) protein family.

**Synonyms:** - Aminopeptidase inhibitor CHR-2797 - CHR 2797 - CHR-2797 - CHR2797 - Cyclopentyl (2S)-2-{(2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4- methylpentanamido}-2-phenylacetate - TOSEDOSTAT