Target Validation Information
TTD ID	T15610
Target Name	Puromycin-sensitive aminopeptidase (NPEPPS)
Type of Target	Clinical trial
Drug Potency against Target	CHR-2797	Drug Info	IC50 = 150 nM	[2]
Action against Disease Model	CHR-2797	Drug Info	CHR-79888 is a potent inhibitor of a n uMber of intracellular aminopeptidases, including leucine aminopeptidase. CHR-2797 treatment in the h uMan promyelocytic leukemia cell line HL-60 induced a transcriptional response indicative of amino acid depletion, the amino acid deprivation response, which involves up-regulation of amino acid synthetic genes, transporters, and tRNA synthetases. These changes were confirmed in other leukemic cell lines sensitive to the antiproliferative effects of CHR-2797. Furthermore, CHR-2797 treatment inhibited phosphorylation of mTOR substrates and reduced protein synthesis in HL-60 cells, both also indicative of amino acid depletion. Treatment with CHR-2797 led to an increase in the concentration of intracellular small peptides, the substrates of aminopeptidases.	[1]
References
REF 1	CHR-2797: an antiproliferative aminopeptidase inhibitor that leads to amino acid deprivation in human leukemic cells. Cancer Res. 2008 Aug 15;68(16):6669-79.
REF 2	A first-in-man phase i and pharmacokinetic study on CHR-2797 (Tosedostat), an inhibitor of M1 aminopeptidases, in patients with advanced solid tumors. Clin Cancer Res. 2009 Aug 1;15(15):4978-85.

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