Tosedostat is an inhibitor of aminopeptidases (IC50s = 100, 150, and 220 nM for LAP, PUSA, and aminopeptidase N, respectively). It inhibits proliferation of human leukemia cell lines in vitro irrespective of p53, PTEN, or K-RAS mutational status (IC50s = 10-770 nM). Tosedostat induces up-regulation of genes in amino acid transport and metabolic pathways and inhibits phosphorylation of mammalian target of rapamycin (mTOR) substrates in HL-60 cells, markers of amino acid depletion. In vivo, tosedostat (100 mg/kg) reduces total tumor burden and the number of spontaneous metastases in a mouse MDA-MB-435 xenograft model. Formulations containing tosedostat are under clinical investigation for the treatment of myeloid leukemia.
CHR-2797 is a novel metalloenzyme inhibitor that is converted into a pharmacological active acid product (CHR-79888) inside cells. CHR-2797 exerts antiproliferative effects against a range of tumor cell lines in vitro and in vivo and shows selectivity for transformed over nontransformed cells. Its antiproliferative effects are at least 300 times more potent than the prototypical aminopeptidase inhibitor, Bestatin.
Labelled Tosedostat
nst a range of tumor cell lines in vitro and in vivo and shows selectivity for transformed over nontransformed cells. Its antiproliferative effects are at least 300 times more potent than the prototyp
ical aminopeptidase inhibitor, Bestatin.
ChEBI: (2S)-2-[[(2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4-methyl-1-oxopentyl]amino]-2-phenylacetic acid cyclopentyl ester is a secondary carboxamide, a hydroxamic acid and a carboxylic ester.
Aminopeptidase inhibitor (IC 50 values are 100, 150, 220, > 1000, > 5000, > 10000 and > 30000 nM for LAP, PuSA, aminopeptidase N, aminopeptidase B, PILSAP, LTA 4 hydrolase and MetAP2 respectively). Potently inhibits tumor cell proliferation in a variety of tumor cell lines in vitro and in vivo .
