Tosedostat

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.Formal Name: alphaS-[[(2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4-methyl-1-oxopentyl]amino]-benzeneacetic acid, cyclopentyl ester. CAS Number: 238750-77-1. Synonyms: CHR-2797. Molecular Formula: C21H30N2O6. Formula Weight: 406.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 10 mg/ml, DMSO: 20 mg/ml, Ethanol: 5 mg/ml. lambdamax: 205 nm. SMILES: O=C(OC1CCCC1)[C@@H](NC([C@]([C@H](O)C(NO)=O)([H])CC(C)C)=O)C2=CC=CC=C2. InChi Code: InChI=1S/C21H30N2O6/c1-13(2)12-16(18(24)20(26)23-28)19(25)22-17(14-8-4-3-5-9-14)21(27)29-15-10-6-7-11-15/h3-5,8-9,13,15-18,24,28H,6-7,10-12H2,1-2H3,(H,22,25)(H,23,26)/t16-,17+,18+/m1/s1. InChi Key: FWFGIHPGRQZWIW-SQNIBIBYSA-N.