Chemical Property of Tosedostat
Chemical Property:
- Refractive Index:1.566
- PKA:9.44±0.40(Predicted)
- PSA：124.96000
- Density:1.245 g/cm3
- LogP:2.64010
- Storage Temp.:Store at -20°C
- Solubility.:≥40.6 mg/mL in DMSO; insoluble in H2O; ≥15.07 mg/mL in EtOH with ultrasonic
- XLogP3:2.3
- Hydrogen Bond Donor Count:4
- Hydrogen Bond Acceptor Count:6
- Rotatable Bond Count:10
- Exact Mass:406.21038668
- Heavy Atom Count:29
- Complexity:555
- Purity/Quality:
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99%, *data from raw suppliers
CHR 2797 *data from reagent suppliers
Safty Information:
- Pictogram(s):
- Hazard Codes:
- MSDS Files:
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SDS file from LookChem
Useful:
- Canonical SMILES:CC(C)CC(C(C(=O)NO)O)C(=O)NC(C1=CC=CC=C1)C(=O)OC2CCCC2
- Isomeric SMILES:CC(C)C[C@H]([C@@H](C(=O)NO)O)C(=O)N[C@@H](C1=CC=CC=C1)C(=O)OC2CCCC2
- Recent ClinicalTrials:Crossover Trial of the Effect of a High-Fat Meal on the PK of Oral CHR 2797 in Healthy Male Subjects
- Recent EU Clinical Trials:Phase II multicenter study of low dose Cytarabine + Tosedostat for previously untreated older patients with acute myeloid leukemia (AML)
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Description
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.
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Uses
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. 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 c
ell 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 in
hibitor, Bestatin. 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.
