Tosedostat

SKU: orb1300889

Description

Tosedostat (CHR-2797) is an orally active aminopeptidase inhibitor prodrug. Its intracellular metabolite, CHR-79888, targets M1 family enzymes like PuSA and LTA4 hydrolase, inducing amino acid deprivation and apoptosis in cancer cells. It has been investigated in preclinical and clinical studies for hematological malignancies and solid tumors.

Research Area

Metabolism Research, Neuroscience

Key Properties

• CAS Number: 238750-77-1
• MW: 406.47
• Purity: 98.86%
• Formula: C₂₁H₃₀N₂O₆
• SMILES: CC(C)C[C@H]([C@H](O)C(=O)NO)C(=O)N[C@H](C(=O)OC1CCCC1)c1ccccc1
• Target: AChR,Aminopeptidase
• Solubility: DMSO:55 mg/mL (135.31 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (4.92 mM)

Bioactivity

• In Vivo:
  In vivo in rodent cancer models, Tosedostat (CHR-2797) has anticancer activity, and a dose-response relationship has been shown in two models. The effect of Tosedostat is less apparent when the tumor burden is higher before therapy.
• In Vitro:
  In HL-60 cells, the treatmentwith Tosedostat (CHR-2797) results in an increase in the secretion of Stanniocalcin 2 (STC2) protein into the growth medium. After 2 h treatment with Tosedostat (60 nM), increases in SLC7A11 expression are detectable. The for by Tosedostat inhibits the proliferation of U-937 and HuT 78 cell lines (IC50s: 10 nM; >10 μM). Tosedostat treatment increases expression of amino acid deprivation response (AADR) genes in U-937 cells but not in HuT 78 cells. By 24 h with Tosedostat (0.01 μM) the mean MCA production is reduced to 77.8% of the untreated control cells; similarly the MCA production is reduced to 51.3% with 1 μM, 38.5% with 5 μM, and 35.3% with 10 μM Tosedostat.
• Cell Research:
  Tosedostat (CHR-2797) is stored at -20°C as a 10 mM stock in dimethyl sulfoxide (DMSO), and diluted with RPMI culture medium prior to use.Leukemic cells are washed and suspended in phosphate buffered saline (PBS). 100 μL of cell suspension (1×105 cells/mL) is mixed with 100 μL of Tosedostat (CHR-2797) (0.01 to 10 μM) and 200 μM L-alanine 4-methyl-coumaryl-7-amide (ala-MCA) in a 96 well plate in duplicate. The aminopeptidase activity is measured by detecting the fluorescent 7-amino-4-methylcoumarin (MCA) liberated from the cleavage of ala-MCA by cellular aminopeptidases (excitation 355 nm, emission 460 nm).
• Animal Research:
  A breeding colony of NOD/SCID IL2R gammanull mice are used in this study. The mice are inoculated subcutaneously in the right flank with 2×106 H929 myeloma cells in 50 μL RPMI-1640 and 50 μL MatrigelTM Basement Membrane Matrix Growth Factor Reduced. The mice are assigned into the following four treatment groups (10 animals per group): no treatment, Tosedostat 75 mg/kg, CHR-3996 30 mg/kg, and Tosedostat 75 mg/kg with concomitant CHR-3996 30 mg/kg. Tosedostat is administered daily by intra-peritoneal injection beginning four days after the tumour cells are inoculated. Caliper measurements of the longest perpendicular tumour diameters (length) and width are performed every other day to estimate the tumour volume.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Aminopeptidase, CHR 2797, CHR2797, CHR-2797, Inhibitor, inhibit, M1-aminopeptidase, Tosedostat

Compound Identifiers

PubChem CID

15547703