.product-side h2 span {width: 50%;}.product-side h2 span.hover {}Related ProductsMolarity CalculatorDilution Calculator Tosedostat (CHR2797)Aminopeptidase inhibitorCatalog No.A4355SizePriceStockQty1mg$142.00In stock 10mg$303.00In stock Tel: +1-832-696-8203Email: sales@apexbt.comWorldwide Distributors Add to CartBulk InquiryFree samples Check OutSample solution is provided at 25 µL, 10mM.Product Citations1.Drinkwater, Nyssa, et al. "X‐ray crystal structures of an orally available aminopeptidase inhibitor, Tosedostat, bound to anti‐malarial drug targets PfA‐M1 and PfA‐M17." Proteins: Structure, Function, and Bioinformatics (2015).PMID:25645579Quality Control Quality Control & MSDS View current batch: 21 Purity = 98.00% COA (Certificate Of Analysis) MSDS (Material Safety Data Sheet) Datasheet Purity = 99.63% COA (Certificate Of Analysis) HPLC NMR (Nuclear Magnetic Resonance) MSDS (Material Safety Data Sheet)Datasheet Chemical structure Related Biological Data Biological ActivityDescriptionTosedostat is an aminopeptidase inhibitor of LAP, PuSA and Aminopeptidase N with IC50 values of 100 nM, 150 nM and 220 nM, respectively.TargetsLAPPuSAAminopeptidase NIC50100 nM150 nM220 nMProtocolCell experiment [1]:Cell linesHuman multiple myeloma (MM) cellsPreparation methodThe solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.Reacting condition10 μM, 72 hoursApplicationsCHR2797 showed antiproliferative and apoptotic effects against MM in vitro by inducing the AA deprivation response (AADR). Using MTS and CTG assays, CHR2797, at clinically achievable concentrations, decreased survival and proliferation in MM1S and IL-6-dependent ANBL6 cells, in the presence or absence of bone marrow stromal cells following 72 hours incubation. CHR2797 induced apoptosis in MM cells via activation of Caspase 3/7 and 9 but not Caspase 8. CHR2797 (10 μM) induced apoptosis in patient MM cells. Combined treatment with CHR2797 and LBH589 in MM cells (MM1S, ANBL6, and INA6) further reduced cell viability following 72 hour incubation when compared with CHR2797 treatment alone. CHR2797 (1 μM) in combination with LBH589 (1 nM) showed an increased growth arrest in G0/G1 cells in MM1R cells treated with both drugs versus CHR2797 alone after 24 hours. CHR2797 inhibited anti-apoptotic protein Mcl-1 in MM1R and U266 MM cells.Clinical Trials [2]:PatientsPatients With Acute Myeloid Leukemia and MyelodysplasiaDosage form60 mg to 180 mg, 28 days, capsules, orally after food each dayApplicationOral once daily dosing with 130 mg tosedostat was well tolerated and had significant antileukemic activity.Other notesPlease test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.References:[1]. Acharya C, Zhong M Y, Tannenbaum D, et al. Targeting Aminopeptidases by Tosedostat (TST)(CHR2797), Alone and with LBH589, Induces Significant Cytotoxicity Against Human Multiple Myeloma (MM) Cells[J]. 2012.[2]. Lwenberg B, Morgan G, Ossenkoppele G J, et al. Phase I/II clinical study of Tosedostat, an inhibitor of aminopeptidases, in patients with acute myeloid leukemia and myelodysplasia[J]. Journal of Clinical Oncology, 2010, 28(28): 4333-4338.Tosedostat (CHR2797) Dilution CalculatorConcentration (start)xVolume (start)=Concentration (final)xVolume (final) femtomolar picomolar nanomolar micromolar millimolar molar nanoliter microliter milliliter liter femtomolar picomolar nanomolar micromolar millimolar molar microliter milliliter liter C1V1C2V2calculateTosedostat (CHR2797) Molarity CalculatorMass=ConcentrationxVolumexMW* picograms nanograms micrograms milligrams grams kilograms femtomolar picomolar nanomolar micromolar millimolar molar nanoliter microliter milliliter liter g/molcalculate Chemical Properties Cas No. 238750-77-1SDF Download SDF Chemical Name cyclopentyl (2S)-2-[[(2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoyl]amino]-2-phenylacetate Canonical SMILES CC(C)CC(C(C(=O)NO)O)C(=O)NC(C1=CC=CC=C1)C(=O)OC2CCCC2 Formula C21H30N2O6 M.Wt 406.47 Solubility ≥40.6 mg/mL in DMSO, ≥15.07 mg/mL in EtOH with ultrasonic, Storage Store at -20°CShipping ConditionEvaluation sample solution : ship with blue ice.All other available size:ship with RT , or blue ice upon requestGeneral tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. BackgroundTosedostat is a novel and potent oral aminopeptidase inhibitor with clinical activity in a previous phase 1–2 study in elderly patients with relapsed or refractory acute myeloid leukaemia (AML). [2]Aminopeptidases play a key role in the protein cell cycle. Inhibition of aminopeptidase results in the amino acid deprivation response, which occurs selectively in transformed cells and leads to upregulation of proapoptotic factors including CHOP and NOXA, activation of stress-related pathways such as NFκB, and inhibition of mTOR, which switches off protein synthesis. [2]Tosedostat (CHR-2797) is converted intracellularly into a pharmacologically active metabolite CHR-79888. [1]Tosedostat has antiproliferative, antiangiogenic and proapoptotic effects. Tosedostat is currently in a clinical trial phase for anticancer therapy, and displayed a broad antifungal activity against different Candida spp, including Candida glabrata. Tosedostat depletes sensitive tumour cells of amino acids by blocking protein recycling and thereby generates an antiproliferative effect. Tosedostat has activity in older patients with relapsed or refractory AML. [2]References:1.Van Herpen CM, Eskens FA, de Jonge M et al. A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours. Br J Cancer. 2010 Oct 26;103(9):1362-8. 2.Cortes J, Feldman E, Yee K et al. Two dosing regimens of tosedostat in elderly patients with relapsed or refractory acute myeloid leukaemia (OPAL): a randomised open-label phase 2 study. Lancet Oncol. 2013 Apr;14(4):354-62.