Tosedostat (Synonyms: CHR-2797)

Name: Tosedostat
Brand: MedChemExpress
SKU: HY-14807
Rating: 5.0 (7 reviews)

Cat. No.: HY-14807 Purity: 99.75%: FAQs
Data Sheet SDS COA Handling Instructions

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Tosedostat (CHR-2797) is an orally active aminopeptidase inhibitor. CHR-2797 exerts antiproliferative effects against a range of tumor cell lines.

For research use only. We do not sell to patients.

Tosedostat Chemical Structure

CAS No. : 238750-77-1

Size	Price	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 181	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 181	In-stock	Estimated Time of Arrival: December 31
Solid
1 mg	USD 78	In-stock	Estimated Time of Arrival: December 31
5 mg	USD 165	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 250	In-stock	Estimated Time of Arrival: December 31
25 mg	USD 450	In-stock	Estimated Time of Arrival: December 31
50 mg	USD 675	In-stock	Estimated Time of Arrival: December 31
100 mg	USD 1010	In-stock	Estimated Time of Arrival: December 31
200 mg		Get quote
500 mg		Get quote

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Based on 7 publication(s) in Google Scholar

Other Forms of Tosedostat:

Tosedostat-d5 Get quote

7 Publications Citing Use of MCE Tosedostat

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Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

Tosedostat (CHR-2797) is an orally active aminopeptidase inhibitor. CHR-2797 exerts antiproliferative effects against a range of tumor cell lines^[1].

IC₅₀ & Target

Aminopeptidase^[1]

Cellular Effect

Cell Line	Type	Value	Description	References
HL-60	EC₅₀	4.7 μM Compound: 3	Antiproliferative activity against human HL60 cells after 72 hrs by MTT assay Antiproliferative activity against human HL60 cells after 72 hrs by MTT assay	[PMID: 28803047]
MOLT-4	EC₅₀	2.1 μM Compound: 3	Antiproliferative activity against human MOLT4 cells after 72 hrs by MTT assay Antiproliferative activity against human MOLT4 cells after 72 hrs by MTT assay	[PMID: 28803047]
Vero	CC₅₀	13 μM Compound: 3	Cytotoxicity against African green monkey Vero cells assessed as reduction in cell proliferation after 72 hrs by MTT assay Cytotoxicity against African green monkey Vero cells assessed as reduction in cell proliferation after 72 hrs by MTT assay	[PMID: 28803047]

In Vitro

Treatment of HL-60 cells with Tosedostat (CHR-2797) leads to an increase in the secretion of Stanniocalcin 2 (STC2) protein into the growth medium. Increases in SLC7A11 expression are detectable at 60 nM Tosedostat and as early as 2 h posttreatment. The IC₅₀s for inhibition of proliferation by Tosedostat in U-937 and HuT 78 cell lines are 10 nM and >10 μM, respectively. Tosedostat treatment increases expression of amino acid deprivation response (AADR) genes in U-937 cells but not in HuT 78 cells^[1]. By 24 h with 0.01 μM Tosedostat 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^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Tosedostat (CHR-2797) is active as an anticancer agent in vivo in rodent cancer models, 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 treatment^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

Molecular Weight

406.47

Formula

C₂₁H₃₀N₂O₆

CAS No.

238750-77-1

Appearance

Solid

Color

White to off-white

SMILES

O=C(OC1CCCC1)[C@@H](NC([C@@H]([C@H](O)C(NO)=O)CC(C)C)=O)C2=CC=CC=C2

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Solvent & Solubility

In Vitro:

DMSO : 25 mg/mL (61.51 mM; Need ultrasonic and warming; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.4602 mL	12.3010 mL	24.6021 mL
5 mM	0.4920 mL	2.4602 mL	4.9204 mL
10 mM	0.2460 mL	1.2301 mL	2.4602 mL

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (6.15 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (6.15 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (6.15 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.

Purity & Documentation

Purity: 99.75%

Select Batch:

Data Sheet (281 KB) SDS (393 KB)

COA (249 KB) LCMS (105 KB)

Handling Instructions (2659 KB)

References

[1]. Emma M Smith, et al. The combination of HDAC and aminopeptidase inhibitors is highly synergistic in myeloma and leads to disruption of the NFκB signalling pathway. Oncotarget. 2015 Jul 10;6(19):17314-27. [Content Brief]

[2]. Krige D, et al. CHR-2797: an antiproliferative aminopeptidase inhibitor that leads to amino acid deprivation in human leukemic cells. Cancer Res. 2008 Aug 15;68(16):6669-79. [Content Brief]

[3]. Jenkins C, et al. Aminopeptidase inhibition by the novel agent CHR-2797 (tosedostat) for the therapy of acute myeloid leukemia. Leuk Res. 2011 May;35(5):677-81. [Content Brief]

[4]. Smith EM, et al. The combination of HDAC and aminopeptidase inhibitors is highly synergistic in myeloma and leads to disruption of the NFκB signalling pathway. Oncotarget. 2015 Jul 10;6(19):17314-27.

Kinase Assay ^[1]	Cells are seeded at a density of 4×10⁴/mL, cultured for 24 h, then treated with 0.06 to 6 μM Tosedostat (CHR-2797) for 24 h. After treatment, 5×10⁴ cells are washed with PBS and seeded in 100 μL Cys/Met-free RPMI 1640 containing Tosedostat, supplemented with 10% dialyzed FBS. 1.5 μCi [³⁵S]Cys/Met (>1,000 Ci/mmol) is added, and incubation continued for 1 h at 37°C. Cells are captured onto 96-well GF/B filter plates and washed twice with PBS before precipitation with 10% ice-cold trichloroacetic acid (TCA) for 1 h at 4°C. Precipitated proteins are washed four times with ice-cold 10% TCA and air-dried for 1 h. UltimaGold scintillation cocktail is added and allowed to mix for 1 h before scintillation counting using a scintillation counter^[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay ^[2]	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)^[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[3]	A breeding colony of NOD/SCID IL2R gamma^null 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 Matrigel^TM 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^[3]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[1]. Emma M Smith, et al. The combination of HDAC and aminopeptidase inhibitors is highly synergistic in myeloma and leads to disruption of the NFκB signalling pathway. Oncotarget. 2015 Jul 10;6(19):17314-27. [Content Brief] [2]. Krige D, et al. CHR-2797: an antiproliferative aminopeptidase inhibitor that leads to amino acid deprivation in human leukemic cells. Cancer Res. 2008 Aug 15;68(16):6669-79. [Content Brief] [3]. Jenkins C, et al. Aminopeptidase inhibition by the novel agent CHR-2797 (tosedostat) for the therapy of acute myeloid leukemia. Leuk Res. 2011 May;35(5):677-81. [Content Brief] [4]. Smith EM, et al. The combination of HDAC and aminopeptidase inhibitors is highly synergistic in myeloma and leads to disruption of the NFκB signalling pathway. Oncotarget. 2015 Jul 10;6(19):17314-27.

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

DMSO	1 mM	2.4602 mL	12.3010 mL	24.6021 mL	61.5052 mL
	5 mM	0.4920 mL	2.4602 mL	4.9204 mL	12.3010 mL
	10 mM	0.2460 mL	1.2301 mL	2.4602 mL	6.1505 mL
	15 mM	0.1640 mL	0.8201 mL	1.6401 mL	4.1003 mL
	20 mM	0.1230 mL	0.6151 mL	1.2301 mL	3.0753 mL
	25 mM	0.0984 mL	0.4920 mL	0.9841 mL	2.4602 mL
	30 mM	0.0820 mL	0.4100 mL	0.8201 mL	2.0502 mL
	40 mM	0.0615 mL	0.3075 mL	0.6151 mL	1.5376 mL
	50 mM	0.0492 mL	0.2460 mL	0.4920 mL	1.2301 mL
	60 mM	0.0410 mL	0.2050 mL	0.4100 mL	1.0251 mL

Tosedostat Related Classifications

Cancer

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

Tosedostat238750-77-1CHR-2797CHR2797CHR 2797AminopeptidaseInhibitorinhibitorinhibit

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Tosedostat (Synonyms: CHR-2797)

Customer Review

Other Forms of Tosedostat:

Tosedostat Related Antibodies

7 Publications Citing Use of MCE Tosedostat

Featured Recommendations

•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

Biological Activity

Protocol

Purity & Documentation

References

Customer Review

Tosedostat Related Antibodies

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Dilution Calculator

Complete Stock Solution Preparation Table

Tosedostat Related Classifications

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