Tosedostat (CHR2797)
(Synonyms: 托舍多特,CHR-2797) 目录号 : GC10406
An aminopeptidase inhibitor
Cas No.:238750-77-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
| Cell experiment [1]: | |
|
Cell lines |
Human multiple myeloma (MM) cells |
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Preparation method |
The 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 condition |
10 μM, 72 hours |
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Applications |
CHR2797 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]: | |
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Patients |
Patients With Acute Myeloid Leukemia and Myelodysplasia |
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Dosage form |
60 mg to 180 mg, 28 days, capsules, orally after food each day |
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Application |
Oral once daily dosing with 130 mg tosedostat was well tolerated and had significant antileukemic activity. |
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Other notes |
Please 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. |
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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 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.
| Cas No. | 238750-77-1 | SDF | |
| 别名 | 托舍多特,CHR-2797 | ||
| 化学名 | 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 | ||
| 分子式 | C21H30N2O6 | 分子量 | 406.47 |
| 溶解度 | ≥ 40.6 mg/mL in DMSO, ≥ 15.07 mg/mL in EtOH with ultrasonic | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.4602 mL | 12.301 mL | 24.6021 mL |
| 5 mM | 0.492 mL | 2.4602 mL | 4.9204 mL |
| 10 mM | 0.246 mL | 1.2301 mL | 2.4602 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。