STF 083010
(Synonyms: IRE1 Inhibitor I) 目录号 : GC12937
An inhibitor of IRE1 endonuclease activity
Cas No.:307543-71-1
Sample solution is provided at 25 µL, 10mM.
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IC50: N/A
STF 083010 is an inhibitor of IRE1α endonuclease activity, and does not alter IRE1α kinase.
In vitro: After endoplasmic reticulum stress both in vitro and in vivo, STF-083010 prevented Ire1 endonuclease activity without affecting its kinase activity. Treatment with STF-083010 exhibited significant antimyeloma activity in model human MM xenografts. Similarly, compared with other similarly isolated cell populations, STF-083010 was preferentially toxic to freshly isolated human CD138 MM cells. On basis of the identification of this novel Ire1 inhibitor, propose that the Ire1-XBP1 axis is a promising target for anticancer therapy (especially in the context of MM) [1].
In stark contrast, when apoptosis of tumor cells desired, therapeutic strategies attempted to stimulate ER stress with the aim of killing cancerous cells in the case of cancer treatment. For example, it enhanced the killing of these cancer cells that exposure of human multiple myeloma cells to STF083010, and that or treatment of a human pancreatic cancer cell line with bortezomib, [2].
In vivo: The small molecule STF083010, identified by a high-throughput screen of compounds affecting IRE1 activity, was capable of directly inhibiting the endonuclease function of IRE1 without affecting its kinase activity. After treatment of mice harboring subcutaneous xenografts led to tumor shrinkage and multiple myeloma cells harvested from cancer patients died following exposure to STF083010, the antimyeloma therapeutic potential of STF083010 was convincingly demonstrated [2].
Clinical trial: So far, no clinical study has been conducted.
References:
[1]. Papandreou I, Denko NC, Olson M, Van Melckebeke H, Lust S, Tam A, Solow-Cordero DE, Bouley DM, Offner F, Niwa M, Koong AC. Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma. Blood. 2011 Jan 27; 117 (4):1311-4.
[2]. Kraskiewicz H, FitzGerald U. InterfERing with endoplasmic reticulum stress. Trends Pharmacol Sci. 2012 Feb; 33 (2):53-63.
Kinase experiment: | The hIre1α protein, containing both Ire1 cytoplasmic kinase and RNase domains, is expressed and purified from baculovirus. Autophosphorylation activity is determined by the addition of 32P-γATP. Endonuclease activity is determined by the addition of radiolabeled HAC1 508-nt RNA substrate synthesized in vitro using α 32P-UTP. STF083010 is incubated with recombinant hIRE1α protein, radiolabeled HAC1 508 nt RNA, and appropriate buffers. Kinase activity and RNAse cleavage products are quantitated by polyacrylamide gel electrophoresis and 32P-γATP or 32P-UTP autoradiography, respectively[1]. |
Cell experiment: | Cell viability is determined using the MTT method. After treatment with Tunicamycin (Tm), STF-083010 (50 μM), or both, cells are incubated with MTT solution (1 mg/mL) for 2 h. Isopropanol and HCl are added to the final concentrations of 50% and 20 mM, respectively. The optical density at 570 nm is determined using a spectrophotometer using a reference wavelength of 630 nm[3]. |
Animal experiment: | Mice[3]Each BALB/c nude mouse (male, 5 weeks of age) is subcutaneously inoculated in the right and left hind footpads with 5×106 HCT116 p53+/+ or HCT116 p53-/- cells. Four days later, DMSO or STF-083010 (40 mg/kg) is intraperitoneally administrated every 3 days. Tumors are measured every 5 days, and their volumes are calculated using the equation mm3=(length (mm))×(width (mm))2/2). |
References: [1]. Papandreou I, et al. Identification of an Ire1alpha endonuclease specific inhibitor with cytotoxic activity against human multiple myeloma. Blood. 2011 Jan 27;117(4):1311-4. | |
| Cas No. | 307543-71-1 | SDF | |
| 别名 | IRE1 Inhibitor I | ||
| 化学名 | (Z)-N-((2-oxonaphthalen-1(2H)-ylidene)methyl)thiophene-2-sulfonamide | ||
| Canonical SMILES | O=S(N/C=C1C2=CC=CC=C2C=CC/1=O)(C3=CC=CS3)=O | ||
| 分子式 | C15H11NO3S2 | 分子量 | 317.38 |
| 溶解度 | ≥ 31.7mg/mL in DMSO | 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.1508 mL | 15.754 mL | 31.508 mL |
| 5 mM | 0.6302 mL | 3.1508 mL | 6.3016 mL |
| 10 mM | 0.3151 mL | 1.5754 mL | 3.1508 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。
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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