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.
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 |
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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。 |
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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 |
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工作液浓度: mg/ml;
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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。
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Quality Control & SDS
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- Purity: >98.00%
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