STF-083010 is a specific IRE1α inhibitor. STF-083010 inhibits Ire1 endonuclease activity, without affecting its kinase activity, after endoplasmic reticulum stress.

Ire1^[1]

STF-083010 shows cytostatic and cytotoxic activity in a dose- and time-dependent manner. Treatment with STF-083010 shows significant antimyeloma activity in model human multiple myeloma (MM) xenografts. RPMI 8226 human MM cells grown as tumor xenografts are treated in NSG mice. Intraperitoneal injection of STF-083010 alone (day 1, day 8) significantly inhibits the growth of these tumors^[1]. STF-083010 is an IRE1α-specific inhibitor. Four pancreatic cancer cell lines (Panc0403, Panc1005, BxPc3, MiaPaCa2) are treated with different combination of Bortezomib (10 or 50 nM) and STF (10 or 50 μM). The normalized isobologram analysis demonstrates synergistic activity between 10 μM STF and either 10 or 50 nM bortezomib in all four cell lines. Moreover, a higher concentration of STF (50 μM) attains synergy after addition of bortezomib either at a concentration of 10 nM when tested against BxPc3 cells, at a concentration of 50 nM against Panc1005 cells, and at either 10 or 50 nM against Panc0403 cells^[2]. STF-083010 (50 μM) suppresses the growth of p53-deficient human cancer cells^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Treatment with STF-083010 reduces the viability of HCT116 p53^-/- cells by approximately 20% compared with that of HCT116 p53^-/-cells. Administration of STF-083010 to tumors induced by HCT116 p53^-/- cells significantly reduces tumor volume and weight by 75% and 73% at the endpoint, respectively^[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

317.38

C₁₅H₁₁NO₃S₂

307543-71-1

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : 100 mg/mL (315.08 mM; Need ultrasonic)

*

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, 6 months; -20°C, 1 month。-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。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 3.25 mg/mL (10.24 mM); Clear solution

  此方案可获得 ≥ 3.25 mg/mL (10.24 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 32.5 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• [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.

  [2]. Chien W, et al. Selective inhibition of unfolded protein response induces apoptosis in pancreatic cancer cells. Oncotarget. 2014 Jul 15;5(13):4881-94.

  [3]. Namba T, et al. Loss of p53 enhances the function of the endoplasmic reticulum through activation of the IRE1α/XBP1 pathway. Oncotarget. 2015 Aug 21;6(24):19990-20001.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

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).

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [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.

  [2]. Chien W, et al. Selective inhibition of unfolded protein response induces apoptosis in pancreatic cancer cells. Oncotarget. 2014 Jul 15;5(13):4881-94.

  [3]. Namba T, et al. Loss of p53 enhances the function of the endoplasmic reticulum through activation of the IRE1α/XBP1 pathway. Oncotarget. 2015 Aug 21;6(24):19990-20001.