SKF-96365 hydrochloride is a potent TRP channel blocker and a store-operated Ca²⁺ entry (SOCE) inhibitor. SKF-96365 hydrochloride significantly inhibits hERG, hKCNQ1/hKCNE1, hKir2.1 and hKv4.3 current, and significantly prolongs the QTc interval in isolated guinea pig hearts. SKF-96365 hydrochloride exhibits potent anti-neoplastic activity by inducing cell-cycle arrest and apoptosis in colorectal cancer cells^[1][2].

SKF-96365 exhibits potent anti-neoplastic activity by inducing cell-cycle arrest and apoptosis in colorectal cancer cells. SKF-96365 inhibits hERG current in a concentration-dependent manner^[1]. SKF-96365 can induces cytoprotective autophagy to delay apoptosis by preventing the release of cytochrome c (cyt c) from the mitochondria into the cytoplasm. Mechanistically, SKF-96365 treatment inhibits the calcium/calmodulin-dependent protein kinase IIγ (CaMKIIγ)/AKT signaling cascade. Overexpression of CaMKIIγ or AKT abolishes the effects of SKF-96365 on cancer cells, suggesting a critical role of the CaMKIIγ/AKT signaling pathway in SFK-96365-induced biological effects^[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.

SKF-96365 inhibits CRC cell growth in vivo. SKF-96365 treatment results in a decrease of p-CaMKII and p-AKT as well as an increase in LC3-II, cleaved PARP, caspase-3, and caspase-9 in mice^[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.

402.91

C₂₂H₂₇ClN₂O₃

130495-35-1

Room temperature in continental US; may vary elsewhere.

4°C, protect from light, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

H₂O : 100 mg/mL (248.19 mM; Need ultrasonic)

DMSO : 100 mg/mL (248.19 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 (protect from light, stored under nitrogen)。-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。

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： Saline

  Solubility: 100 mg/mL (248.19 mM); Clear solution; Need ultrasonic
• 2.

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

  Solubility: ≥ 2.5 mg/mL (6.20 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.20 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 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

• 3.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.5 mg/mL (6.20 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.20 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 4.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (6.20 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.20 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Liu H, et al. SKF-96365 blocks human ether-à-go-go-related gene potassium channels stably expressed in HEK 293 cells. Pharmacological Research. Pharmacol Res, 2016 Feb, 104:61-9.

  [2]. Jing Z, et al. SKF-96365 activates cytoprotective autophagy to delay apoptosis in colorectal cancer cells through inhibition of the calcium/CaMKIIγ/AKT-mediated pathway. Cancer Lett, 2016 Mar 28, 372(2):226-38.

Mice: Five to six-week-old female athymic BALB/c mice are inoculated into the right oxter with HCT116 cells. When the diameter of the subcutaneous tumor reaches approximately 0.5 cm, animals are randomLy assigned to the vehicle, SKF-96365 alone, HCQ alone or SKF-96365+HCQ. SKF-96365 is applied (20 mg/kg) and HCQ is applied (60 mg/kg) daily for 14 successive days by i.p. injection. Tumor sizes and volume are determined. Eight mice are included in each group. Mice are sacrificed 24 h after the last treatment. The tumors are weighed and processed for western blot analysis or paraffin embedding^[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]. Liu H, et al. SKF-96365 blocks human ether-à-go-go-related gene potassium channels stably expressed in HEK 293 cells. Pharmacological Research. Pharmacol Res, 2016 Feb, 104:61-9.

  [2]. Jing Z, et al. SKF-96365 activates cytoprotective autophagy to delay apoptosis in colorectal cancer cells through inhibition of the calcium/CaMKIIγ/AKT-mediated pathway. Cancer Lett, 2016 Mar 28, 372(2):226-38.