SecinH3 is an antagonist of cytohesins with IC₅₀s of 5.4 μM, 2.4 μM, 5.4 μM, 5.6 μM, 5.6 μM and 65 μM for hCyh1, hCyh2, mCyh3, hCyh3, drosophila steppke and yGea2-S7, respectively.

IC50: 5.4 μM (hCyh1)，2.4 μM (hCyh2)，5.4 μM (mCyh3)，5.6 μM (hCyh3)，5.6 μM (drosophila steppke), 65 μM (yGea2-S7)^[1]

SecinH3 is a Sec7-specific guanine nucleotide exchange factor (GEF) inhibitor with preference for the small GEFs of the cytohesin family. SecinH3 almost completely blocks the insulin-dependent transcriptional repression of IGFBP1 with an IC₅₀ of 2.2 μM. Insulin-stimulated translocation of ARF6 to the plasma membrane is also inhibited by SecinH3. It is found that SecinH3 inhibits the insulin-dependent phosphorylation of Akt and FoxO1A in a concentration-dependent manner. Insulin-induced exclusion of FoxO1A from the nucleus is completely prevented by SecinH3. The binding of IRS1 to the insulin receptor is also inhibited by SecinH3^[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.

Compare to mice fed the same chow without SecinH3, the expression levels of the insulin-repressed gluconeogenic genes are elevated, whereas the insulin-induced glycolytic genes are reduced in SecinH3-treated mice. Insulin-stimulated Akt phosphorylation is also inhibited in SecinH3-treated mice. The expression of the genes for two key enzymes of mitochondrial β-oxidation, carnitine palmitoyltransferase 1a (Cpt1a) and hydroxyacyl-CoA dehydrogenase (Hadha), both of which are repressed by insulin, is increased in the SecinH3-treated mice. It is found significantly increased levels of serum insulin with slightly elevated glucose concentrations in SecinH3-treated mice. Accordingly, 3-hydoxybutyrate is increased in the serum of SecinH3-treated mice^[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.

460.51

C₂₄H₂₀N₄O₄S

853625-60-2

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 : 130 mg/mL (282.30 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    90% corn oil

  Solubility: ≥ 3.25 mg/mL (7.06 mM); Clear solution

  此方案可获得 ≥ 3.25 mg/mL (7.06 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 32.5 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Hafner M, et al. Inhibition of cytohesins by SecinH3 leads to hepatic insulin resistance. Nature. 2006 Dec 14;444(7121):941-4.

10⁵ HepG2 cells are seeded in 12 well plates and cultured for 24 h in EMEM containing 10 % FCS. Cells are then serum starved in EMEM for 24 h and stimulated for 12 h with 10 nM insulin in the presence of SecinH3, the negative control D5 or vehicle (0.2% final concentration of DMSO). Total mRNA is prepared using Kit and cDNA for qPCR is generated from 1 μg RNA. qPCR is performed and data are normalized to β₂-microglobulin expression^[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.

C57/Bl6N mice are kept on a 12 h light/dark cycle in a pathogen-free animal facility and fed ad libitum with standard mice diet. After feeding with standard diet or with the same diet containing 0.9 μmol/g SecinH3 for 3 days, mice are intraperitoneally injected with 100 μL saline containing or not 40 μg recombinant human insulin. After 10 min the mice are anaesthetized and the liver is removed and lysed in lysis buffer. Normalized amounts of protein are either separated by SDS-PAGE and transferred onto nitrocellulose, or immunoprecipitated using agarose-conjugated antibodies against IRβ or IRS1^[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.

• [1]. Hafner M, et al. Inhibition of cytohesins by SecinH3 leads to hepatic insulin resistance. Nature. 2006 Dec 14;444(7121):941-4.