GSK 2830371 is a highly selectiveWip1phosphataseinhibitor withIC₅₀of 6 nM.

IC50: 6 nM (Wip1 phosphatase)^[1]

GSK 2830371 potently inhibits Wip1 (2-420) dephosphorylation of FDP and the endogenous substrates phospho-p38 MAPK (T180) with IC₅₀values of 6 nM and 13 nM, respectively. In thePPM1D-amplified MCF7 breast carcinoma cells, treatment with GSK 2830371 (0.04, 0.11, 0.33, 1, 3, and 9 μM) increased phosphorylation of substrates in a concentration-dependent manner. Treatment of MX-1 and MCF7 cells (Wip1amplified, p53 wild type) with GSK 2830371 (0.001, 0.01, 0.1, 1, and 10 μM) causes concentration-dependent effects in cell growth assays^[1]. GSK2830371 has a 50% growth inhibitory concentration (GI₅₀) of 2.65 μM±0.54 (SEM) in MCF-7 cells. Treatment of MCF-7 cells with 2.5μM GSK2830371 results in marked time-dependent degradation of both isoforms of WIP1 over 8 hours which correlated with p53 stabilisation and phospho-p53^Ser15(pp53^Ser15)^[2].

In a pharmacodynamic assay, orally administered GSK 2830371 increases phosphorylation of Chk2 (T68) and p53 (S15) and decreased Wip1protein concentrations in DOHH2 tumors. Following 14 d of oral dosing at 150 mg per kg body weight, BID (twice daily) and TID (thrice daily), GSK 2830371 inhibits the growth of DOHH2 tumor xenografts by 41% and 68%, respectively. Comparable tumor growth inhibition is observed in mice treated BID with either 75 or 150 mg per kg body weight. Greater tumor growth inhibition with the TID schedule is consistent with a short half-life of GSK 2830371 in mice and suggests that sustained inhibition of Wip1 may be required for maximal antitumor effect^[1].

461.02

Solid

C₂₃H₂₉ClN₄O₂S

1404456-53-6

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 51 mg/mL(110.62 mM)

*"≥" means soluble, but saturation unknown.

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℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 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： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 2.5 mg/mL (5.42 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.42 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
• 2.

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

  Solubility: 2.5 mg/mL (5.42 mM); Suspended solution; Need ultrasonic

  此方案可获得 2.5 mg/mL (5.42 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

  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 μL20% 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
• 3.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 2.5 mg/mL (5.42 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.42 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。