G-5555

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

G-5555  纯度: 99.29%

G-5555 是有效 PAK1 抑制剂,对 PAK1 和 PAK2 的 Ki 值分别为 3.7 nM 和 11 nM。

G-5555

G-5555 Chemical Structure

CAS No. : 1648863-90-4

规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ¥1190 In-stock
5 mg ¥1100 In-stock
10 mg ¥1600 In-stock
25 mg ¥3600 In-stock
50 mg ¥6400 In-stock
100 mg ¥11000 In-stock
200 mg   询价  
500 mg   询价  

* Please select Quantity before adding items.

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生物活性

G-5555 is a potent p21-activated kinase 1 (PAK1) inhibitor with Kis of 3.7 nM and 11 nM for PAK1 and PAK2, respectively.

IC50 & Target[2]

PAK1

3.7 nM (Ki)

PAK2

11 nM (Ki)

体外研究
(In Vitro)

G-5555 is a potent PAK1 inhibitor with a Ki of 3.7 nM. G-5555 shows excellent kinase selectivity and inhibits only eight out of the 235 kinases tested other than PAK1 with inhibition >70%: PAK2, PAK3, KHS1, Lck, MST3, MST4, SIK2, and YSK1. The IC50s of G-5555 against SIK2, PAK2, KHS1, MST4, YSK1, MST3 and Lck are 9, 11, 10, 20, 34, 43, 52 nM, respectively. In general, G-5555 demonstrates high selectivity for the group I PAKs. There is negligible activity for G-5555 against the hERG channel with IC50 more than 10 μM in a patch clamp assay[1]. G-5555 potently inhibits PAK2, with a Ki of 11 nM. In an array of 23 breast cancer cell lines, G-5555 has significantly greater growth inhibitory activity in cell lines that are PAK-amplified compared to non-amplified lines[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.

体内研究
(In Vivo)

G-5555 exhibits low blood clearance and an acceptable half-life. Good oral exposure (AUC = 30 μM•h) and high oral bioavailability (F = 80%) are achieved[1]. In an H292 non-small cell lunger cancer (NSCLC) xenograft study in mice, G-5555 inhibits phosphorylation of the PAK1/2 downstream substrate mitogen-activated protein kinase 1 (MEK1) S298 and, when administered at an oral dose of 25 mg/kg b.i.d., imparts 60% tumor growth inhibition in this model13 and a PAK1 amplified breast cancer xenograft model, MDAMB-175[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.

分子量

492.96

Formula

C25H25ClN6O3

CAS 号

1648863-90-4

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

溶解性数据
In Vitro: 

DMSO : 25 mg/mL (50.71 mM; ultrasonic and warming and heat to 80°C)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.0286 mL 10.1428 mL 20.2856 mL
5 mM 0.4057 mL 2.0286 mL 4.0571 mL
10 mM 0.2029 mL 1.0143 mL 2.0286 mL

*

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 (sealed storage, away from moisture)。-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: ≥ 2.5 mg/mL (5.07 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.07 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-CD in saline)

    Solubility: ≥ 2.5 mg/mL (5.07 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.07 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
  • 3.

    请依序添加每种溶剂: 10% DMSO    90% corn oil

    Solubility: ≥ 2.5 mg/mL (5.07 mM); Clear solution

    此方案可获得 ≥ 2.5 mg/mL (5.07 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。

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
  • [1]. Ndubaku CO, et al. Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pK a Polar Moiety. ACS Med Chem Lett. 2015 Oct 31;6(12):1241-6.

    [2]. Rudolph J, et al. Chemically Diverse Group I p21-Activated Kinase (PAK) Inhibitors Impart Acute Cardiovascular Toxicity with a Narrow Therapeutic Window. J Med Chem. 2016 Jun 9;59(11):5520-41.

Kinase Assay
[1]

The 10 µL assay mixtures contain 50 mM HEPES (pH 7.5), 0.01% Brij-35, 10 mM MgCl2, 1 mM EGTA, 2 µM FRET peptide substrate, and PAK enzyme (20 pM PAK1; 50 pM PAK2; 90 pM PAK4). Incubations are carried out at 22°C in black polypropylene 384-well plates. Prior to the assay, enzyme, FRET peptide substrate and serially diluted test compounds (G-5555, etc.) are preincubated together in assay buffer (7.5 µL) for 10 minutes, and the assay is initiated by the addition of 2.5 µL assay buffer containing 4× ATP (160 µM PAK1; 480 µM PAK2; 16 µM PAK4). Following the 60-minute incubation, the assay mixtures are quenched by the addition of development reagent, and 1 hour later the emissions of Coumarin (445 nm) and Fluorescein (520 nm) are determined after excitation at 400 nm[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.

Animal Administration
[1]

Mice[1]
Three mice in each of the two groups are administered 25 mg/kg oral suspension dose twice, with the second dose given 6 hours after the first dose. The dose volumes are 5 mL/kg for the IV group and 10 mL/kg for the PO groups. Following administration of G-5555, 15 µL of blood is collected at each time point are stored at -70 to -80°C until analysis[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.

参考文献
  • [1]. Ndubaku CO, et al. Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pK a Polar Moiety. ACS Med Chem Lett. 2015 Oct 31;6(12):1241-6.

    [2]. Rudolph J, et al. Chemically Diverse Group I p21-Activated Kinase (PAK) Inhibitors Impart Acute Cardiovascular Toxicity with a Narrow Therapeutic Window. J Med Chem. 2016 Jun 9;59(11):5520-41.

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