PF-3758309 (PF-03758309) 是一种有效的、口服的、可逆的 ATP 竞争性PAK4抑制剂 (Kd= 2.7 nM;Ki=18.7 nM)。PF-3758309 具有 PAK4 抑制剂的预期细胞功能:抑制锚定独立生长、诱导凋亡、细胞骨架重塑和抑制增殖。
生物活性 | PF-3758309 (PF-03758309) is a potent, orally available, and reversible ATP-competitive inhibitor ofPAK4(Kd= 2.7 nM;Ki=18.7 nM). PF-3758309 has the expected cellular functions of aPAK4inhibitor: inhibition of anchorage-independent growth, induction ofapoptosis, cytoskeletal remodeling, and inhibition of proliferation[1][2][3]. |
IC50& Target[1] | PAK4 18.7 nM (Ki) | PAK1 13.7 nM (Ki) | PAK5 18.1 nM (Ki) | PAK6 17.1 nM (Ki) | PAK2 190 nM (IC50) | PAK3 99 nM (IC50) | PAK4 2.7 nM (Kd) |
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体外研究 (In Vitro) | PF-3758309 has similar enzymatic potency against the kinase domains of the other group B PAKs (PAK5, Ki=18.1 nM; PAK6, Ki=17.1 nM) and group A PAK1 (Ki=13.7 nM), but is less active against the other two group A PAKs (PAK2, IC50=190 nM; PAK3, IC50=99 nM)[1]. In cells, PF-3758309 inhibits phosphorylation of the PAK4 substrate GEF-H1 (IC50=1.3 nM) and anchorage-independent growth of a panel of tumor cell lines (IC50=4.7 nM)[1]. PF-3758309 also inhibits endogenous pGEF-H1 accumulation in HCT116 cells. PF-3758309 potently inhibits cellular proliferation (IC50=20 nM) and anchorage-independent growth (IC50=27 nM) of A549 cells[1].
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体内研究 (In Vivo) | PF-3758309 (7.5-30 mg/kg; p.o.; twice daily for 9-18 days) results in statistically significant tumor growth inhibition (TGI) in HCT116 and A549 models[1].
Animal Model: | Female nu/nu, CRL breed 6–8 weeks old mice (bearing HCT116 and A549 tumors)[1] | Dosage: | 7.5-30 mg/kg | Administration: | Oral administration; twice daily for 9-18 days | Result: | Significant tumor growth inhibition (TGI) in HCT116 and A549 models. |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | Powder | -20°C | 3 years | | 4°C | 2 years | In solvent | -80°C | 6 months | | -20°C | 1 month |
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溶解性数据 | In Vitro: DMSO : ≥ 100 mg/mL(203.82 mM) *"≥" means soluble, but saturation unknown. 配制储备液 1 mM | 2.0382 mL | 10.1912 mL | 20.3824 mL | 5 mM | 0.4076 mL | 2.0382 mL | 4.0765 mL | 10 mM | 0.2038 mL | 1.0191 mL | 2.0382 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℃, 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。 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 (5.10 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.10 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。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (5.10 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.10 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 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (5.10 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.10 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本网站选购。
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