| 规格 | 价格 | 库存 | 数量 |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
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| 体外研究 (In Vitro) |
与其他 B 组 PAK（PAK5，Ki=18.1 nM；PAK6，Ki=17.1 nM）和 A 组 PAK1（Ki=13.7 nM）的激酶结构域相比，PF-3758309 表现出相当的酶效力。然而，它对其他两种 A 组 PAK（PAK2，IC50=190 nM；PAK3，IC50=99 nM）表现出较低的活性[1]。 PF-3758309 抑制一组不依赖贴壁的肿瘤细胞系的生长 (IC50=4.7 nM) 以及细胞中 PAK4 底物 GEF-H1 的磷酸化 (IC50=1.3 nM)[1]。此外，PF-3758309 还可防止 HCT116 细胞积累内源性 pGEF-H1。 PF-3758309 显着抑制 A549 细胞的贴壁依赖性生长 (IC50=27 nM) 和增殖 (IC50=20 nM)[1]。
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| 体内研究 (In Vivo) |
在 HCT116 和 A549 模型中，PF-3758309（7.5-30 mg/kg；口服；每天两次，持续 9-18 天）可产生统计学上显着的肿瘤生长抑制 (TGI)[1]。
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| 动物实验 |
Animal/Disease Models: Female nu/nu, CRL breed 6–8 weeks old mice (bearing HCT116 and A549 tumors)[1]
Doses: 7.5-30 mg/kg Route of Administration: Oral administration; twice (two times) daily for 9-18 days Experimental Results: Significant tumor growth inhibition (TGI) in HCT116 and A549 models . |
| 参考文献 |
[1]. Murray, Brion W., et al. Small-molecule p21-activated kinase inhibitor PF3758309 is a potent inhibitor of oncogenic signaling and tumor growth. Proceedings of the National Academy of Sciences of the United States of America (2010), 107(20), 9446-9451, S94
[2]. Zhao ZS, et al. Do PAKs make good drug targets? F1000 Biol Rep. 2010 Sep 23;2:70. [3]. Ryu BJ, et al. PF-3758309, p21-activated kinase 4 inhibitor, suppresses migration and invasion of A549 human lung cancer cells via regulation of CREB, NF-κB, and β-catenin signalings. Mol Cell Biochem. 2014 Apr;389(1-2):69-77. [4]. Pitts TM, et al. Association of the epithelial-to-mesenchymal transition phenotype with responsiveness to the p21-activated kinase inhibitor, PF-3758309, in colon cancer models. Front Pharmacol. 2013 Mar 28;4:35. |
| 分子式 |
C25H30N8OS
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|---|---|---|
| 分子量 |
490.62
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| CAS号 |
898044-15-0
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| 相关CAS号 |
PF-3758309 hydrochloride;1279034-84-2;PF-3758309 dihydrochloride
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| SMILES |
S1C([H])=C([H])C2=C1C(=NC(C([H])([H])[H])=N2)N([H])C1C2C([H])([H])N(C(N([H])[C@@]([H])(C3C([H])=C([H])C([H])=C([H])C=3[H])C([H])([H])N(C([H])([H])[H])C([H])([H])[H])=O)C(C([H])([H])[H])(C([H])([H])[H])C=2N([H])N=1
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| InChi Key |
AYCPARAPKDAOEN-LJQANCHMSA-N
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| InChi Code |
InChI=1S/C25H30N8OS/c1-15-26-18-11-12-35-20(18)23(27-15)29-22-17-13-33(25(2,3)21(17)30-31-22)24(34)28-19(14-32(4)5)16-9-7-6-8-10-16/h6-12,19H,13-14H2,1-5H3,(H,28,34)(H2,26,27,29,30,31)/t19-/m1/s1
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| 化学名 |
(S)-N-(2-(dimethylamino)-1-phenylethyl)-6,6-dimethyl-3-((2-methylthieno[3,2-d]pyrimidin-4-yl)amino)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide.
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| 别名 |
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| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 运输条件 |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| 溶解度 (体外) |
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| 溶解度 (体内) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.10 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.10 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.10 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. 1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL； 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果，工作液请现配现用！ 6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
| 制备储备液 | 1 mg | 5 mg | 10 mg | |
| 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 |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
计算结果:
工作液浓度： mg/mL；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
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Structural characterization of PF-3758309 binding to the PAK4 catalytic domain.Proc Natl Acad Sci U S A.2010 May 18;107(20):9446-51. |
Tumor growth inhibition of human xenograft tumor models.
PF-3758309 is antiproliferative and induces apoptosis in a HCT116 tumor model.Proc Natl Acad Sci U S A.2010 May 18;107(20):9446-51. |
IPA-3
FRAX597
LCH-7749944
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