| 名称 | PF-3758309 |
| 描述 | PF-3758309 (PF-03758309) (IC50=1.3 nM), a pyrrolopyrazole inhibitor of PAK4, has effective ATP-competition. |
| 细胞实验 | HEK293T, HCT116, and SKOV3 cells are plated on 384-well plates for 24 hours culture. PF-3758309( ~1 μM) is added to the cell culture incubating 72 hours. After drug treatment,cell proliferation and other indicators of metabolism are measured. |
| 激酶实验 | In phospho-GEF-H1 cellular assay, TR-293-KDG cells are incubated for 3 hours with PF-3758309. TR-293-KDG cells were captured on an anti-HA antibody-coated plate, which is detected with an anti-phospho-S810-GEF-H1 antibody, and quantified with a horseradish peroxidase-goat anti-rabbit antibody conjugate. TR-293-KDG cells are constructed from HEK293 cells, which is transfected with tetracycline-inducible PAK4-kinase domain (amino acids 291-591) and expressed HA-tagged GEFH1ΔDH (amino acids 210-921). |
| 动物实验 | Nude mice with Xenograft tumors were orally fed with PF-3758309（7.5-30 mg/kg BID）dissolved in 0.5% methylcellulose. |
| 体外活性 | PF-3758309 (Kd = 2.7 nM), an effective inhibitor of PAK4 （Ki=18.7 nM）, has ATP competition. PF-3758309 (IC50 = 1.3 nM) inhibits phosphorylation of the PAK4 substrate GEF-H1 in cells. In the tumor cell, PF-3758309(IC50 = 4.7 nM) grows in a linesanchorage-independent manner. In HCT116 cells, PF-3758309 inhibits endogenous pGEF-H1 accumulation. In A549 cells, PF-3758309 effectively inhibits cellular proliferation in IC50 of 20 nM and anchorage-independent growth in IC50 of 27 nM. |
| 体内活性 | In the HCT116 tumor model, PF-3758309 act as an antiproliferative inducing apoptosis. In the sensitive model, PF-3758309 (EC50=0.4 nM) blocks the growth of multiple human tumor xenografts. |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 3.3 mg/mL (6.73 mM), Sonication is recommended.
DMSO : 150 mg/mL (305.74 mM), Sonication is recommended.
Ethanol : 91 mg/mL (185.48 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| 关键字 | tumor | survival | signaling | proliferation | PF-3758309 | PF3758309 | PF309 | PF03758309 | PF 309 | PF 03758309 | PAK6 | PAK5 | PAK4 | PAK3 | PAK1 | PAK | p21 activated kinases | oncogenic | Inhibitor | inhibit | growth | ATP-competitive | Apoptosis |
| 相关产品 | Urea | Dimethyl phthalate | Aceglutamide | Alginic acid | Cysteamine hydrochloride | Metronidazole | Dextran sulfate sodium salt (MW 5000) | Citric Acid Triammonium | Gum arabic | Stavudine | Tamoxifen | Sodium 4-phenylbutyrate |
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