| Name | PF-3758309 |
| Description | PF-3758309 (PF-03758309) (IC50=1.3 nM), a pyrrolopyrazole inhibitor of PAK4, has effective ATP-competition. |
| Cell Research | 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. |
| Kinase Assay | 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). |
| Animal Research | Nude mice with Xenograft tumors were orally fed with PF-3758309（7.5-30 mg/kg BID）dissolved in 0.5% methylcellulose. |
| In vitro | 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. |
| In vivo | 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. |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | DMSO : 91 mg/mL (185.5 mM)
Ethanol : 91 mg/mL (185.5 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| Keywords | PF-3758309 | proliferation | tumor | oncogenic | survival | PF03758309 | inhibit | p21 activated kinases | signaling | Apoptosis | ATP-competitive | PF 309 | PF 03758309 | Inhibitor | PF3758309 | growth | PF309 | PAK |
| Inhibitors Related | Stavudine | 5-Fluorouracil | Acetylcysteine | Kaempferol | Myricetin | Sodium 4-phenylbutyrate | L-Ascorbic acid | Dextran sulfate sodium salt (MW 4500-5500) | Metronidazole | Sorafenib | Tributyrin | Lidocaine hydrochloride |
| Related Compound Libraries | 经典已知活性库 | 激酶抑制剂库 | 抗癌临床化合物库 | 药物功能重定位化合物库 | 抑制剂库 | NO PAINS 化合物库 | 抗衰老化合物库 | 已知活性化合物库 | 抗癌活性化合物库 | 抗癌药物库 |
United States
