| 名称 | PF04929113 |
| 描述 | PF04929113 (SNX-5422) is a synthetic, novel, small molecule Hsp90 Inhibitor. As an oral formulation that demonstrates strong efficacy and tolerability, PF04929113 is positioned as a breakthrough therapy with broad applicability across a wide range of cancers. |
| 细胞实验 | Cell lines: MCF-7,SW620,K562,SK-MEL-5 and A375 cancer cell lines. Concentrations: 0-300 nM. Method: Proliferation rates are measured by seeding cells into 96-well plates,followed by compound addition 24 h later.After addition of PF-04929113,cells are allowed to grow for either an additional 72 or 144 h depending on the rate of growth.At harvest,media is removed and DNA content for individual wells is determined using CyQuant DNA dye.Levels of Hsp90 client proteins and phosphor-regulated proteins in A375 are measured by high content analysis (HCA) using an ArrayScan 4.5 instrument after 24 hours of treatment with PF-04929113,followed by methanol fixation.After fixation in 4% PBS-buffered formalin and permeablization with 0.1% TX-100,cells are probed with anti-Her2,antiphospho-S6 (pS6),antipERK,and anti-Hsp70 primary antibodies,followed by TRITC or FITC conjugated secondary antibodies.Nuclei are also stained with Hoechst DNA binding dye.For each well,250-500 individual nuclei are identified along with the average staining intensity for the client and phospho-proteins for each cell.Average client staining intensities are then calculated for each well. |
| 激酶实验 | The Hsp90 loaded media is challenged with PF-04929113 at a given concentration, ranging from 0.8 to 500 μM, and the amount of Hsp90 liberated at each concentration is determined by Bradford protein assay. The resulting IC50 values are corrected for the ATP ligand concentration and presented as apparent Kd values. |
| 动物实验 | Animal Models: 5 ×106 MM.1S cells are inoculated subcutaneously in the Fox Chase SCID mice (6-7 weeks old). Formulation: PF-04929113 is dissolved in 1% carboxy methylcellulose/0.5% Tween 80 at 10 mg/mL and stored at 4 °C. Dosages: 20 or 40 mg/kg. Administration: orally 3 times per week,3 weeks in total. |
| 体外活性 | 免疫组织化学分析表明,在用PF-04929113处理后,SP70表达增加,并降低Ki67,Akt和AR表达.PF-04929113在体内抑制人类MM细胞生长,并且免疫组织化学分析显示PF-04929113显著抑制处理的小鼠中的p-ERK和p-Akt.同时,PF-04929113处理显著降低CD31+细胞和MVD百分比,与体内血管生成的抑制作用一致.PF-04929113对肿瘤发展的抑制可能由增殖减少（Ki67和Akt表达降低）或凋亡率增加（增加的ApopTag染色）共同引起. |
| 体内活性 | PF-04929113对Her-2稳定性表现出有效的作用并导致预期的Hsp70上调。PF-04929113显示针对广泛癌症细胞类型的有效抗增殖活性,例如,MCF-7（IC50 = 16 nM）,SW620（IC50 = 19 nM）,K562（IC50 = 23 nM）,SK-MEL-5（IC50 = 25 nM）和A375（IC50 = 51 nM）。 |
| 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 : 2.5 mg/mL (4.79 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : 3 mg/mL (5.75 mM), Sonication is recommended.
DMSO : 96 mg/mL (184.07 mM), Sonication is recommended.
|
| 关键字 | SNX5422 | SNX 5422 | PF04929113 | HSP90 | HER2 |
| 相关产品 | Neratinib | Teprenone | 17-AEP-GA | Afatinib Dimaleate | Tannic acid | Rifabutin | Tucatinib | Palmitic acid | VU 0240551 | Paeoniflorin | Tamoxifen | Ethoxyquin |
| 相关库 | 肿瘤免疫治疗小分子化合物库 | 抗癌活性化合物库 | 经典已知活性库 | 已知活性化合物库 | 代谢化合物库 | HIF-1化合物库 | 膜蛋白靶向化合物库 | 酪氨酸激酶分子库 | 药物功能重定位化合物库 | 抗癌临床化合物库 | 内质网应激化合物库 | 抗癌药物库 |