| 名稱 | ENMD-2076 |
| 描述 | ENMD-2076, a multi-targeted kinase inhibitor, has specific activity against Aurora A, Flt3, KDR/VEGFR2, Flt4/VEGFR3, FGFR1, FGFR2, Src, PDGFRα. |
| 細(xì)胞實(shí)驗(yàn) | The antiproliferative effect of ENMD-2076 on adherent tumor cell lines is measured by plating 500 cells per well in a 96-well plate and incubating with ENMD-2076 for 96 hours. Cellular proliferation is measured using the sulforhodamine B assay. The leukemia-derived, nonadherent cell lines are assayed by plating 5 × 103 cells per well in a 96-well plate. The cells are incubated with ENMD-2076 for 48 hours and then survival is assayed using the Alamar Blue reagent. To measure the effect of ENMD-2076 on VEGF- and fibroblast growth factor (FGF)-induced proliferation of human umbilical vein endothelial cell (HUVEC), cells are serum starved for 6 hours, then treated with ENMD-2076 free base, and stimulated with 5 ng/mL bFGF or 25 ng/mL VEGF (R and D Systems) for 72 hours. Cell proliferation is measured using WST-(Only for Reference) |
| 激酶實(shí)驗(yàn) | Kinase assays: Recombinant Aurora A and B kinase enzymes and appropriate PanVera Z'-Lyte kinase assay kits are purchased. Assays are carried out in kinase assay buffer (50 mM of HEPES, pH 7.5, 10 mM of MgCl2, 5 mM of EGTA, 0.05% Brij-35) supplemented with 2 mM of DTT. Activities are determined at an ATP concentration equivalent to the apparent Km for each enzyme, and an enzyme concentration that results in approximately 30% phosphorylation of the peptide substrate after 1 hour. Dose–response curves of relative enzyme activity versus ENMD-2076 concentration are plotted with Grafit and used to calculate IC50 values. Potency of ENMD-2076 free base against a select panel of 100 kinase enzymes is determined using the SelectScreen kinase profiling service. ATP concentrations are at the apparent Km for each enzyme or 100 μM if the apparent Km could not be reached. Percent inhibition is determined at an ENMD-2076 free base concentration of 1 μM; for kinases where significant inhibition is noted, IC50 values are determined by generating full 10-point dose–response curves. |
| 體外活性 | 在MDA-MB-231異種移植模型中, ENMD-2076可以抑制形成新血管,同時(shí)使形成的血管發(fā)生退化.在HT29異種移植模型中,ENMD-2076對Flt3以及VEGFR2 / KDR和FGFR1 / 2的激活持續(xù)發(fā)揮抑制作用.在H929人漿細(xì)胞瘤異種移植物中,口服ENMD-2076（50-200 mg / kg /day）,其中磷酸 - 組蛋白3（pH3）,Ki-67顯著降低,裂解的胱天蛋白酶-3顯著增加. |
| 體內(nèi)活性 | ENMD-2076作用于PI3K/AKT通路,下調(diào)凋亡抑制蛋白。ENMD-2076能夠抑制aurora A和B激酶,且誘導(dǎo)細(xì)胞周期停在G2/M 期。在多種作用于血管生成的激酶中（IC50=1.86-120 nM）,ENMD-2076能夠發(fā)揮作用,比如VEGFR2/KDR 和VEGFR3, FGFR1和FGFR2, 及PDGFRα。在多種人類實(shí)體瘤和血癌細(xì)胞系中（IC50=0.025 -0.7 μM）,ENMD-2076使細(xì)胞停滯在G2/M 期,誘導(dǎo)細(xì)胞凋亡 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 97 mg/mL (258.3 mM)
H2O : 1 mg/mL (2.66 mM)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | Cluster of differentiation antigen 135 | FLT3 | Aurora Kinase | Inhibitor | Apoptosis | Fibroblast growth factor receptor | CD135 | VEGFR | Platelet-derived growth factor receptor | ENMD 2076 | ENMD2076 | FGFR | ENMD-2076 | Vascular endothelial growth factor receptor | Fms like tyrosine kinase 3 | PDGFR | Src | inhibit |
| 相關(guān)產(chǎn)品 | L-Glutamic acid | Metronidazole | Ferulic Acid | 5-Fluorouracil | Dextran sulfate sodium salt (MW 4500-5500) | Stavudine | Tributyrin | Myricetin | L-Ascorbic acid | Acetylcysteine | Salicylic acid | Sodium 4-phenylbutyrate |
| 相關(guān)庫 | 抑制劑庫 | 抗癌活性化合物庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 抗衰老化合物庫 | 膜蛋白靶向化合物庫 | 酪氨酸激酶分子庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |