| 名稱 | CYC-116 |
| 描述 | CYC116 is a potent inhibitor of Aurora A/B with Ki of 8.0 nM/9.2 nM, is less potent to VEGFR2 (Ki of 44 nM), with 50-fold greater potency than CDKs, not active against PKA, Akt/PKB, PKC, no effect on GSK-3α/β, CK2, Plk1 and SAPK2A. Phase 1. |
| 細(xì)胞實(shí)驗(yàn) | Standard MTT assays are performed. In short, cells are seeded into 96-well plates according to doubling time and incubated overnight at 37°C. Test compounds are made up in DMSO, a 3-fold dilution series is prepared in 100 μL of cell medium, added to cells (in triplicates) and incubated for 72 or 96 hours at 37°C. MTT is made up as a stock of 5 mg/mL in cell medium, and the solution is filter-sterilized. Medium is removed from the cells followed by a wash with PBS. MTT solution is then added at 20 μL/well and incubated in the dark at 37°C for 4 hours. MTT solution is removed and cells are again washed with 200 μL of PBS. MTT dye is solubilized with 200 μL/well of DMSO by agitation. Absorbance is read at 540 nm and data analyzed using curve-fitting software to determine IC50 values. (Only for Reference) |
| 激酶實(shí)驗(yàn) | Kinase Assays: Aurora A kinase assays are performed using a 25 μL reaction volume (25 mM β-glycerophosphate, 20 mM Tris/HCl, pH 7.5, 5 mM EGTA, 1 mM DTT, 1 mM Na3VO4, 10 μg of kemptide (peptide substrate)). Recombinant Aurora A kinase is diluted in 20 mM Tris/HCl, pH 8, containing 0.5 mg/mL BSA, 2.5% glycerol, and 0.006% Brij-35. Reactions are started by the addition of 5 μL Mg/ATP mix (15 mM MgCl2, 100 μM ATP, with 18.5 kBq γ-32P-ATP per well) and incubated at 30°C for 30 minutes before termination with 25 μL of 75 mM H3PO4. Aurora B kinase assays are performed like Aurora A except that prior to use, Aurora B is activated in a separate reaction at 30°C for 60 minutes with inner centromere protein. |
| 體外活性 | The most Aurora-selective CYC116 shows inhibitory effect on Aurora A and B kinases 50-fold more potently than any of the CDKs assayed. [1] CYC116 is initially screened against a panel of human leukemia and solid tumor cell lines using an MTT antiproliferative assay. The results show that CYC116 has broad-spectrum antitumor activity and shows specific cytotoxicity against the acute myelogenous leukemia cell line MV4-11 with IC50 of 34 nM. [1] In addition, anti-proliferative activity of CYC116 is found to be associated with Aurora A and B modulation such as, inhibition of Aurora autophosphorylation, reduction of histone H3 phosphorylation, polyploidy, followed by cell death, resulting from a failure in cytokinesis. [1] |
| 體內(nèi)活性 | Mice bearing subcutaneous NCI-H460 xenografts are given CYC116 orally for 5 days, at dose levels of 75 and 100 mg/kg q.d. It leads to tumor growth delays of 2.3 and 5.8 days, which translated into specific growth delays of 0.32 and 0.81, respectively. [1] |
| 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 : < 1 mg/mL
H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
|
| 關(guān)鍵字 | Inhibitor | inhibit | CYC-116 | CYC116 | CYC 116 | Aurora Kinase |
| 相關(guān)產(chǎn)品 | Sodium Oxamate | Gilteritinib | Ribociclib | Sodium salicylate | Axitinib | CASIN | Regorafenib | Pazopanib | Nintedanib | Sorafenib | Regorafenib monohydrate | Abemaciclib |
| 相關(guān)庫(kù) | 抑制劑庫(kù) | 抗癌活性化合物庫(kù) | 經(jīng)典已知活性庫(kù) | 激酶抑制劑庫(kù) | 抗衰老化合物庫(kù) | 膜蛋白靶向化合物庫(kù) | 免疫/炎癥分子化合物庫(kù) | 藥物功能重定位化合物庫(kù) | 酪氨酸激酶分子庫(kù) | 疼痛相關(guān)化合物庫(kù) | 抗癌臨床化合物庫(kù) | 抗癌藥物庫(kù) |