| 名稱 | Ribociclib |
| 描述 | Ribociclib (LEE011) is a cell cycle protein-dependent kinase CDK4/6 inhibitor (IC50 = 10/39 nM) with specific and oral activity. Ribociclib has antitumor activity that blocks the cell cycle and inhibits tumor cell proliferation. |
| 細(xì)胞實(shí)驗(yàn) | A panel of neuroblastoma cell lines, selected based upon prior demonstration of substrate adherent growth, is plated in triplicate on the Xcelligence Real-Time Cell Electronic Sensing system and treated 24 hours later with a four-log dose range of inhibitor or with a dimethyl sulfoxide (DMSO) control. Cell indexes are monitored continuously for ~100 hours, and IC50 values are determined as follows: growth curves are generated by plotting the cell index as a function of time and are normalized to the cell index at the time of treatment for a baseline cell index of 1. The area under the normalized growth curve from the time of treatment to 96 hours posttreatment is then calculated using a baseline area of 1 (the cell index at the time of treatment). Areas are normalized to the DMSO control, and the resulting data are analyzed using a nonlinear log inhibitor versus normalized response function. All experiments are repeated at least once. (Only for Reference) |
| 激酶實(shí)驗(yàn) | Enzyme assays are performed using a homogeneous time-resolved fluorescence assay with recombinant epitope tagged kinase domains (JAK1, 837-1142; JAK2, 828-1132; JAK3, 718-1124; Tyk2, 873-1187) or full-length enzyme (cMET and Chk2) and peptide substrate. Each enzyme reaction is performed with or without test compound (11-point dilution), JAK, cMET, or Chk2 enzyme, 500 nM (100 nM for Chk2) peptide, ATP (at the Km specific for each kinase or 1 mM), and 2.0% DMSO in assay buffer. The calculated IC50 value is the compound concentration required for inhibition of 50% of the fluorescent signal. Additional kinase assays are performed at Cerep using standard conditions at 200 nM. Enzymes tested included: Abl, Akt1, AurA, AurB, CDC2, CDK2, CDK4, CHK2, c-kit, EGFR, EphB4, ERK1, ERK2, FLT-1, HER2, IGF1R, IKKα, IKKβ, JNK1, Lck, MEK1, p38α, p70S6K, PKA, PKCα, Src, and ZAP70[1]. |
| 體外活性 | 方法：人乳腺癌細(xì)胞 MDA-MB-231 用 Ribociclib (0-20 μM) 處理 24-144 h，使用 CCK8 assay 檢測(cè)細(xì)胞活力。
結(jié)果：Ribociclib 抑制 MDA-MB-231 中的細(xì)胞增殖。[1]
方法：神經(jīng)母細(xì)胞瘤細(xì)胞系 BE2C、IMR5、EBC1 和 SKNAS 用 Ribociclib (0.01-10 μM) 處理 96 h，使用 Western Blot 檢測(cè)靶點(diǎn)蛋白表達(dá)水平。
結(jié)果：在 BE2C 和 IMR5 細(xì)胞系中，從 250 nM 開始觀察到 pRBS780 的耗竭。在 EBC1 和 SKNAS 抗性細(xì)胞系中也觀察到 pRBS780 的降低，但僅在較高的抑制劑濃度下。[2] |
| 體內(nèi)活性 | 方法：為測(cè)試體內(nèi)抗腫瘤活性，將 Ribociclib (200 mg/kg in 0.5 % methylcellulose) 口服給藥給攜帶神經(jīng)母細(xì)胞瘤 BE2C、NB-1643 或 EBC1 的 CB17 小鼠，每天一次，持續(xù)二十一天。
結(jié)果：在攜帶 BE2C 或 1643 異種移植物的小鼠中，腫瘤生長(zhǎng)在整個(gè) 21 天的治療過程中顯著延遲。在 EBC1 異種移植物模型中，腫瘤生長(zhǎng)抑制不那么有力。[2] |
| 存儲(chǔ)條件 | store under nitrogen | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 50 mg/mL (115.06 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 5 mg/mL (11.51 mM), Suspension. Please add co-solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately.
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | Cyclin dependent kinase | inhibit | Inhibitor | LEE 011 | Ribociclib | CDK | LEE-011 |
| 相關(guān)產(chǎn)品 | Sodium Oxamate | Axitinib | CASIN | Sorafenib tosylate | Lenvatinib mesylate | Regorafenib | Pazopanib | Nintedanib | Sorafenib | Regorafenib monohydrate | Dinaciclib | Abemaciclib |
| 相關(guān)庫 | 經(jīng)典已知活性庫 | 抗癌活性化合物庫 | 激酶抑制劑庫 | EMA 上市藥物庫 | 酪氨酸激酶分子庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |