| 名稱 | Flavopiridol hydrochloride |
| 描述 | Flavopiridol hydrochloride (MDL 107826A) is a synthetic N-methylpiperidinyl chlorophenyl flavone compound. As an inhibitor of cyclin-dependent kinase, alvocidib induces cell cycle arrest by preventing phosphorylation of cyclin-dependent kinases (CDKs) and by down-regulating cyclin D1 and D3 expression, resulting in G1 cell cycle arrest and apoptosis. This agent is also a competitive inhibitor of adenosine triphosphate activity. |
| 細(xì)胞實(shí)驗(yàn) | Cells grown at a density of 1 × 106 cells/mL are exposed to Flavopiridol for different concentrations and time periods. DNA is extracted. Briefly, cells are washed once with cold phosphate-buffered saline (PBS) and lysed with 3 mL lysis buffer (5 mM Tris-HCL [pH 7.5]; 20 mM EDTA; 0.5% Triton X-100) for 15 minutes at 4 °C. The chromatin of the cell lysates is isolated by centrifugation (20 minutes at 26,000 g, 4 °C). The supernatants containing small DNA fragments are extracted sequentially with phenol, phenol:chloroform (1:1), and chloroform. Nucleic acids are precipitated in 0.5 M NaCl, 90% ethanol at -20 °C overnight. RNA is then digested by bovine RNAaseA (60 μg/mL). After sequential reextraction and reprecipitation, DNA is dissolved in 10 mM Tris-HCL (pH 7.5), 1 mM EDTA, 0.5% sodium dodecyl sulfate (SDS) before electrophoresis on 1.6% agarose gel. (Only for Reference) |
| 激酶實(shí)驗(yàn) | Recombinant CDKs Kinase Reactions: CDKs activities are determined in microtiter plates as follows. Forty μg Gst-Rb are mixed with different amounts of Flavopiridol and unlabeled ATP. Reactions are then started by the addition of an ammonium sulfate cut of the S100 fraction obtained from insect cells expressing recombinant human CDKs. The final reaction conditions are 10 mM MgCl2, 50 mM Tris-HCl (pH 7.5), and 1 mM DTT. The final concentration of ATP is adjusted accordingly. Radiolabeled ATP is used as a phosphoryl donor. The reaction is carried out for 2.5 minutes at 30 °C after addition of enzyme and then terminated with the addition of EDTA. The Gst-Rb is then captured with glutathione-Sepharose and the incorporated radioactivity is determined by liquid scintillation counting. |
| 體外活性 | 在SUDHL-4皮下注射淋巴瘤模型的老鼠中靜脈注射7.5 mg/kg Flavopiridol,模型鼠的腫瘤大部分（8分之2）或者完全（8分之4）消退,其中兩只動(dòng)物保持無(wú)病狀持續(xù)60天以上,整體生長(zhǎng)延遲73.2％.每天以最大耐受劑量10 mg/kg 口服給藥Flavopiridol,在第1-4天及7-11天,影響PRXF1337的腫瘤消退,在PRXF1369中腫瘤停滯持續(xù)4周.用7.5 mg/kg Flavopiridol靜脈內(nèi)、或腹膜內(nèi)連續(xù)注射Flavopiridol5天后,12個(gè)晚期皮下（sc）人HL-60異種移植鼠中的11個(gè)腫瘤完全消退,治療一療程后移植鼠數(shù)月無(wú)病. |
| 體內(nèi)活性 | Flavopiridol以時(shí)間和濃度依賴性方式誘導(dǎo)人類乳腺癌細(xì)胞G1期阻滯并抑制CDK2和CDK4。 Flavopiridol約12小時(shí)的短時(shí)處理,會(huì)誘導(dǎo)造血細(xì)胞系（包括SUDHL4,SUDHL6（B細(xì)胞系）,Jurkat和MOLT4（T細(xì)胞系）和HL60（骨髓））的細(xì)胞凋亡。一項(xiàng)研究Flavopiridol處理可誘導(dǎo)人成膠質(zhì)細(xì)胞瘤T98 g細(xì)胞系產(chǎn)生大量的AKT-Ser473磷酸化。在克隆形成實(shí)驗(yàn)中,Flavopiridol在23人腫瘤模型中作為高效的細(xì)胞毒性化合物,平均IC70是8 ng/mL。 |
| 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 | H2O : 43.8 mg/mL (99.93 mM), Sonication is recommended.
DMSO : 43.8 mg/mL (99.93 mM), Sonication is recommended.
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| 關(guān)鍵字 | NSC-649890 | NSC649890 | L86-8275 | Inhibitor | inhibit | Human immunodeficiency virus | HMR-1275 | HMR1275 | HMR 1275 | HL-275 | HL275 | HIVProtease | HIV Protease | HIV | Flavopiridol hydrochloride | Flavopiridol Hydrochloride | Flavopiridol | Cyclin dependent kinase | CDK7 | CDK6 | CDK4 | CDK2 | CDK1 | CDK | Autophagy | Alvocidib |
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