|
受注：045-509-1970 |
技術サポート：tech@selleck.co.jp 平日9:00〜18:00 1営業日以内にご連絡を差し上げます |
化学情報
|
Synonyms | NSC 649890, HMR-1275, L86-8275 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C21H20ClNO5 |
|||
| 分子量 | 401.84 | CAS No. | 146426-40-6 | |
| Solubility (25°C)* | 体外 | DMSO | 30 mg/mL (74.65 mM) | |
| Water | Insoluble | |||
| Ethanol | Insoluble | |||
|
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
||||
溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | Flavopiridol (Alvocidib)は、ATPと競合して、CDK1、CDK2、CDK4、CDK6、CDK9を含むCDKを20〜100 nMのIC50値で阻害します。CDK7と比較して、CDK1、2、4、6、9に対してより選択的です。Flavopiridolは、当初、EGFRとPKAを阻害することがわかっています。FlavopiridolはautophagyとERストレスを誘発します。FlavopiridolはHIV-1複製をブロックします。フェーズ1/2。 |
|---|---|
| in vitro | Flavopiridol (Alvocidib) displays less activity against unrelated kinases such as MAP, PAK, PKC, and EGFR with IC50 of >14 μM. It significantly inhibits the colony growth of HCT116, A2780, PC3, and Mia PaCa-2 cells with IC50 of 13 nM, 15 nM, 10 nM and 36 nM, respecitively. This compound also potently inhibits the activity of Glycogen synthase kinase-3 (GSK-3) with an IC50 of 280 nm. Compared with other CDKs, it inhibits the activity of CDK7 less potently with IC50 of 875 nM. At 0.5 μM, it inhibits both pSer807/811 Rb and pThr199 NPM, whereas mild changes are observed at pThr821 Rb. It also decreases the overall RNA polymerase II level, as well as the phosphorylation of RNA polymerase II on the CTD repeats at Ser2 Ser5. As a broad spectrum CDK inhibitor, it can inhibit cell cycle progression in either G1 or G2. At 0.3 μM, it induces G1 arrest in either MCF-7 or MDA-MB-468 cells by inhibition of the CDK4 or CDK2 kinase activity. It exhibits potent cytotoxicity against a wide variety of tumor cell lines with IC50 values ranging form 16 nM for LNCAP to 130 nM for K562. |
| in vivo | Administration of S1230 at 7.5 mg/kg for 7 days displays slight antitumor activity against P388 murine leukemia, resulting in %T/C value of 110, and active against the human A2780 ovarian carcinoma implanted sc in nude mice, producing 1.5 log cell kill (LCK). S1230 treatment at 1-2.5 mg/kg for 10 days significantly suppresses collagen-induced arthritis in mice in a dose-dependent manner, by inhibiting synovial hyperplasia and joint destruction, whereas serum concentrations of anti-collagen type II (CII) Abs and proliferative responses to CII are maintained. In the p21-intact Hct116 xenografts in nude mice, administration of CPT-11 (100 mg/kg) followed by S1230 (3 mg/kg) 7 and 16 hours later significantly inhibits tumor regression by 86% and 82%, respectively, displaying >2 fold inhibition compared with CPT-11 alone by 40 %. The combination produces ~30% complete response rate (CR) in contrast to CPT-11 alone where no CR is found. |
| 特徴 | First CDK inhibitor to be used in human clinical trials. |
プロトコル(参考用のみ)
| キナーゼアッセイ | CDK kinase assay | |
|---|---|---|
| For CDK1/cyclin B1 kinase assay, kinase reactions consist of 100 ng of baculovirus expressed GST-CDK1/cyclin B1 (human) complex, 1 μg histone HI, 0.2 μCi [γ-33P]ATP, 25 μM ATP in 50 μL kinase buffer (50 mM Tris, pH 8.0, 10 mM MgCl2, 1 mM EGTA, 0.5 mM DTT). For CDK2/cyclin E kinase assay, kinase reactions consist of 5 ng of baculovirus expressed GST-CDK2/cyclin E (human) complex, 0.5 μg GST-RB fusion protein (amino acids 776-928 of retinoblastoma protein), 0.2 μCi [γ-33P]ATP, 25 μM ATP in 50 μL kinase buffer (50 mM Hepes, pH 8.0, 10 mM MgCl2, 1 mM EGTA, 2 mM DTT). For CDK4/cyclin D1 kinase assay, kinase reactions consist of 150 ng of baculovirus expressed GST-CDK4/cyclin D1 (human), 280 ng of Stag-cyclin D1, 0.5 μg GST-RB fusion protein (amino acids 776-928 of retinoblastoma protein), 0.2 μCi [γ-33P]ATP, 25 μM ATP in 50 μL kinase buffer (50 mM Hepes, pH 8.0, 10 mM MgCl2, 1 mM EGTA, 2 mM DTT). Reactions are incubated for 45 minutes for CDK1 and CDK2, or 1 hour for CDK4 at 30 °C and stopped by the addition of cold trichloroacetic acid (TCA) to a final concentration 15%. TCA precipitates are collected onto GF/C unifilter plates using a Filtermate universal harvester and the filters are quantitated using a TopCount 96-well liquid scintillation counter. Flavopiridol (Alvocidib) is dissolved at 10 mM in dimethylformamide (DMF) and evaluated at six concentrations, each in triplicate. The final concentration of DMF in the assay = 2%. IC50 values are derived by nonlinear regression analysis and have a coefficient of variance = 16%. To assay its activity on CDK6, a filter-binding assay is established. The following are combined in the reaction mixture: 2 μL of CDK6 (0.7 mg/μL), 5 μL of histone H1 (6 mg/mL), 14 μL of kinase buffer (60 mM β-glycerophosphate, 30 mM p-nitrophenyl phosphate, 25 mM MOPS (pH 7.0), 5 mM EGTA, 15 mM MgCl2, 1 mM DTT, 0.1 mM Na-vanadate), 3 μL of increasing concentrations of this compound diluted in 50% DMSO, and 6 μL of 33P-ATP (1 mCi/mL) in nonradioactive ATP at 90 μM concentration (final concentration: 15 μM). The assay is initiated by the addition of 33P-ATP. The reaction is incubated for 20 minutes at 30°C. A 25 μL aliquot of the supernatant is then spotted onto Whatman P81 phosphocellulose paper. Filters are washed 5 times with 1% phosphoric acid solution. Wet filters are counted in the presence of 1 mL of scintillation fluid. Cdk9 activity is measured using 50 nM of recombinant Cdk9/cyclin T in 50 mM HEPES pH 7.5, 10 mM MgCl2, 1 mM DTT, 3 μM Na3VO4, 150 μM RNA polymerase CDT peptide and 80 μM ATP. Cdk7 assay is performed in the same buffer using 37 nM of purified kinase in the presence of 200 μM ATP and 10 μM myelin binding protein as a substrate. The potency of it toward CDK9 and CDK7 is determined using either a strong anion exchanger (Dowex 1-X8 resin, formate form)-based assay or a scintillation proximity assay. IC50 values are calculated from the dose-response curves. | ||
| 細胞アッセイ | 細胞株 | MCF-7, LNCAP, PC3, HCT116, CACO-2, A549, HL60, K562 cells and et al. |
| 濃度 | Dissolved in DMSO, final concentrations ~10 μM | |
| 反応時間 | 72 hours | |
| 実験の流れ | Cells are exposed to various concentrations of Flavopiridol (Alvocidib) for 72 hours, at which time the tetrazolium dye, MTS in combination with phenazine methosulfate, is added. After 3 hours, the absorbency is measured at 492 nm, which is proportional to the number of viable cells. The results are expressed as IC50 values. For cell cycle analysis, cells are fixed in paraformaldehyde and ethanol, washed, resuspended in a staining solution of TdT enzyme and FITC-dUTP, washed, stained with PI following RNase treatment, and then analyzed by flow cytometry. |
|
| 動物実験 | 動物モデル | Female Balb/c×DBA/2J F1 mice inoculated ip with P388 ascites leukemic cells, and Balb/c nu/nu nude mice subcutaneous implanted with A2780, Br-cycE, or A431 cells |
| 投薬量 | ~7.5 mg/kg/day | |
| 投与方法 | Injection i.p. | |
参考
|
カスタマーフィードバック
-
Data from [PNAS, 2011, 108, 8417]
-
Data from [Data independently produced by , , Science, 2018, 11(530), doi: 10.1126/scisignal.aai8669]
-
Data from [Data independently produced by , , Cancer Res, 2016, 76(5):1158-69]
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| SLFN11-mediated ribosome biogenesis impairment induces TP53-independent apoptosis [ Mol Cell, 2025, S1097-2765(25)00042-5] | PubMed: 39909041 |
| Combined therapy with DR5-targeting antibody-drug conjugate and CDK inhibitors as a strategy for advanced colorectal cancer [ Cell Rep Med, 2025, S2666-3791(25)00231-9] | PubMed: 40449480 |
| Maternal CENP-C restores centromere symmetry in mammalian zygotes to ensure proper chromosome segregation [ Dev Cell, 2025, S1534-5807(25)00537-4] | PubMed: 40997799 |
| Identification of modulators of the ALT pathway through a native FISH-based optical screen [ Cell Rep, 2025, 44(1):115114] | PubMed: 39729394 |
| Identifying Age-Modulating Compounds Using a Novel Computational Framework for Evaluating Transcriptional Age [ Aging Cell, 2025, e70075] | PubMed: 40307992 |
| Protection of infant mice against pertussis, tuberculosis and influenza by co-administration of nasal pertussis vaccine candidate BPZE1 and BCG [ iScience, 2025, 28(7):112839] | PubMed: 40612502 |
| Replication-competent adenovirus reporters utilizing endogenous viral expression architecture [ J Virol, 2025, 99(10):e0114625] | PubMed: 40928252 |
| BET degraders reveal BRD4 disruption of 7SK and P-TEFb is critical for effective reactivation of latent HIV in CD4+ T-cells [ J Virol, 2025, 99(4):e0177724] | PubMed: 40067013 |
| Repurposing flavopiridol as an inhaled therapeutic for pulmonary fibrosis [ Eur J Pharmacol, 2025, 1005:178058] | PubMed: 40816528 |
| Bacterial ubiquitin ligase engineered for small molecule and protein target identification [ bioRxiv, 2025, 2025.03.20.644192] | PubMed: 40166235 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。