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化学情報
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C28H39N7O3 |
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| 分子量 | 521.66 | CAS No. | 755038-02-9 | |
| Solubility (25°C)* | 体外 | DMSO | 100 mg/mL (191.69 mM) | |
| Ethanol | 100 mg/mL (191.69 mM) | |||
| Water | Insoluble | |||
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* <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. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | BI-2536 is a potent Plk1 inhibitor with IC50 of 0.83 nM in a cell-free assay. BI-2536 inhibits Bromodomain 4 (BRD4) with Kd of 37 nM and potently suppresses c-Myc expression. BI-2536 induces apoptosis and attenuates autophagy. Phase 2. |
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| in vitro | BI 2536 blocks the activities of Plk2 and Plk3 to a slightly lesser extent with IC50 of 3.5 nM and 9.0 nM, respectively. In HeLa cells, BI 2536 treatment ranging from 10-100 nM leads to the blocking of the recruitment of γ-tubulin and phosphorylation of Apc6 at mitotic centrosomes, inhibition of cohesin release from chromosome arms, induction of monopolar spindles, as well as a range of other mitotic processes that are known to depend on Plk1. BI 2536 treatment leads to the HeLa cells arrested in G2/M, subsequently a sub-G1 DNA peak indicative of DNA breakdown and apoptosis, and accumulated cleaved PARP p85 fragments in a concentration-dependent manner. BI 2536 inhibits the growth of a panel of 32 human cancer cell lines with EC50 of 2-25 nM, while blocking the proliferation of exponentially growing hTERT-RPE1, human umbilical vein endothelial cells (HUVECs), and normal rat kidney (NRK) cells with EC50 of 12-31 nM. [1] Plk1 inhibition by BI 2536 reduces the growth and viability of anaplastic thyroid carcinoma (ATC) cells such as CAL62, OCUT-1, SW1736, 8505C, and ACT-1 with EC50 values of 1.4-5.6 nM. [2] |
| in vivo | BI 2536 given i.v. once or twice per week is highly efficacious in diverse xenograft models with acceptable tolerability by inhibiting cell proliferation through a mitotic arrest, and subsequently induction of tumor-cell death. Administration of BI 2536 at 50 mg/kg once or twice per week significantly inhibits growth of HCT 116 xenografts with T/C of 15% and 0.3%, respectively. BI 2536 treatment twice-weekly also leads to excellent tumor-growth in BxPC-3 and A549 models with T/C of 5% and 14%, respectively. [1] |
| 特徴 | The first potent and selective Plk1 inhibitor that induces all hallmarks of Plk1 inhibition. |
プロトコル(参考用のみ)
| キナーゼアッセイ | Plk1 in vitro kinase assay | |
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| Recombinant human Plk1 (residues 1-603) is expressed as N-terminal, GST-tagged fusion protein with a baculoviral expression system and purified by affinity chromatography with Glutathione-agarose. Enzyme activity assays for Plk1 are performed in the presence of serially diluted BI 2536 with 20 ng of recombinant kinase and 10 μg casein from bovine milk as the substrate. Kinase reactions are performed in a final volume of 60 μL for 45 minutes at 30 °C (15 mM MgCl2, 25 mM MOPS [pH 7.0], 1 mM DTT, 1% DMSO, 7.5 mM ATP, 0.3 μCi γ-33P-ATP). Reactions are terminated by the addition of 125 μL of ice-cold 5% TCA. After transfer of the precipitates to Multi-Screen mixed ester cellulose filter plates, plates are washed with 1% TCA and quantified radiometrically. Dose-response curve is used for calculating IC50 value. | ||
| 細胞アッセイ | 細胞株 | HeLa, A43, SKOV-3, HT-29, K562, A549, Saos-2, MCF7, HCT116, COLO 205, Hep G2, Raji and PC-3 cells, etc. |
| 濃度 | Dissolved in DMSO, final concentrations ~1 μM | |
| 反応時間 | 24 and 72 hours | |
| 実験の流れ | Cells are exposed to various concentrations of BI 2536 for 24, and 72 hours. Cell growth is assessed by the measurement of Alamar Blue dye conversion in a fluorescence spectrophotometer. For determining the DNA content of the cultures, cell suspensions are fixed in 80% ethanol, treated for 5 minutes with 0.25% Triton X-100 in PBS, and incubated with 0.1% RNase and 10 μg/mL propidium iodide (PI) in PBS for 20 minutes at RT. Cell-cycle profiles are determined by flow cytometric analysis. |
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| 動物実験 | 動物モデル | Female BomTac:NMRI-Foxn1nu mice injected subcutaneously with HCT 116, NCI-H460, or A549 cells |
| 投薬量 | ~50 mg/kg | |
| 投与方法 | Injection i.v. once or twice per week | |
参考
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カスタマーフィードバック
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Data from [J Biomol Screen, 2013, 18(1), 54-66]
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Data from [J Biomol Screen, 2013, 18(1), 54-66]
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Data from [J Biol Chem, 2012, 287(21), 17088-99]
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：
| Polθ is phosphorylated by PLK1 to repair double-strand breaks in mitosis [ Nature, 2023, 621(7978):415-422] | PubMed: 37674080 |
| Cellular Heterogeneity of Activated Primary Human Macrophages and Associated Drug-Gene Networks: From Biology to Precision Therapeutics [ Circulation, 2023, 148(19):1459-1478] | PubMed: 37850387 |
| Mild replication stress causes premature centriole disengagement via a sub-critical Plk1 activity under the control of ATR-Chk1 [ Nat Commun, 2023, 14(1):6088] | PubMed: 37773176 |
| Molecular landscape and functional characterization of centrosome amplification in ovarian cancer [ Nat Commun, 2023, 14(1):6505] | PubMed: 37845213 |
| Master mitotic kinases regulate viral genome delivery during papillomavirus cell entry [ Nat Commun, 2023, 14(1):355] | PubMed: 36683055 |
| Oocytes can repair DNA damage during meiosis via a microtubule-dependent recruitment of CIP2A-MDC1-TOPBP1 complex from spindle pole to chromosomes [ Nucleic Acids Res, 2023, 51(10):4899-4913] | PubMed: 36999590 |
| Dynamic physiological α-synuclein S129 phosphorylation is driven by neuronal activity [ NPJ Parkinsons Dis, 2023, 9(1):4] | PubMed: 36646701 |
| USP1 promotes the aerobic glycolysis and progression of T-cell acute lymphoblastic leukemia via PLK1/LDHA axis [ Blood Adv, 2023, 7(13):3099-3112] | PubMed: 36912760 |
| Polo‑like kinase 1 selective inhibitor BI2536 (dihydropteridinone) disrupts centrosome homeostasis via ATM‑ERK cascade in adrenocortical carcinoma [ Oncol Rep, 2023, 50(3)167] | PubMed: 37477142 |
| Zoledronic Acid Inhibits the Growth of Breast Malignant Phyllodes Tumor by Inducing Mitotic Catastrophe Via the Plk1 Signaling Pathway [ SSRN, 2023, 38 Pages] | PubMed: none |
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。