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受注：045-509-1970 |
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化学情報
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Synonyms | LY317615 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C32H29N5O2 |
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| 分子量 | 515.61 | CAS No. | 170364-57-5 | |
| Solubility (25°C)* | 体外 | DMSO | 30 mg/mL (58.18 mM) | |
| Water | Insoluble | |||
| Ethanol | 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 | Enzastaurin is a potent PKCβ selective inhibitor with IC50 of 6 nM in cell-free assays, 6- to 20-fold selectivity against PKCα, PKCγ and PKCε. Phase 3. |
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| in vitro | Enzastaurin application results in a marked dose-dependent inhibition of growth in all MM cell lines investigated, including MM.1S, MM.1R, RPMI 8226 (RPMI), RPMI-Dox40 (Dox40), NCI-H929, KMS-11, OPM-2, and U266, with IC50 from 0.6-1.6 μM. Enzastaurin direct impacts human tumor cells, inducing apoptosis and suppressing proliferation in cultured tumor cells. Enzastaurin also suppresses the phosphorylation of GSK3βser9, ribosomal protein S6S240/244, and AKTThr308 while having no direct effect on VEGFR phosphorylation. [1] Enzastaurin increases apoptosis in malignant lymphocytes of CTCL. When combined with GSK3 inhibitors, enzastaurin demonstrated an enhancement of cytotoxicity levels. Treatment with a combination of enzastaurin and the GSK3 inhibitor AR-A014418 led to increased levels of β-catenin total protein and β-catenin-mediated transcription. Blocking of β-catenin-mediated transcription or small hairpin RNA (shRNA) knockdown of β-catenin induced the same cytotoxic effects as that of enzastaurin plus AR-A014418. Additionally, treatment with enzastaurin and AR-A014418 decreased the mRNA levels and surface expression of CD44. [2] |
| in vivo | Treatment of xenografts with Enzastaurin and radiation produced greater reductions in density of microvessels than either treatment alone. The decrease in microvessel density corresponded to delayed tumor growth. [3] |
プロトコル(参考用のみ)
| キナーゼアッセイ | Kinase inhibition assays | |
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| The inhibition of PKCβII, PKCα, PKCε, or PKCγ activity by enzastaurin is determined using a filter plate assay format measuring 33P incorporation into myelin basic protein substrate. Reactions are done in 100 μL reaction volumes in 96-well polystyrene plates with final conditions as follows: 90 mM HEPES (pH 7.5), 0.001% Triton X-100, 4% DMSO, 5 mM MgCl2, 100 μM CaCl2, 0.1 mg/mL phosphatidylserine, 5 μg/mL diacetyl glyerol, 30 μM ATP, 0.005 μCi/μL 33ATP, 0.25 mg/mL myelin basic protein, serial dilutions of enzastaurin (1-2,000 nM), and recombinant human PKCβII, PKCα, PKCε, or PKCγ enzymes (390, 169, 719, or 128 pM, respectively). Reactions are started by addition of the enzyme and incubated at room temperature for 60 minutes. They are then quenched with 10% H3PO4, transferred to multiscreen anionic phosphocellulose 96-well filter plates, incubated for 30 to 90 minutes, filtered and washed with 4 volumes of 0.5% H3PO4 on a vacuum manifold. Scintillation cocktail is added and plates are read on a Microbeta scintillation counter. IC50 values are determined by fitting a three-variable logistic equation to the 10-point dose-response data using ActivityBase 4.0. | ||
| 細胞アッセイ | 細胞株 | HCT116 and U87MG cells |
| 濃度 | 0.3-4 μM | |
| 反応時間 | 72 hours | |
| 実験の流れ | Induction of apoptosis by enzastaurin is measured by nucleosomal fragmentation and terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) and staining in HCT116 and U87MG cell lines. Briefly, 5 × 103 cells are plated per well in 96-well plates (1% FBS-supplemented media conditions), incubated with or without Enzastaurin for 48 to 72 hours. The absorbance values are normalized to those from control-treated cells to derive a nucleosomal enrichment factor at all concentrations as per the manufacturer's protocol. The concentrations studied ranges from 0.1 to 10 μM. In situ TUNEL staining is assayed with the In situ Cell Death Detection, Fluorescein kit. Cells (7.5 ?104) are plated per well in 6-well plates and incubated 72 hours in 1% FBS-supplemented media ?Enzastaurin. Fluorescein-labeled DNA strand breaks are detected with the BD epics flow cytometer. Ten thousand, single-cell, FITC-staining events are collected for each test. |
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| 動物実験 | 動物モデル | Athymic nude mice; Mouse besring human MM tumors |
| 投薬量 | 75 mg/kg twice daily; 30 mg/kg twice daily | |
| 投与方法 | By gavage | |
参考
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カスタマーフィードバック
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Data from [Arthritis Rheum, 2013, 65, 1022-31]
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Data from [Arthritis Rheum, 2013, 65, 1022-31]
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Data from [J Biol Chem, 2011, 286, 39760-7]
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：
| PKCβII phosphorylates ACSL4 to amplify lipid peroxidation to induce ferroptosis [ Nat Cell Biol, 2022, 24(1):88-98] | PubMed: 35027735 |
| Targeting a splicing-mediated drug resistance mechanism in prostate cancer by inhibiting transcriptional regulation by PKCβ1 [ Oncogene, 2022, 10.1038/s41388-022-02179-z] | PubMed: 35087237 |
| Inhibition of IκB Kinase Is a Potential Therapeutic Strategy to Circumvent Resistance to Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer Cells [ Cancers (Basel), 2022, 14(21)5215] | PubMed: 36358633 |
| Establishment and characterization of immortalized sweat gland myoepithelial cells [ Sci Rep, 2022, 12(1):7] | PubMed: 34997030 |
| Amphetamine-induced neurite injury in PC12 cells through inhibiting GAP-43 pathway [ Neurotoxicology, 2022, 93:103-111] | PubMed: 36150536 |
| Reversible phosphorylation of cyclin T1 promotes assembly and stability of P-TEFb [ Elife, 2021, 10e68473] | PubMed: 34821217 |
| P2X7 Receptor Deficiency Ameliorates STZ-induced Cardiac Damage and Remodeling Through PKCβ and ERK [ Front Cell Dev Biol, 2021, 9:692028] | PubMed: 34395424 |
| High-content image-based analysis and proteomic profiling identifies Tau phosphorylation inhibitors in a human iPSC-derived glutamatergic neuronal model of tauopathy [ Sci Rep, 2021, 11(1):17029] | PubMed: 34426604 |
| mTORC2 Activation Mediated by Mesenchymal Stem Cell-Secreted Hepatocyte Growth Factors for the Recovery of Lipopolysaccharide-Induced Vascular Endothelial Barrier [ Stem Cells Int, 2021, 2021:9981589] | PubMed: 34707661 |
| Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells [ Cell, 2020, S0092-8674(20)31394-5] | PubMed: 33147445 |
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。