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受注：045-509-1970 |
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化学情報
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Synonyms | MSC1936369B, SAR 245509 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C15H15FIN3O3 |
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| 分子量 | 431.20 | CAS No. | 1236699-92-5 | |
| Solubility (25°C)* | 体外 | DMSO | 86 mg/mL (199.44 mM) | |
| Ethanol | 1 mg/mL (2.31 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 | Pimasertib (AS-703026, MSC1936369B, SAR 245509) is a highly selective, potent, ATP non-competitive allosteric inhibitor of MEK1/2 with IC50 of 5 nM-2 μM in MM cell lines. Phase 2. |
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| in vitro | AS703026 is a novel, selective, orally bioavailable MEK1/2 inhibitor that binds to the distinctive MEK allosteric site and therefore exhibits exquisite kinase selectivity. AS703026 inhibits growth and survival of human multiple myeloma (MM) cells, including U266 and INA-6, with IC50 of 5 nM and 11 nM, respectively. Such an inhibitory effect by AS703026 is mediated by G0-G1 cell cycle arrest and is accompanied by reduced expresson of the MAF oncogene. AS703026 further induces apoptosis via caspase-3 and PARP cleavage in MM cells, both in the presence or absence of bone marrow stromal cells (BMSCs). [1] AS703026 may be an effective therapy in colorectal cancer caused by K-Ras mutation. AS703026 (10 μM) effectively inhibits the ERK pathway, proliferation, and transformation in human DLD-1 colorectal cancer cells what carry a mutant allele of K-Ras (D-MUT). [2] |
| in vivo | AS703026 (15 and 30 mg/kg) significantly inhibits tumor growth in a human plasmacytoma xenograft model of H929 MM cells. This can be correlated with downregulated pERK1/2, induced PARP cleavage, and decreased microvessels. [1] AS703026 (10 mg/kg) inhibits tumor growth, and markedly decreases p-ERK level in a xenograft mouse model of human K-Ras mutated (D-MUT) colorectal tumor. [2] |
| 特徴 | A novel, highly selective and potent allosteric inhibitor of MEK1/2. |
プロトコル(参考用のみ)
| キナーゼアッセイ | MEK1 enzyme assays | |
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| AS703026 is dissolved in 2.5% DMSO. Activated diphosphorylated MEK (pp-MEK) assays contained 40 μM 33P-γATP (AppKm 8.5 μM), 0.5 nM human-activated MEK1 or MEK2, 1 μM kinase-dead ERK2 (AppKm 0.73 μM). All assays are done in buffer containing 20 mM HEPES (pH 7.2), 5 mM 2-mercaptoethanol, 0.15 mg/mL BSA, and 10 mM MgCl2. The final concentration of 33P- ATP is 0.02 μCi/μL for all the assays. pp-MEK kinase reactions are stopped after 40 min by transferring 30 μL of reaction mixture to Durapore 0.45-μm filters plates containing 12.5% TCA. Filters are dried and read with liquid scintilant on a TopCount. Concentration response data are analyzed for IC50. 0.2 nM recombinant human MEK1 or MEK2 is preincubated with vehicle or with AS703026 for 40 minutes in reaction buffer to determine IC50 of initially unphosphorylated MEK (u-MEK). Phosphorylation/activation is initiated by the addition of a final concentration of 20 nM final B-RafV600E and 30 μM final ATP for 10 min. B-Raf activity is then quenched by addition of the B-Raf inhibitor SB590885 (final concentration 100 nM), and MEK kinase activity is assayed by the addition of 1 μM KD-ERK2 and 0.02 μCi/μL 33P-ATP in reaction buffer. The kinase reactions are stopped after 90 min by transferring 30μL of reaction mixture to a Durapore filter plate, and read as above. | ||
| 細胞アッセイ | 細胞株 | U266 and INA-6 cells |
| 濃度 | 2 nM - 20 μM (stock: 10 mM in DMSO) | |
| 反応時間 | 48 hours | |
| 実験の流れ | Cytotoxicity assays for AS703026 are assessed by measuring both [3H]thymidine incorporation and MTT dye absorbance. Cells (1 × 104 per well) are cultured in 96-well plates for 3 days. For the [3H]thymidine incorporation assay, cells are pulsed with 18.5 kBq/well [3H]thymidine for 6 hours, harvested onto glass fibre filters, and counted in a β-scintillation counter. Cell cycle analysis is assessed by propidium iodide (PI) staining using flow cytometry. AS703026-induced apoptosis is determined by annexin-V/PI staining and flow cytometric data analysis. | |
| 動物実験 | 動物モデル | H929 MM xenografts are established in CB17 (SCID) mice |
| 投薬量 | 15 or 30 mg/kg | |
| 投与方法 | Oral gavage twice daily | |
参考
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カスタマーフィードバック
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Data from [Data independently produced by FASEB J, 2014, 10.1096/fj.13-247924]
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Data from [Data independently produced by Endocrinology, 2013, 154(9), 3219-27]
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, , Dr. Zhang of Tianjin Medical University
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：
| ATP1A1 is a promising new target for melanoma treatment and can be inhibited by its physiological ligand bufalin to restore targeted therapy efficacy [ Cancer Cell Int, 2024, 24(1):8] | PubMed: 38178183 |
| Salmonella effector SopB reorganizes cytoskeletal vimentin to maintain replication vacuoles for efficient infection [ Nat Commun, 2023, 14(1):478] | PubMed: 36717589 |
| ETS1 phosphorylation at threonine 38 is associated with the cell of origin of diffuse large B cell lymphoma and sustains the growth of tumour cells [ Br J Haematol, 2023, 10.1111/bjh.19018] | PubMed: 37584198 |
| Three generations of mTOR kinase inhibitors in the activation of the apoptosis process in melanoma cells [ J Cell Commun Signal, 2023, 17(3):975-989] | PubMed: 37097377 |
| A Cell Cycle-Dependent Ferroptosis Sensitivity Switch Governed by EMP2 [ bioRxiv, 2023, 2023.07.19.549715] | PubMed: 37502927 |
| Anatomic position determines oncogenic specificity in melanoma [ Nature, 2022, 604(7905):354-361] | PubMed: 35355015 |
| Identification of New Vulnerabilities in Conjunctival Melanoma Using Image-Based High Content Drug Screening [ Cancers (Basel), 2022, 14(6)1575] | PubMed: 35326726 |
| Mcl-1 and Bcl-xL levels predict responsiveness to dual MEK/Bcl-2 inhibition in B-cell malignancies [ Mol Oncol, 2021, 10.1002/1878-0261.13153] | PubMed: 34861096 |
| Pharmacologically controlling protein-protein interactions through epichaperomes for therapeutic vulnerability in cancer [ Commun Biol, 2021, 4(1):1333] | PubMed: 34824367 |
| Tyrosine-Dependent Phenotype Switching Occurs Early in Many Primary Melanoma Cultures Limiting Their Translational Value [ Front Oncol, 2021, 11:780654] | PubMed: 34869032 |
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。