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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
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Synonyms | HKI-272 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C30H29ClN6O3 |
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| 分子量 | 557.04 | CAS No. | 698387-09-6 | |
| Solubility (25°C)* | 体外 | DMSO | 6 mg/mL (10.77 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 | Neratinibは、無細胞アッセイにおいてIC50が59 nMおよび92 nMである、高選択的なHER2およびEGFR阻害剤です。KDRおよびSrcを弱く阻害し、Akt、CDK1/2/4、IKK-2、MK-2、PDK1、c-Raf、c-Metに対して有意な阻害はありません。フェーズ3。 |
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| in vitro | Neratinib weakly inhibits tyrosine kinases KDR and Src with IC50 of 0.8 μM and 1.4 μM, respectively, being 14- and 24-fold less active compared with HER2. This compound displays no activity against other serine-threonine kinases such as Akt, cyclin D1/cdk4, cyclin E/cdk2, cyclin B1/cdk1, IKK-2, MK-2, PDK1, c-Raf, and Tpl-2, as well as the tyrosine kinase c-Met. It selectively inhibits the proliferation of 3T3 cells transfected with the HER2 (3T3/neu), as well as two other HER-2-overexpressing SK-Br-3 and BT474 cells with IC50 values of 2-3 nM, displaying >230-fold potency compared with non-transfected 3T3 cells as well as MDA-MB-435 and SW620 which are EGFR- and HER2-negative. This chemical also inhibits the proliferation of EGFR-dependent A431 cells with an IC50 of 81 nM. It reduces HER2 receptor autophosphorylation in BT474 cells with an IC50 of 5 nM, and EGF-dependent phosphorylation of EGFR in A431 cells with IC50 of 3 nM. Blocking of HER-2 by this compound results in inhibition of downstream MAPK and Akt pathways with IC50 of 2 nM, more potently than Trastuzumab. It inhibits the cyclin D1 expression and the phosphorylation of the Rb-susceptibility gene production in BT474 cells with IC50 of 9 nM, leading to G1-S arrest and ultimately decreased cell proliferation. |
| in vivo | Oral administration of Neratinib significantly inhibits the growth of 3T3/neu xenografts, with inhibition of 34%, 53%, 98%, and 98% at dose of 10, 20, 40, and 80 mg/kg/day, respectively. Consistent with the inhibition of HER-2 phosphorylation by 84% within 1 hour of administration at 40 mg/kg/day, this compound inhibits the growth of BT474 xenografts by 70-82%, 67%, and 93% at dose of 5, 10, and 40 mg/kg/day, respectively. It is also effective against SK-OV-3 xenografts with inhibition of 31% and 85% at 5 and 60 mg/kg/day, respectively. This chemical is less potent against EGFR-dependent A431 xenografts than HER-2-dependent tumors, with 32% and 44% inhibition at 5 and 20 mg/kg/day, respectively. It displays little activity against MCF-7 and MX-1 xenografts expressing low levels of HER-2 and EGFR, with only 28% inhibition at 80 mg/kg/day, suggesting that it has selective activity for cells expressing HER-2 or EGFR. |
プロトコル(参考用のみ)
| キナーゼアッセイ | Cell-free autophosphorylation assay using time-resolved fluorometry | |
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| Neratinib is prepared as 10 mg/mL stocks in DMSO and diluted in 25 mM HEPES (pH 7.5; 0.002 ng/mL-20 μg/mL). Purified recombinant COOH-terminal fragments of HER2 (amino acids 676-1255) or epidermal growth factor receptor (EGFR) (amino acids 645-1186) [diluted in 100 mM HEPES (pH 7.5) and 50% glycerol] is incubated with increasing concentrations of this compound in 4 mM HEPES (pH 7.5), 0.4 mM MnCl2, 20 μM sodium vanadate, and 0.2 mM DTT for 15 minutes at room temperature in 96-well ELISA plates. The kinase reaction is initiated by the addition of 40 μM ATP and 20 mM MgCl2 and allowed to proceed for 1 hour at room temperature. Plates are washed, and phosphorylation is detected using Europium-labeled anti-phospho-tyrosine antibodies (15 ng/well). After washing and enhancement steps, signal is detected using a Victor2 fluorescence reader (excitation wavelength 340 nm, emission wavelength 615 nm). The concentration of this chemical that inhibits receptor phosphorylation by 50% (IC50) is calculated from inhibition curves. | ||
| 細胞アッセイ | 細胞株 | 3T3, 3T3/neu, A431, BT474, SK-Br-3, MDA-MB-435, and SW480 |
| 濃度 | Dissolved in DMSO, final concentrations 0.5 ng/mL-5 μg/mL | |
| 反応時間 | 2 or 6 days | |
| 実験の流れ | Cells are exposed to various concentrations of Neratinib for 2, or 6 days. Cell proliferation is determined using sulforhodamine B, a protein binding dye. Briefly, cells are fixed with 10% trichloroacetic acid and washed extensively with water. Cells are then stained with 0.1% sulforhodamine B and washed in 5% acetic acid. Protein-associated dye is solubilized in 10 mM Tris, and absorbance is measured at 450 nM. The concentration of this compound that inhibits cell proliferation by 50% (IC50) is determined from inhibition curves. | |
| 動物実験 | 動物モデル | Female athymic (nude) mice implanted s.c. with 3T3/neu, BT474, MCF-7, or SK-OV-3 cells |
| 投薬量 | ~80 mg/kg/day | |
| 投与方法 | 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 [Cancer Discov, 2013, 3, 224-37]
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Data from [Cancer Discov, 2012, 2, 458-471]
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Data from [Cancer Discov, 2012, 2, 458-471]
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：
| APOBEC3 mutagenesis drives therapy resistance in breast cancer [ Nat Genet, 2025, 57(6):1452-1462] | PubMed: 40379787 |
| Sevabertinib, a Reversible HER2 Inhibitor with Activity in Lung Cancer [ Cancer Discov, 2025, 10.1158/2159-8290.CD-25-0605] | PubMed: 41090369 |
| Small molecule kinase inhibitor altiratinib inhibits brain cyst forming bradyzoites of Toxoplasma gondii [ J Microbiol, 2025, 63(2):e2409001] | PubMed: 40044130 |
| KinoViz: A User-Friendly Web Application for High-Throughput Kinome Profiling Analysis and Visualization in Cancer Research [ Res Sq, 2025, rs.3.rs-6431257] | PubMed: 40630533 |
| Hotspot mutations in HER2 interfaces destabilize structure, causing breast cancer treatment failure [ Res Sq, 2025, rs.3.rs-5931887] | PubMed: 40166021 |
| Proteogenomic analysis dissects early-onset breast cancer patients with prognostic relevance [ Exp Mol Med, 2024, 56(11):2382-2394] | PubMed: 39482530 |
| Peptidylarginine deiminase 3 modulates response to neratinib in HER2 positive breast cancer [ Oncogenesis, 2024, 13(1):30] | PubMed: 39097594 |
| Patient-derived rhabdomyosarcoma cells recapitulate the genetic and transcriptomic landscapes of primary tumors [ iScience, 2024, 27(10):110862] | PubMed: 39319271 |
| Synergistic Effects of Neratinib in Combination With Palbociclib or Miransertib in Brain Cancer Cells [ World J Oncol, 2024, 15(3):492-505] | PubMed: 38751701 |
| The Combination of Afatinib With Dasatinib or Miransertib Results in Synergistic Growth Inhibition of Stomach Cancer Cells [ World J Oncol, 2024, 15(2):192-208] | PubMed: 38545471 |
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。