R428 (Synonyms: R-428;R 428;BGB324) |
カタログ番号GC17618
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R428はAxlの阻害剤としてナノモル濃度でAxl C末端のドッキングサイトのTyr821における自己リン酸化を遮断できる。
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Cas No.: 1037624-75-1
Sample solution is provided at 25 µL, 10mM.
R428はAxlの阻害剤としてナノモル濃度でAxl C末端のドッキングサイトのTyr821における自己リン酸化を遮断できる[1]。
体外ではR428用量依存的な方法でH1299の成長を阻害し、IC50の値は約4µMである[1]。CE81T細胞では処理の72時間後のR428のIC50の値は1.98µMである[2]。体外ではTNBC細胞を0.5、1または2µMのR428でそれぞれ30分間、1、2、4時間処理し、移動細胞におけるゴルジ体前縁の分極局在を破壊した[3]。
体内ではラットに体重100mg/kg（経口投与）のR428を投与し、結果によって、よりひどいRV肥厚、右心室収縮期血圧(RVSP)の上昇、心臓出力の障害、三尖弁環面収縮期オフセットの悪化および肺血管総量の抵抗指数の有意な増加を示す[4]。体内薬効テストによると、R428はすごし長い血漿半減期（75mg/kgでは13時間）を持っているが、組織に有効的に分布できる[5]
体内では腎臓病B6鼠の腎臓中のT細胞数と比べると、R428を125mg/kg経口投与した鼠（8週齢）の腎臓におけるCD4+T細胞数が顕著に減少する[6]。
References:
[1] Chen F, et al. Axl inhibitor R428 induces apoptosis of cancer cells by blocking lysosomal acidification and recycling independent of Axl inhibition. Am J Cancer Res. 2018 Aug 1;8(8):1466-1482.
[2] Yang PW, et al. Cabozantinib (XL184) and R428 (BGB324) Inhibit the Growth of Esophageal Squamous Cell Carcinoma (ESCC). Front Oncol. 2019 Nov 6;9:1138.
[3] Zajac O, et al. AXL Controls Directed Migration of Mesenchymal Triple-Negative Breast Cancer Cells. Cells. 2020 Jan 19;9(1):247.
[4] Novoyatleva T, et al. Deficiency of Axl aggravates pulmonary arterial hypertension via BMPR2. Commun Biol. 2021 Aug 24;4(1):1002. doi: 10.1038/s42003-021-02531-1. Erratum in: Commun Biol. 2022 Jan 20;5(1):97.
[5] Zhen Y, et al. Targeted inhibition of Axl receptor tyrosine kinase ameliorates anti-GBM-induced lupus-like nephritis. J Autoimmun. 2018 Sep;93:37-44.
[6] Zhen Y, et al. Axl regulated survival/proliferation network and its therapeutic intervention in mouse models of glomerulonephritis. Arthritis Res Ther. 2022 Dec 28;24(1):284.
| 細胞実験[1]: | |
細胞株 | B-CPAP細胞株（ヒトのPTC癌組織由来） |
準備方法 | B-CPAP細胞株を培養し、、異なる濃度（0.5µmol/L、1µmol/L、2µmol/L、4µmol/L）AXLの阻害剤であるR428をで処理し、未処理のB-CPAP細胞株を対照群として観察する。CCK-8を測定することで細胞増殖を評価する。 |
反応条件 | 0.5μmol/L、1μmol/L、2μmol/L、4μmol/L; 24時間 |
アプリケーション | B-CPAP実験群は0.5、1.0、2.0、4.0µmol/LのR428が処理した細胞の生存率はそれぞれ85.28%±9.21%、66.74%±3.88%、41.51%±6.33%、3.71%±それぞれ2.10%である。 |
| 動物実験 [2]: | |
動物モデル | NOD-SCIDオス鼠 |
準備方法 | 動物のモデルではNOD-SCIDオス鼠の上背部にKYSE-70細胞をマトリックゲルとともに注射すし、キャリアによる対照R428（50mg/kg/日）で治療することにより、ESCC（食道扁平上皮癌）異種移植モデル。)シスプラチン(1.0mg/kg)又はカボチニブ(30mg/kg/日)を設立し、指定された日数を続く。 |
投与形態 | 50 mg/kg/day; i.p. |
アプリケーション | ベクターと比べると、、R428単独はESCC腫瘍の成長を有顕著に阻害するが、シスプラチンとの相乗効果は観察されていない。 |
References: | |
| Cas No. | 1037624-75-1 | SDF | |
| 同義語 | R-428;R 428;BGB324 | ||
| Chemical Name | 1-(6,7-dihydro-5H-benzo[2,3]cyclohepta[2,4-d]pyridazin-3-yl)-3-N-[(7S)-7-pyrrolidin-1-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]-1,2,4-triazole-3,5-diamine | ||
| Canonical SMILES | C1CCN(C1)C2CCC3=C(CC2)C=C(C=C3)NC4=NN(C(=N4)N)C5=NN=C6C(=C5)CCCC7=CC=CC=C76 | ||
| Formula | C30H34N8 | M.Wt | 506.64 |
| 溶解度 | ≥ 25mg/mL in DMSO with gentle warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9738 mL | 9.8689 mL | 19.7379 mL |
| 5 mM | 394.8 μL | 1.9738 mL | 3.9476 mL |
| 10 mM | 197.4 μL | 986.9 μL | 1.9738 mL |
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Quality Control & SDS
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- Purity: >99.00% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 6 reference(s) in Google Scholar.)