Orelabrutinib |
カタログ番号GC39634
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Orelabrutinibは経口投与で、有力で、不可逆的で高い選択性を持つBTK阻害剤であり、IC50値は1.6nMである。
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Cas No.: 1655504-04-3
Sample solution is provided at 25 µL, 10mM.
Orelabrutinibは経口投与で、有力で、不可逆的で高い選択性を持つBTK阻害剤であり、IC50値は1.6nMである[1]。Orelabrutinibは、BTKとMcl-1の発見を減らし、PI3K/AKTシグナル伝達経路とp38/MAPKシグナル伝達経路の活性を干渉する[2]。Orelabrutinibはマウスモデルに広く使われ、原発性免疫血小板減少症（ITP）を治療する[3]。
体外で、Orelabrutinibで72時間処理した結果、TMD8細胞、HBL-1細胞とSU-DHL-6細胞の生存率を著しく阻害し、IC50値はそれぞれ0.03μM、0.17μMと1.89μMである[4]。60μMのOrelabrutinibと2.5μMのChidamideを併用してSU-DHL-4細胞を48時間処理した結果、細胞のアポトーシスを著しく促進し、細胞周期停止を誘発した[5]。2μMのOrelabrutinibと1μMのSelinexorで48時間併用処理した結果、OCI-LY10細胞とOCI-LY3細胞で、NF-κB、P-STAT3とNFATc1シグナル伝達経路を強く阻害した[6]。
体内で、10mg/kg/日のOrelabrutinibを28日間経口投与した結果、ITPマウスで、血小板の食作用と炎症促進のサイトカインの産生を著しく減らした[7]。TMD8細胞異種移植腫瘍マウスモデルで、10mg/kgのOrelabrutinibを3週間、毎日経口投与した結果、腫瘍の成長を著しく阻害した[4]。
References:
[1] Zhang B, Zhao R, Liang R, et al. Abstract CT132: Orelabrutinib, a potent and selective Bruton's tyrosine kinase inhibitor with superior safety profile and excellent PK/PD properties[J]. Cancer Research, 2020, 80(16_Supplement): CT132-CT132.
[2] Pan G, Zhong M, Yao J, et al. Orelabrutinib and venetoclax synergistically induce cell death in double-hit lymphoma by interfering with the crosstalk between the PI3K/AKT and p38/MAPK signaling[J]. Journal of cancer research and clinical oncology, 2023, 149(9): 5513-5529.
[3] Yu T, Wang L, Ni X, et al. Orelabrutinib, a selective Bruton's tyrosine kinase (BTK) inhibitor in the treatment of primary immune thrombocytopenia (ITP)[J]. Blood, 2021, 138: 3172.
[4] Yu H, Wang X, Li J, et al. Addition of BTK inhibitor orelabrutinib to rituximab improved anti-tumor effects in B cell lymphoma[J]. Molecular Therapy-Oncolytics, 2021, 21: 158-170.
[5] Wu C, Chen S, Wu Z, et al. Chidamide and orelabrutinib synergistically induce cell cycle arrest and apoptosis in diffuse large B-cell lymphoma by regulating the PI3K/AKT/mTOR pathway[J]. Journal of Cancer Research and Clinical Oncology, 2024, 150(2): 98.
[6] Li L, Yang W, Ye R, et al. Combination of Selinexor with BTK Inhibitor for Central Nervous System Diffuse Large B-Cell Lymphoma, Possible Mechanisms and Therapeutic Potential Exploration[J]. Blood, 2023, 142: 3010.
[7] Yu T, Han S, Wang L, et al. Effects of orelabrutinib, a BTK inhibitor, on antibody‐mediated platelet destruction in primary immune thrombocytopenia[J]. British Journal of Haematology, 2025, 206(4): 1186-1199.
| 細胞実験[1]: | |
細胞株 | TMD8細胞 |
準備方法 | 37°C、5% CO2のインキュベーター（加湿環境）で、10%のウシ胎児血清（FBS）、ペニシリン/ストレプトマイシン、グルタミン酸とβ-メルカプトエタノールを含有するRPMI-1640培地でTMD8細胞を培養した。5×104/mlの濃度、90μlの細胞接種液を96ウェルの黒底のプレートに播種し、様々な濃度のOrelabrutinib（0、0.1、1、2と4μM）で72時間インキュベートした。室温、プレートをシェーカーで10分間インキュベートし、細胞の生存率をMTT法で測定した。 |
反応条件 | 0、0.1、1、2と4μM；72時間 |
アプリケーション | Orelabrutinibの処理は、TMD8細胞の増殖を濃度依存的に阻害した。 |
| 動物実験 [2]: | |
動物モデル | 重症複合免疫不全症（SCID）のマウス |
準備方法 | CD61+血小板に対する免疫化のCD61ノックアウトマウスからの5×104個の脾細胞を、CD61+ SCIDマウスに移植し、活性なITPモデルを作成し、重度の血小板減少症を示した。ITPマウスを分け、Orelabrutinib群には、0.5%のCMC-Na（10mg/kg）に溶解されたOrelabrutinibを毎日一回胃内投与し、対照群には0.5%のCMC-Naを投与した。実験は28日間続き、マウスの血小板の数と炎症因子を分析した。 |
投与形態 | 10mg/kg/日、28日間；経口投与 |
アプリケーション | Orelabrutinibの処理は、ITPマウスで、血小板の数を著しく増やし、IL-6とIL-1βの血清濃度を減らした。 |
References: | |
| Cas No. | 1655504-04-3 | SDF | |
| Canonical SMILES | O=C(C1=CC=C(C2CCN(C(C=C)=O)CC2)N=C1C3=CC=C(OC4=CC=CC=C4)C=C3)N | ||
| Formula | C26H25N3O3 | M.Wt | 427.5 |
| 溶解度 | DMSO: 250 mg/mL (584.80 mM) | 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 | 2.3392 mL | 11.6959 mL | 23.3918 mL |
| 5 mM | 467.8 μL | 2.3392 mL | 4.6784 mL |
| 10 mM | 233.9 μL | 1.1696 mL | 2.3392 mL |
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Quality Control & SDS
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- Purity: >98.50% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 34 reference(s) in Google Scholar.)