Orelabrutinib
(Synonyms: 奥布替尼,ICP-022) 目录号 : GC39634
Orelabrutinib是一种口服给药的强效、不可逆、高选择性BTK抑制剂，IC50值为1.6nM。
Cas No.:1655504-04-3
Sample solution is provided at 25 µL, 10mM.
Orelabrutinib is an orally administered, potent, irreversible and highly selective BTK-inhibitor with an IC50 value of 1.6nM[1]. Orelabrutinib can reduce the expression of BTK and Mcl-1, and interfere with the activities of the PI3K/AKT signaling pathway and the p38/MAPK signaling pathway[2]. Orelabrutinib has been widely used in mouse models to treat primary immune thrombocytopenia (ITP)[3].
In vitro, Orelabrutinib treatment for 72h significantly inhibited the viability of TMD8 cells, HBL-1 cells and SU-DHL-6 cells with IC50 values of 0.03μM, 0.17μM, and 1.89μM, respectively[4]. Treatment of SU-DHL-4 cells with 60μM Orelabrutinib combined with 2.5μM Chidamide for 48 hours significantly promoted cell apoptosis and induced cell cycle arrest[5]. Treatment with 2μM Orelabrutinib combined with 1μM Selinexor for 48 hours strongly inhibited the NF-κB, P-STAT3 and NFATc1 signaling pathways in OCI-LY10 cells and OCI-LY3 cells[6].
In vivo, Orelabrutinib treatment via oral administration at a dose of 10mg/kg/day for 28 days remarkablely reduced platelet phagocytosis and pro-inflammatory cytokine production in ITP mice[7]. In the TMD8 cell xenograft tumor mouse model, daily oral administration of 10mg/kg dose of Orelabrutinib for 3 weeks significantly inhibited tumor growth[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.
Orelabrutinib是一种口服给药的强效、不可逆、高选择性BTK抑制剂，IC50值为1.6nM[1]。Orelabrutinib可降低BTK和Mcl-1的表达，并干扰PI3K/AKT信号通路和p38/MAPK信号通路的活性[2]。Orelabrutinib已广泛用于小鼠模型，以治疗原发性免疫性血小板减少症(ITP)[3]。
在体外，Orelabrutinib处理72小时显著抑制了TMD8细胞、HBL-1细胞和SU-DHL-6细胞的活力，其IC50值分别为0.03μM、0.17μM和1.89μM[4]。用60μM的Orelabrutinib联合2.5μM的Chidamide处理SU-DHL-4细胞48小时，显著促进了细胞凋亡并诱导细胞周期停滞[5]。用2μM的Orelabrutinib联合1μM塞利尼索处理OCI-LY10细胞和OCI-LY3细胞48小时，强烈抑制了NF-κB、P-STAT3和NFATc1信号通路[6]。
在体内，以10mg/kg/day的剂量口服给予Orelabrutinib治疗28天，显著减少了ITP小鼠的血小板吞噬和促炎细胞因子产生[7]。在TMD8细胞异种移植瘤小鼠模型中，每日口服10mg/kg剂量的Orelabrutinib，持续3周，显著抑制了肿瘤生长[4]。
| Cell experiment [1]: | |
Cell lines | TMD8 cells |
Preparation Method | TMD8 cells were cultured using RPMI-1640 medium containing 10% fetal bovine serum (FBS), penicillin/streptomycin, glutamine and β-mercaptoethanol, in a humidified environment of a 37°C, 5% CO2 incubator. A 90μl inoculum of cells at a concentration of 5×104/ml was seeded in a 96-well black-bottom plate and incubated with different concentrations of Orelabrutinib (0, 0.1, 1, 2, and 4μM) for 72 hours. The plate was incubated at room temperature on a shaker for 10 minutes, and cell viability was determined using MTT assay. |
Reaction Conditions | 0, 0.1, 1, 2, and 4μM; 72h |
Applications | Orelabrutinib treatment inhibited the proliferation of TMD8 cells in a concentration-dependent manner. |
| Animal experiment [2]: | |
Animal models | Severe combined immunodeficient (SCID) mice |
Preparation Method | The 5×104 splenocytes from immunized CD61-knockout mice against CD61+ platelets were engrafted into CD61+ SCID mice to establish active ITP models, which exhibited profound thrombocytopenia. The ITP mice were divided into the Orelabrutinib group, which was given Orelabrutinib dissolved in 0.5% CMC-Na (10mg/kg) by intragastric administration once daily, and the control group was given 0.5% CMC-Na. The experiment lasted for 28 days, and the platelet counts and inflammatory factors of the mice were analyzed. |
Dosage form | 10mg/kg/day for 28 days; p.o. |
Applications | Orelabrutinib treatment significantly enhanced platelet counts and reduced serum concentrations of IL-6 and IL-1β in ITP mice. |
References: | |
| Cas No. | 1655504-04-3 | SDF | |
| 别名 | 奥布替尼,ICP-022 | ||
| Canonical SMILES | O=C(C1=CC=C(C2CCN(C(C=C)=O)CC2)N=C1C3=CC=C(OC4=CC=CC=C4)C=C3)N | ||
| 分子式 | C26H25N3O3 | 分子量 | 427.5 |
| 溶解度 | DMSO: 250 mg/mL (584.80 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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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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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
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2.
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- Purity: >98.50%
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