Tirabrutinib (ONO-4059) hydrochloride 是一种口服有效的高选择性Bruton’s Tyrosine Kinase(BTK) 抑制剂 (能透过血脑屏障)，其IC50值为 6.8 nM。Tirabrutinib hydrochloride 不可逆共价结合BTK并抑制异常 B 细胞受体信号传导。Tirabrutinib hydrochloride 可用于自身免疫性疾病和血液学恶性肿瘤的研究。
| 生物活性 | Tirabrutinib (ONO-4059) hydrochloride is an orally activeBruton’s Tyrosine Kinase(BTK) inhibitor (can cross the blood-brain barrier (BBB)), with anIC50of 6.8 nM. Tirabrutinib hydrochloride irreversibly and covalently binds toBTKand inhibits aberrant B cell receptor signaling. Tirabrutinib hydrochloride can be used in studies of autoimmune diseases and hematological malignancies[1][2][3][4]. |
| IC50& Target | BMX 6 nM (IC50) | BTK 6.8 nM (IC50) | TEC 48 nM (IC50) | TXK 92 nM (IC50) | BLK 0.3 μM (IC50) | ERBB4 0.77 μM (IC50) | EGFR 3.02 μM (IC50) | JAK3 5.52 μM (IC50) | ERBB2 7.31 μM (IC50) |
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体外研究
(In Vitro) | Tirabrutinib hydrochloride (0.1-1000 nM or 0.001-100 nM; 72 h) inhibits the proliferation of OCI-L Y10 and SU-DHL-6 cells with IC50s of 9.127 nM, and 17.10 nM, respectively[1].
Tirabrutinib hydrochloride (0.5, 5, 50 μM; 24, 48 h) induces SU-DHL-6 cells apoptosis needs high dosage and prolonged administration (concentration up to 50 μM and incubates for 48 h)[1].
Tirabrutinib hydrochloride (300 nM, 72 h) induces caspase-3 and PARP cleavage in TMD8 cells[2].
Cell Proliferation Assay[1] | Cell Line: | SU-DHL-6 and OCI-L Y10 cells | | Concentration: | 0.1-1000 nM; 0.001 nM-100 nM. | | Incubation Time: | 72 h | | Result: | Showed good anti-proliferative activity with IC50s of 9.127 nM, and 17.10 nM for OCI-L Y10 and SU-DHL-6 cells, respectively. |
Apoptosis Analysis[1] | Cell Line: | SU-DHL-6 cells | | Concentration: | 0.5, 5, 50 μM | | Incubation Time: | 24, 48 h | | Result: | Induced cell apoptosis when concentration up to 50 μM and incubated for 48 h. |
Western Blot Analysis[2] | Cell Line: | TMD8 cells | | Concentration: | 300 nM | | Incubation Time: | 72 h | | Result: | Induced caspase-3 and PARP cleavage. |
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体内研究
(In Vivo) | Tirabrutinib hydrochloride (10 mg/kg; p.o.; single) is rapidly absorbed into plasma and brain, and reaches Cmax(blood Cmax=339.53 ng/mL; brain Cmax=28.9 ng/mL) 2 hours post administration[1].
Tirabrutinib hydrochloride (6, 20 mg/kg; p.o.; single daily for 3 weeks) shows inhibition of tumour growth in vivo[2].
| Animal Model: | Male SD rats (219.0–260.5g)[1]. | | Dosage: | 10 mg/kg | | Administration: | Oral administration; single. | | Result: | 1.19Pharmacokinetic Parameters of Tirabrutinib in male SD rats[1].
| Plasma, Cmax(ng/mL) | Brain, Cmax(ng/mL) | Penetration rate (%, Cmax, brain/Cmax, plasma) | | PO (10 mg/kg) | 339.53 | 28.9 | 8.5 |
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| Animal Model: | Immunodeficiency (SCID) mice (mouse xenograft model)[2]. | | Dosage: | 6, 20 mg/kg | | Administration: | Oral administration; single daily for 3 weeks. | | Result: | Inhibited tumour growth, and when dosage up to 20 mg/kg, a complete tumor suppression at day 14. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(203.69 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.0369 mL | 10.1845 mL | 20.3691 mL | | 5 mM | 0.4074 mL | 2.0369 mL | 4.0738 mL | | 10 mM | 0.2037 mL | 1.0185 mL | 2.0369 mL |
*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℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 2.5 mg/mL (5.09 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (5.09 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 2. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (5.09 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.09 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 1.79 mg/mL (3.65 mM); Clear solution
此方案可获得 ≥ 1.79 mg/mL (3.65 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 17.9 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 *以上所有助溶剂都可在本网站选购。
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