Tirabrutinib hydrochloride ONO-4059 hydrochloride; GS-4059 hydrochloride|cas:1439901-97-9|西域试剂

Tirabrutinib hydrochloride ONO-4059 hydrochloride; GS-4059 hydrochloride,99.43%

产品编号：Bellancom-15771A| CAS NO：1439901-97-9| 分子式：C₂₅H₂₃ClN₆O₃| 分子量：490.94

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货号	价格	库存与货期
Bellancom-15771A	￥600.00	杭州北京（现货）
Bellancom-15771A	￥1000.00	杭州北京（现货）
Bellancom-15771A	￥2000.00	杭州北京（现货）
Bellancom-15771A	￥3500.00	杭州北京（现货）
Bellancom-15771A	￥6000.00	杭州北京（现货）

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Tirabrutinib hydrochloride ONO-4059 hydrochloride; GS-4059 hydrochloride

产品介绍

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 active Bruton’s Tyrosine Kinase (BTK) inhibitor (can cross the blood-brain barrier (BBB)), with an IC₅₀ of 6.8 nM. Tirabrutinib hydrochloride irreversibly and covalently binds to BTK and inhibits aberrant B cell receptor signaling. Tirabrutinib hydrochloride can be used in studies of autoimmune diseases and hematological malignancies^[4].

体外研究

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.
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).
Tirabrutinib hydrochloride (300 nM, 72 h) induces caspase-3 and PARP cleavage in TMD8 cells.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay

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

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

Cell Line:	TMD8 cells
Concentration:	300 nM
Incubation Time:	72 h
Result:	Induced caspase-3 and PARP cleavage.

体内研究
(In Vivo)

Tirabrutinib hydrochloride (10 mg/kg; p.o.; single) is rapidly absorbed into plasma and brain, and reaches C_max (blood C_max =339.53 ng/mL; brain C_max =28.9 ng/mL) 2 hours post administration.
Tirabrutinib hydrochloride (6, 20 mg/kg; p.o.; single daily for 3 weeks) shows inhibition of tumour growth in vivo.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Male SD rats (219.0–260.5g).

Dosage:

10 mg/kg

Administration:

Oral administration; single.

Result:

1.19 Pharmacokinetic Parameters of Tirabrutinib in male SD rats.

	Plasma, C_max (ng/mL)	Brain, C_max (ng/mL)	Penetration rate (%, C_{max, brain}/C_{max, plasma})
PO (10 mg/kg)	339.53	28.9	8.5

Animal Model:	Immunodeficiency (SCID) mice (mouse xenograft model).
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.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Male SD rats (219.0–260.5g).

Dosage:

10 mg/kg

Administration:

Oral administration; single.

Result:

1.19 Pharmacokinetic Parameters of Tirabrutinib in male SD rats.

	Plasma, C_max (ng/mL)	Brain, C_max (ng/mL)	Penetration rate (%, C_{max, brain}/C_{max, plasma})
PO (10 mg/kg)	339.53	28.9	8.5

Animal Model:	Immunodeficiency (SCID) mice (mouse xenograft model).
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.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Male SD rats (219.0–260.5g).

Dosage:

10 mg/kg

Administration:

Oral administration; single.

Result:

1.19 Pharmacokinetic Parameters of Tirabrutinib in male SD rats.

	Plasma, C_max (ng/mL)	Brain, C_max (ng/mL)	Penetration rate (%, C_{max, brain}/C_{max, plasma})
PO (10 mg/kg)	339.53	28.9	8.5

Animal Model:	Immunodeficiency (SCID) mice (mouse xenograft model).
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.

性状

Solid

溶解性数据

In Vitro:

DMSO : 100 mg/mL (203.69 mM; Need ultrasonic)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

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°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-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。

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-CD in 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 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。
将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
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。
将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液