Rilzabrutinib(Synonyms: PRN1008)

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Rilzabrutinib (Synonyms: PRN1008) 纯度: 98.22%

Rilzabrutinib (PRN1008) 是布鲁顿氏酪氨酸激酶 (BTK) 可逆的、选择性的、有口服活性的共价抑制剂,其 IC50 值为 1.3 nM。

Rilzabrutinib(Synonyms: PRN1008)

Rilzabrutinib Chemical Structure

CAS No. : 1575596-29-0

规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ¥4248 In-stock
5 mg ¥2900 In-stock
10 mg ¥4600 In-stock
25 mg ¥9200 In-stock
50 mg 询价
100 mg 询价

* Please select Quantity before adding items.

Rilzabrutinib 相关产品

相关化合物库:

  • Covalent Screening Library Plus
  • Drug Repurposing Compound Library Plus
  • Clinical Compound Library Plus
  • Bioactive Compound Library Plus
  • Kinase Inhibitor Library
  • Protein Tyrosine Kinase Compound Library
  • Anti-Cancer Compound Library
  • Clinical Compound Library
  • Drug Repurposing Compound Library
  • Covalent Screening Library
  • Orally Active Compound Library
  • Anti-Blood Cancer Compound Library
  • Rare Diseases Drug Library

生物活性

Rilzabrutinib (PRN1008) is a reversible covalent, selective and oral active inhibitor of Bruton’s Tyrosine Kinase (BTK), with an IC50 of 1.3 nM.

IC50 & Target[1][2]

BTK

1.3 nM (IC50)

BMX

1.0 nM (IC50)

ITK

440 nM (IC50)

TEC

0.8 nM (IC50)

RLK

1.2 nM (IC50)

BLK

6.3 nM (IC50)

EGFR

520 nM (IC50)

ERBB2

3900 nM (IC50)

ERBB4

11.3 nM (IC50)

体外研究
(In Vitro)

Rilzabrutinib is a reversible covalent inhibitor of Bruton’s Tyrosine Kinase (BTK), with an IC50 of 1.3±0.5 nM. Rilzabrutinib is also found to be highly selectively when tested in a panel of 251 other kinases. Cysteine targeting of BTK by Rilzabrutinib results in a slow off-rate demonstrated by retention of 79±2% of binding to BTK in PBMC 18 hours after washing away the compound in vitro. The covalent cysteine binding is completely reversible after denaturation of the target. Anti-IgM induces human B cell proliferation (10% serum) and B cell CD69 expression are inhibited by Rilzabrutinib with IC50 of 5±2.4 nM and 123±38 nM, respectively[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究
(In Vivo)

In vivo Rilzabrutinib demonstrates enduring pharmacodynamic effects after the compound has cleared from circulation, consistent with extended target residence time. Rilzabrutinib also reverses and completely suppresses collagen-induced arthritis in rats in a dose dependent manner which allows correlation of target occupancy and disease modification[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

分子量

665.76

Formula

C36H40FN9O3

CAS 号

1575596-29-0

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : ≥ 130 mg/mL (195.27 mM)

* “≥” means soluble, but saturation unknown.

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 1.5020 mL 7.5102 mL 15.0204 mL
5 mM 0.3004 mL 1.5020 mL 3.0041 mL
10 mM 0.1502 mL 0.7510 mL 1.5020 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。-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    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 2.08 mg/mL (3.12 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (3.12 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 20.8 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

  • 2.

    请依序添加每种溶剂: 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 2.08 mg/mL (3.12 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (3.12 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 20.8 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
  • 3.

    请依序添加每种溶剂: 10% DMSO    90% corn oil

    Solubility: ≥ 2.08 mg/mL (3.12 mM); Clear solution

    此方案可获得 ≥ 2.08 mg/mL (3.12 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 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
  • [1]. Smith PF, et al. A phase I trial of PRN1008, a novel reversible covalent inhibitor of Bruton’s tyrosine kinase, in healthy volunteers. Br J Clin Pharmacol. 2017 Nov;83(11):2367-2376.

    [2]. Hill RJ, Bradshaw JM, Bisconte A, Tam D, Owens TD, Brameld KA, Smith PF, Funk JO, Goldstein DM, Nunn PA. Preclinical Characterization of PRN1008, a Novel Reversible Covalent Inhibitor of BTK that Shows Efficacy in a RAT Model of Collagen-Induced Arthritis. Annals of the Rheumatic Diseases 2015; 74(Suppl 2): 216.

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