ONO-4059
(Synonyms: GS-4059 analog) 目录号 : GC13219
A derivative of ONO-4059
Cas No.:1351635-67-0
Sample solution is provided at 25 µL, 10mM.
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Description:
IC50: 2.2 nM for Btk kinase activity
Bruton’s tyrosine kinase (Btk) is a key regulator of the B-cell receptor (BCR) pathway and abberant BCR signaling has been implicated in the survival of malignant B-cells. Previous studies indicate that targeting Btk is effective in the treatment of B-cell malignancies. ONO-4059 is a highly potent and selective oral Btk inhibitor.
In vitro: ONO-4059 inhibited the TMD-8 cell growth and Btk phosphorylation in a concentration-dependent manner. Furthermore, the decrease in Btk phosphorylation subsequently down-regulated Erk phosphorylation. After the combination of ONO-4059 with doxorubicin, etoposide, vincristine and dexamethasone, increased apoptosis ratio was observed, 25, 20, 17 and 29%, respectively [1].
In vivo: For the 100-200 mm3 tumour groups, tumour growth inhibition at the final treatment day was 23% in QD, 72.9% in BD and 100% in dose mixed in food, groups respectively. For the 400-450 mm3 tumour groups, no growth inhibition was observed in the QD group and, growth inhibitions of 27.5% in BD and 100% in dose mixed in food were observed. The PK concentration and phosphorylated Btk inhibition levels of those animals whose dose was mixed in with food were higher than that of other treatment groups [2].
Clinical trial: ONO-4059 is a highly potent and selective oral Btk inhibitor that shows a favourable safety profile along with promising efficacy in this difficult-to-treat patient population with relapsed/refractory B-Cell lymphoma [3].
Reference:
[1] Tomoko Yasuhiro, Toshio Yoshizawa, Joseph TP Birkett, and Kazuhito Kawabata. ONO-4059, A Novel Bruton’s Tyrosine Kinase (Btk) Inhibitor: Synergistic Activity In Combination With Chemotherapy In a ABC-DLBCL Cell Line. 2013; Blood: 122 (21): 5151 - 5151
[2] Toshio Yoshizawa, Tomoko Yasuhiro, Hideyuki Honda, and Kazuhito Kawabata. ONO-4059—a Potent and Selective Reversible Bruton’s Tyrosine Kinase (Btk) Inhibitor: Single Agent, Twice Daily (BD) Dosing and Dosing with Food Results in Sustained, High Trough Levels of ONO-4059, Translating into 100% Tumour Remission in a TMD-8 Xenograft Model. 2014; Blood: 124 (21) 4502 - 4502
[3] Simon Rule, Nimish Shah, Gilles Andre Salles et al. A Phase I Study Of The Oral Btk Inhibitor ONO-4059 In Patients With Relapsed/Refractory B-Cell Lymphoma. Blood. 2013 122 (21): 4397 – 4397.
| Cas No. | 1351635-67-0 | SDF | |
| 别名 | GS-4059 analog | ||
| 化学名 | (S)-9-(1-acryloylpiperidin-3-yl)-6-amino-7-(4-phenoxyphenyl)-7H-purin-8(9H)-one | ||
| Canonical SMILES | NC1=C(N(C(N2[C@@H]3CN(C(C=C)=O)CCC3)=O)C(C=C4)=CC=C4OC5=CC=CC=C5)C2=NC=N1 | ||
| 分子式 | C25H24N6O3 | 分子量 | 456.5 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,DMSO:PBS (pH 7.2) (1:2): 0.3 mg/ml,Ethanol: 1 mg/ml | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1906 mL | 10.9529 mL | 21.9058 mL |
| 5 mM | 0.4381 mL | 2.1906 mL | 4.3812 mL |
| 10 mM | 0.2191 mL | 1.0953 mL | 2.1906 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet