ONO-4059
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
ONO-4059对Btk激酶活性的IC50值为2.2 nM.
布鲁顿氏酪氨酸激酶(Btk)在B细胞受体(BCR)途径中起关键调控作用,异常的BCR信号与恶性B细胞存活相关.以往研究表明,靶向作用于Btk能有效地治疗B细胞恶性肿瘤.ONO-4059是一种高度有效的口服Btk选择性抑制剂.
体外:ONO-4059呈浓度依赖性地抑制TMD-8细胞生长以及Btk磷酸化.此外,Btk磷酸化的减少引起Erk磷酸化下调.ONO-4059与Doxorubicin\Etoposide\Vincristine以及Dexamethasone联合用药增加凋亡率,相应的凋亡率为25%\20%\17%和29%[1].
体内:在100 ~ 200 mm3肿瘤组中,于治疗的最后一天,肿瘤生长抑制率分别是23%(QD组)\72.9%(BD组)以及100%(药物食物混合组).在400 ~ 450 mm3肿瘤组中,QD组没有出现生长抑制,而BD组与药物食物混合组的肿瘤生长抑制率分别为27.5%和100%.相对于其它治疗组,药物食物混合组中的动物具有较高的PK浓度以及磷酸化Btk抑制水平[2].
临床试验:ONO-4059是一种高度有效的口服Btk选择性抑制剂,有望用于安全地和有效地治疗复发/难治性B细胞淋巴瘤[3].
参考文献：
[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.
| Physical Appearance | A crystalline solid |
| Storage | Store at -20°C |
| M.Wt | 456.5 |
| Cas No. | 1351635-67-0 |
| Formula | C25H24N6O3 |
| Solubility | Soluble in DMSO |
| Chemical Name | (S)-9-(1-acryloylpiperidin-3-yl)-6-amino-7-(4-phenoxyphenyl)-7H-purin-8(9H)-one |
| SDF | Download SDF |
| 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 |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
化学结构
