ONO-4059 (Synonyms: GS-4059 analog) |
| カタログ番号GC13219 |
ONO-4059 は ONO-4059 の類似体であり、ONO-4059 は非常に強力で選択的な Btk 阻害剤です。
Products are for research use only. Not for human use. We do not sell to patients.
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 | |
| 同義語 | GS-4059 analog | ||
| Chemical Name | (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 | ||
| Formula | C25H24N6O3 | M.Wt | 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 | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 19 reference(s) in Google Scholar.)
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