CGI-1746 |
| Catalog No.GC13365 |
A potent, selective BTK inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 910232-84-7
Sample solution is provided at 25 µL, 10mM.
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CGI-1746 is a selective and potent inhibitor of Bruton's tyrosine kinase (BTK) with IC50 value of 1.9 nM [1][2].
Bruton's tyrosine kinase (BTK) is a member of the Tec tyrosine kinase family and plays an important role in differentiation, proliferation and development of B cells. It is an attractive target for the treatment of immunological disorders such as B-cell malignancies, rheumatoid arthritis (RA), multiple sclerosis (MS) and lupus [3].
CGI-1746 potently inhibits both auto- and transphosphorylation of BTK. It binds to un-phosphorylated BTK and stabilizes it in an inactive enzyme state. In cellular assays, CGI-1746 blocks BCR-mediated B-cell proliferation and suppresses the production of IL-6, IL-1βand TNF in macrophages [1].
In experimental mouse models, CGI-1746 shows a robust anti-arthritic activity [1]. In B10.RIII mice model, CGI1746 resulted in a significant inhibition (97%) of clinical arthritis scores, which were better than dexamethasone treatment (56% inhibition) [2].
References:
[1]. Akinleye A, Chen Y, Mukhi N, et al. Ibrutinib and novel BTK inhibitors in clinical development. J Hematol Oncol, 2013, 6: 59.
[2]. Di Paolo JA, Huang T, Balazs M, et al. Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Nat Chem Biol, 2011, 7(1): 41-50.
[3]. Young WB, Barbosa J, Blomgren P, et al. Potent and selective Bruton's tyrosine kinase inhibitors: discovery of GDC-0834. Bioorg Med Chem Lett, 2015, 25(6): 1333-1337.
| Cell experiment [1]: | |
|
Cell lines |
Human B cells |
|
Preparation method |
The solubility of this compound in DMSO is > 29 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
|
Reacting condition |
0.003 ~ 10 μM |
|
Applications |
In human B cells, CGI-1746 potently inhibited anti-IgM-induced phosphorylation of Btk Tyr223, Btk Tyr551 and PLCγ2 Tyr1217, with an average IC50 value of 2.9 nM. In addition, CGI-1746 lowered the basal phosphorylation levels of Btk Tyr551 and Tyr223, but not the basal phosphorylation of PLCγ2 Tyr1217. |
| Animal experiment [1]: | |
|
Animal models |
Collagen-induced arthritis (CIA) mouse model |
|
Dosage form |
100 mg/kg; s.c.; b.i.d., from day 12 to day 26 |
|
Applications |
CGI-1746 significantly inhibited overall clinical arthritis scores (97% inhibition). Moreover, CGI-1746 substantially reduced anti-collagen II (CII) titers. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1]. Di Paolo JA, Huang T, Balazs M, et al. Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. Nat Chem Biol, 2011, 7(1): 41-50. | |
| Cas No. | 910232-84-7 | SDF | |
| Chemical Name | 4-tert-butyl-N-[2-methyl-3-[4-methyl-6-[4-(morpholine-4-carbonyl)anilino]-5-oxopyrazin-2-yl]phenyl]benzamide | ||
| Canonical SMILES | CC1=C(C=CC=C1NC(=O)C2=CC=C(C=C2)C(C)(C)C)C3=CN(C(=O)C(=N3)NC4=CC=C(C=C4)C(=O)N5CCOCC5)C | ||
| Formula | C34H37N5O4 | M.Wt | 579.71 |
| Solubility | ≥ 29 mg/mL in DMSO, ≥ 6.72 mg/mL in EtOH with ultrasonic and warming | 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. |
||
| 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 | 1.725 mL | 8.625 mL | 17.25 mL |
| 5 mM | 0.345 mL | 1.725 mL | 3.45 mL |
| 10 mM | 0.1725 mL | 0.8625 mL | 1.725 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: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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