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CGI-1746

Catalog No.
A3302
Btk inhibitor
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$120.00
In stock
10mg
$155.00
In stock
50mg
$540.00
In stock
100mg
$940.00
In stock

Tel: +1-832-696-8203

Email: [email protected]

Worldwide Distributors

Background

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.

Product Citation

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt579.71
Cas No.910232-84-7
FormulaC34H37N5O4
SynonymsCGI1746;CGI 1746
Solubility≥29 mg/mL in DMSO, ≥6.72 mg/mL in EtOH with ultrasonic and warming, insoluble in H2O
Chemical Name4-tert-butyl-N-[2-methyl-3-[4-methyl-6-[4-(morpholine-4-carbonyl)anilino]-5-oxopyrazin-2-yl]phenyl]benzamide
SDFDownload SDF
Canonical SMILESCC1=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
Shipping ConditionEvaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Protocol

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.

Biological Activity

Description CGI1746 is a potent and highly selective small-molecule inhibitor of the Btk with IC50 value of 1.9 nM.
Targets Btk          
IC50 1.9 nM          

Quality Control

Quality Control & MSDS

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Chemical structure

CGI-1746

Related Biological Data

CGI-1746