1. Protein Tyrosine Kinase/RTK
    Autophagy
  2. Btk
    Autophagy

CGI-1746 

Cat. No.: HY-11999 Purity: 96.62%
Data Sheet SDS Handling Instructions

CGI-1746 is a potent and highly selective inhibitor of the Btk with IC50 of 1.9 nM.

For research use only. We do not sell to patients.
CGI-1746 Chemical Structure

CGI-1746 Chemical Structure

CAS No. : 910232-84-7

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 89 In-stock
5 mg USD 70 In-stock
10 mg USD 110 In-stock
50 mg USD 190 In-stock
100 mg USD 290 In-stock
200 mg   Get quote  
500 mg   Get quote  

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

CGI-1746 is a potent and highly selective inhibitor of the Btk with IC50 of 1.9 nM.

IC50 & Target

IC50: 1.9 nM (Btk)

In Vitro

CGI1746 is specific for Btk, with appr 1,000-fold selectivity over Tec and Src family kinases. In an ATP-free competition binding assay, the dissociation constant for Btk is 1.5 nM. CGI1746 inhibits Btk activity in a new binding mode that stabilizes an inactive nonphosphorylated enzyme conformation. CGI1746 inhibits both auto- and transphosphorylation steps necessary for enzyme activation. CGI1746 completely inhibits anti-IgM-induced murine and human B cell proliferation, with IC50s of 134 nM and 42 nM, respectively, but has no effect on anti-CD3- and anti-CD28-induced T cell proliferation. CGI1746 potently inhibits the proliferation of CD27+IgG+ B cells isolated from the tonsils of four human donors with an average IC50 of 112 nM. In macrophages, CGI1746 abolishes FcγRIII-induced TNFα, IL-1β and IL-6 production. CGI1746 potently inhibits TNFα, IL-1β and, to a lesser extent, IL-6 (three- to eight-fold higher IC50) production in human monocytes stimulated with immobilized or soluble immune complexes[1]. CGI-1746 does not kill cells as well as the irreversible BTK inhibitors at the same drug concentration. CGI-1746 significantly reduces phosphorylation of both the BTK-A and BTK-C proteins, indicating the auto-phosphorylation of the BTK-C isoform is inhibited in a manner similar to BTK-A. CGI-1746 does not kill LNCaP or DU145 prostate cancer cells at the same concentrations as Ibrutinib or AVL-292, but it demonstrates similar inhibition of BTK phosphorylation at tyrosine 233 in the SH3 domain[2].

In Vivo

CGI1746 abrogates B cell-dependent arthritis. CGI1746 treatment (100 mg/kg, s.c, twice-daily dosing) results in significant inhibition (97%) of overall clinical arthritis scores. CGI1746 treatment substantially reduces TNFα, IL-1β and IL-6, as well as MCP1 and MIP-1α on both the mRNA and protein level in the passive anti-collagen II antibody-induced arthritis (CAIA) model. CGI1746 shows comparable efficacy to TNFα blockade and significantly reduces clinical scores, as well as joint inflammation, in mice or rats with established arthritis[1].

References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 1.7251 mL 8.6253 mL 17.2506 mL
5 mM 0.3450 mL 1.7251 mL 3.4501 mL
10 mM 0.1725 mL 0.8625 mL 1.7251 mL
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[2]

CGI-1746 is dissolved in DMSO.

5×103 DU145 cells or 104 LNCaP cells per well, grown on 96 well plates for 24h, are treated with 1 to 30 µM BTK inhibitors. Cells are fixed after 72h with 2.5% formaldehyde, and stained with Hoechst 33342. Control cells are treated with DMSO. Cell images are acquired using an IN Cell Analyzer 2200 high content imaging system, with a 20X objective. At least 9 fields are imaged per single well of each experiment. Cell numbers are determined and statistics performed using IN Cell Investigator 3.4 high content image analysis software. Each experiment is replicated 3 times, and data are presented as mean±SD. Results are considered significant if p < 0.05. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

579.69

Formula

C₃₄H₃₇N₅O₄

CAS No.

910232-84-7

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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CGI-1746
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HY-11999
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