Bruton’s tyrosine kinase (BTK) is a non-receptor tyrosine kinase that plays a critical role in development, differentiation and proliferation of B-lineage cells. CGI-1746 is an ATP-competitive small molecule inhibitor of BTK with IC50 value of 1.9 nM. In vitro, CGI-1746 potently inhibited all three anti-IgM-induced phosphorylation events in both human and murine B cells with an average IC50 value of 2.9 nM, and completely inhibited the proliferation of CD27+IgG+ B cells, anti-IgM-induced murine and human B cell, with IC50 values of 112 nM, 134 nM and 42 nM, respectively. However, CGI1746 had no effect on anti-CD3 and anti-CD28 induced T cell proliferation[3]. CGI1746 could also inhibit the growth of human myeloma cell line APR1 and OCI-MY5 with IC50 value of 10 μM[4]. CGI1746 decreases cytokine levels within joints and ameliorates disease in myeloid- and FcgR-dependent autoantibody-induced arthritis. In vivo, administration of 100 mg/kg twice-daily with CGI-1746 for 4 weeks significantly inhibited overall clinical arthritis scores, and reduced anti-collagen II titers[3]. CCGI-1746 suppressed TNFα, IL-1β, IL-6, MCP1 and MIP-1α production in the passive anti-collagen II antibody induced arthritis (CAIA) model. Treatment with CGI-1746 at the dose of 200 mg/kg twice a week for 30 days can inhibit the growth of human OCI-MY5 xenografts in NSG mice[4].
CGI-1746 细胞实验
Cell Line
Concentration
Treated Time
Description
References
human foreskin fibroblasts (HFFs)
5 μM
7 days
Evaluate the effect of CGI-1746 on parasite plaque formation, showing a reduction in plaque area by approximately 91%
Front Cell Infect Microbiol. 2023 Apr 3;13:1145824
OPM2 cells
0.2 μM to 50 μM
48 h
Test the inhibitory effect of CGI1746 on HMCLs, showing IC50 of approximately 10 μM for ARP1 and OPM2 cells
Cancer Res. 2015 Feb 1;75(3):594-604
ARP1 cells
0.2 μM to 50 μM
48 h
Test the inhibitory effect of CGI1746 on HMCLs, showing IC50 of approximately 10 μM for ARP1 and OPM2 cells
Cancer Res. 2015 Feb 1;75(3):594-604
MDA-MB-231 cells
20 μM
4 h
RNA sequencing analysis of the effects of CGI-1746 on cells revealed that CGI-1746 alone significantly upregulated HSP70 gene expression
iScience. 2024 Sep 24;27(11):110961
INA-6 cells
10 μM
48 h
Evaluate the synergistic cytotoxic effect of CGI-1746 with the proteasome inhibitor LU-102, showing that CGI-1746 combined with LU-102 significantly reduced cell viability
iScience. 2024 Sep 24;27(11):110961
CGI-1746 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/KaLwRij mice
5TGM1 myeloma model
Subcutaneous injection
100 mg/kg
Three times per week, starting 7 days post-injection
Test the therapeutic effect of CGI1746 on the 5TGM1 myeloma model, showing significantly prolonged median survival in the treatment group (57 days vs 39 days)
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