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BD750, a Benzothiazole Derivative, Inhibits T Cell Proliferation by Affecting the JAK3/STAT5 Signalling Pathway

BD750, a Benzothiazole Derivative, Inhibits T Cell Proliferation by Affecting the JAK3/STAT5 Signalling Pathway

Y Liu, T Yang, H Li, M-H Li, J Liu, Y-T Wang, S-X Yang, J Zheng, X-Y Luo, Y Lai, P Yang, L-M Li, Q Zou

Br J Pharmacol. 2013 Feb;168(3):632-43.

PMID: 22906008

Abstract:

Background and purpose:
A series of benzothiazole derivatives were screened for immunosuppressive activity; of these compounds BD750 was found to be the most effective immunosuppressant. The purpose of the current study was to determine the immunosuppressive activity of BD750 on T cell proliferation and its potential mode of action.
Experimental approach:
T cell proliferation, CD25 and CD69 expression and cell cycle distribution were measured in vitro by flow cytometry. Cell viability was determined by CCK-8 assay. Cytokine levels were measured by elisa. The activation of signal-regulated molecules was assessed by Western blot analysis. The effects of BD750 were evaluated in vivo in a mouse model of delayed-type hypersensitivity.
Key results:
BD750 significantly inhibited mouse and human T cell proliferation, stimulated either by anti-CD3/anti-CD28 monoclonal antibodies or by an alloantigen, in a dose-dependent manner in vitro. No obvious cytotoxic effects of BD750 were observed in our experimental conditions. Furthermore, BD750 did not inhibit CD25 and CD69 expression or IL-2 and IL-4 secretion, but induced cell cycle arrest at the G(0) /G(1) phase in activated T cells. In IL-2-stimulated CTLL-2 cells and primary activated T cells, BD750 inhibited cell proliferation and STAT5 phosphorylation, but not Akt or p70S6K phosphorylation. BD750 also reduced the T cell-mediated delayed-type hypersensitivity response in mice in a dose-dependent manner.
Conclusion and implications:
These data indicate that BD750 inhibits IL-2-induced JAK3/STAT5-dependent T cell proliferation. BD750 has the potential to be used as a lead compound for the design and development of new immunosuppressants for preventing graft rejection and treating autoimmune diseases.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP892686598	BD750		892686-59-8	Price

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