Chemical compound shows promise as treatment for autoimmune

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Chemical compound shows promise as treatment for autoimmune

Postby NHE » Wed Mar 26, 2014 4:11 am

http://www.bizjournals.com/portland/blo ... or-ms.html

Researchers at Oregon State University have identified a chemical compound that could be used to more safely treat patients with autoimmune diseases. After testing thousands of compounds, scientists uncovered 10-CI-BBQ, which binds to a T-cell protein, and together they pass into the nucleus to shut down the immune response by changing the cells into regulatory T cells, according the study published in PLoS ONE. "[I]f this chemical works in clinical studies, it could result in a safer alternative to conventional drugs," Nancy Kerkvliet, lead researcher, said in a statement.
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Re: Chemical compound shows promise as treatment for autoimm

Postby Kronk » Wed Mar 26, 2014 8:40 am

Very exciting... they are getting closer to treating the root cause vs. the side effects. Dont suppress the immune system change how it targets or mis-fires.
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Re: Chemical compound shows promise as treatment for autoimm

Postby NHE » Wed Mar 26, 2014 3:33 pm

Kronk wrote:Very exciting... they are getting closer to treating the root cause vs. the side effects. Dont suppress the immune system change how it targets or mis-fires.


That's what we thought Tovaxin/Tcelna would do. Maybe this approach will be more effective. We'll have to wait and see. It's still quite early.
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Re: Chemical compound shows promise as treatment for autoimm

Postby NHE » Wed Mar 26, 2014 10:58 pm

The full paper is available.

Benzimidazoisoquinolines: A New Class of Rapidly Metabolized Aryl Hydrocarbon Receptor (AhR) Ligands that Induce AhR-Dependent Tregs and Prevent Murine Graft-Versus-Host Disease.
PLoS One. 2014 Feb 19;9(2):e88726.

    The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that plays multiple roles in regulation of immune and inflammatory responses. The ability of certain AhR ligands to induce regulatory T cells (Tregs) has generated interest in developing AhR ligands for therapeutic treatment of immune-mediated diseases. To this end, we designed a screen for novel Treg-inducing compounds based on our understanding of the mechanisms of Treg induction by the well-characterized immunosuppressive AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We screened a ChemBridge small molecule library and identified 10-chloro-7H-benzimidazo[2,1-a]benzo[de]Iso-quinolin-7-one (10-Cl-BBQ) as a potent AhR ligand that was rapidly metabolized and not cytotoxic to proliferating T cells. Like TCDD,10-Cl-BBQ altered donor CD4(+) T cell differentiation during the early stages of a graft versus host (GVH) response resulting in expression of high levels of CD25, CTLA-4 and ICOS, as well as several genes associated with Treg function. The Treg phenotype required AhR expression in the donor CD4(+) T cells. Foxp3 was not expressed in the AhR-induced Tregs implicating AhR as an independent transcription factor for Treg induction. Structure-activity studies showed that unsubstituted BBQ as well as 4, 11-dichloro-BBQ were capable of inducing AhR-Tregs. Other substitutions reduced activation of AhR. Daily treatment with 10-Cl-BBQ during the GVH response prevented development of GVH disease in an AhR-dependent manner with no overt toxicity. Together, our data provide strong support for development of select BBQs that activate the AhR to induce Tregs for treatment of immune-mediated diseases.
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