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. "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.
Chemical compound shows promise as treatment for autoimmune
Re: Chemical compound shows promise as treatment for autoimm
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.
Re: Chemical compound shows promise as treatment for autoimm
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.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.
Re: Chemical compound shows promise as treatment for autoimm
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.
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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