Disease relevance of

• The combination of immunosuppression, previously described, along with anti-inflammatory properties makes SR 31747 a novel attractive molecule for therapeutic applications such as autoimmune diseases in which both immune and inflammatory disorders are involved [1].
• In vivo, in mice, treatment with SR 31747 prevented both graft-versus-host disease and delayed-type hypersensitivity granuloma formation, while antibody response to sheep red blood cells was not affected [2].

High impact information on

• Sterol isomerase activity is also inhibited by SR 31747 in in vitro assays [3].
• SR 31747 is a novel immunosuppressant agent that arrests cell proliferation in the yeast Saccharomyces cerevisiae, SR 31747-treated cells accumulate the same aberrant sterols as those found in a mutant impaired in delta 8- delta 7-sterol isomerase [3].
• The ERG2 gene product has been identified recently as the molecular target of SR 31747A that mediates antiproliferative effects of the drug in yeast [4].
• SR 31747A, defined as a sigma ligand, is a novel immunosuppressive agent that blocks proliferation of human and mouse lymphocytes [4].
• Using a radiolabeled chemical probe, we here purified a target of SR 31747A and called it SR 31747A-binding protein (SR-BP) [4].

Biological context of

• Allosteric modulation of peripheral sigma binding sites by a new selective ligand: SR 31747 [5].
• In vitro, our study shows that SR 31747 exerts a concentration- and time-dependent inhibition of proliferative response to mitogens on mouse and human lymphocytes without affecting cell viability [2].
• We showed that the SR 31747 effect, which was observed on purified T lymphocytes, affects a late event in the activation process which occurs after the G1 during the S phase of the cell cycle [2].

Anatomical context of

• Taken together, these findings strongly suggest that SR-BP represents the molecular target for SR 31747A in mammalian tissues, which could be critical for T cell proliferation [4].
• Purification and characterization of the human SR 31747A-binding protein. A nuclear membrane protein related to yeast sterol isomerase [4].
• The enhancement of IL-10 production by SR 31747A treatment was also apparent in nude and severe-combined immunodeficient mice treated with LPS, clearly indicating that T and B cells were not involved [6].
• Nanomolar concentrations of SR 31747 selectively inhibited in a non-competitive manner the binding of the prototypic sigma ligands [3H](+)-pentazocine, [3H](+)-3PPP and [3H]DTG on rat spleen membranes [5].
• Here the effect of SR 31747 on the proinflammatory cytokine production by endotoxin-activated macrophages is examined [1].

Associations of with other chemical compounds

• This conclusion was supported by in vivo experiments that showed that 1) ablation of corticosteroids by use of mifepristone or adrenalectomy suppressed the effect of SR 31747 and 2) administration of SR 31747 induced an enhancement of the corticosterone level [1].
• This antibody was produced from spleen lymphocytes of a mouse immunized with SR 31747A coupled to bovine serum albumin via a peptide bond using SR 120684A, a succinamic acid derivative of SR 31747A [7].

Gene context of

• Cytokine messenger RNA analyses on spleen cells revealed that SR 31747 blocked IFN-gamma and GM-CSF but not IL-4 transcription [8].
• Because SR 31747 blocked the GvHR-induced expression of both interleukin-2 and transferrin receptors on T-lymphocytes, it is very likely that this molecule prevented the disease through an inhibition of T-lymphocyte activation [8].
• Enhancement of endotoxin-induced interleukin-10 production by SR 31747A, a sigma ligand [6].
• Whereas SR 31747 suppression was not observed in vitro on lipopolysaccharide-induced IL-6 by macrophages, sera from SR 31747-treated animals displayed a strong inhibitory activity [1].
• In vivo, SR 31747 dramatically blocked lipopolysaccharide-induced production of interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha in a dose-dependent manner (ED50, 2 mg/kg) [1].

Analytical, diagnostic and therapeutic context of

• Development of a radioimmunoassay for SR 31747A, a new sigma ligand, in human plasma [7].

References