Bernie. LGND will be presenting next week at the Endocrine Society meeting in New Orleans. Are you going? Here's one of the abstracts:
S04-1 A PHARMACOLOGICAL DISSECTION OF RXR SIGNALING PATHWAYS WITH REXINOIDS RA Heyman1, 1,
Ligand Pharmaceuticals, San Diego, CA,
Receptor X receptor (RXR) plays a central role in the regulation of many intracellular receptor signaling pathways. To examine
signaling pathways mediated by RXR and its partners we have designed and characterized a series of synthetic ligands that
bind RXR and modulate its transcriptional properties. These RXR ligands, referred to as rexinoids, are dimer selective in that
they can function as agonists and/or antagonists depending upon the context of the homodimer or heterodimer partner. These
rexinoids have been used as pharmacological tools in a multitude of molecular, cellular and animal models. In animal models of
non-insulin dependent diabetes mellitus (NIDDM) and obesity, RXR agonists function as insulin sensitizers significantly
decreasing hyperglycemia and hyperinsulinemia. When RXR agonists are used during early stages of insulin resistance they
block the progression of NIDDM. These data suggest that activation of the RXR:PPARg heterodimer with rexinoids may
provide a new therapeutic opportunity for the treatment of insulin resistance. The previous use of retinoids in cancer therapy
and chemoprevention prompted us to investigate the activity of RXR ligands in this therapeutic setting. In a carcinogen
induced breast cancer model, RXR agonists are as effective as tamoxifen in the prevention of mammary carcinomas. In animals
that have an established breast tumor, RXR agonists cause complete regression of the tumor. These two distinct models
suggest that the ability of RXR to dimerize with distinct receptors allows rexinoids to alter transcriptional signaling of distinct
endocrine signaling pathways and offers new opportunities for the effective treatment of certain disease states.
Presentation Date, Time, Room: 24-Jun-98, 9:30A, CC-38 |
