Ligand (LGND) Breakout! Message Board

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Biotech / Medical : Ligand (LGND) Breakout!

LGND 197.37

-0.3%

3:59 PM EST

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To: Len who wrote (26770)	12/7/1998 10:55:00 AM
From: Henry Niman	Read Replies (1) of 32384

Rezulin is a first generation TZD (a small molecule that activates the hormone receptor PPARgamma). LGND has a TZD program designed to identify 2nd generation small molecules that will activate PPARgamma without causing side effects like liver damage). In addition to its TZD program, LGND has an active retinoid/rexinoid program. These are small molecules that activate another set of hormone receptors (RARs and RXRs). Those that are specific for RXRs are called rexinoids (those specific for RARs are called retinoids). One of LGND's rexinoids, Targretin, is in advanced clinical trials for treating cancer (CTCL is the most advanced) as well as diabetes (Phase II in Europe). LGND has two other rexinoids, LGD1268 and LGD1324 which are just about ready to enter the clinic) TZDs that activate PPARgamma turn on genes that increase insulin sensitivity. However, the active molecule is actually a heterodimer composed of an activated PPARgamma paired with an activated RXRalpha. Since LGND's rexinoids activate RXRalpha, they synergize with TZDs (such as WLA's Rezulin or SBH's Avandia - the NDA for Avandia was filed last month). In animal models of diabetes, LGND's rexinoids (Targretin and LGD1268), synergize with TZDs (Rezulin and Avandia). Details are linked to the Ligand Diabetes page (TZD/Rexinoid table) at biocognizance.com .

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