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Biotech / Medical : Transkaryotic(tktx)

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To: Scott who wrote (5)	6/6/1998 10:26:00 PM
From: Henry Niman	Read Replies (1) of 122

I expect to see a major paper in Science in the next few weeks on a Neupogen mimic discovered by Ligand (LGND). I have created a page with links to additional information at home.att.net. Here is an abstract for an upccoming presentation: Discovery Of A Small Molecule G-Csf Mimic Jonathan I. Rosen, Ph.D., Senior Director, Transcription Research and New Leads Discovery, Ligand Pharmaceuticals, Inc. The JAK/STAT signal transduction pathway utilized by many cytokines can be exploited to develop high throughput screens for small molecule cytokine modulators. We applied this approach to the discovery of G-CSF mimics and have identified a non-peptidyl small molecule capable of activating granulocyte-colony stimulating factor (G-CSF) signal transduction pathways. This compound induces both the biochemical and cellular phenotypic responses characteristic of G-CSF. Remarkably, this compound is active in vivo with an efficacy similar to recombinant G-CSF. The identification of this compound provides proof of principle for drug discovery using JAK/STAT-based assays, and shows for the first time that a small non-peptidyl molecule can trigger the selective activation of a protein hormone receptor.

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