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Biotech / Medical : Ligand (LGND) Breakout! -- Ignore unavailable to you. Want to Upgrade?

To: RevMikeB who wrote (23000)	7/9/1998 8:51:00 PM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Here's the Science abstract: A Small, Nonpeptidyl Mimic of Granulocyte-Colony- Stimulating Factor Shin-Shay Tian, * Peter Lamb, * Andrew G. King, Stephen G. Miller, Linda Kessler, Juan I. Luengo, Laurie Averill, Randall K. Johnson, John G. Gleason, Louis M. Pelus, Susan B. Dillon, Jonathan Rosen A nonpeptidyl small molecule SB 247464, capable of activating granulocyte-colony-stimulating factor (G-CSF) signal transduction pathways, was identified in a high-throughput assay in cultured cells. Like G-CSF, SB 247464 induced tyrosine phosphorylation of multiple signaling proteins and stimulated primary murine bone marrow cells to form granulocytic colonies in vitro. It also elevated peripheral blood neutrophil counts in mice. The extracellular domain of the murine G-CSF receptor was required for the activity of SB 247464, suggesting that the compound acts by oligomerizing receptor chains. The results indicate that a small molecule can activate a receptor that normally binds a relatively large protein ligand. S.-S. Tian, P. Lamb, L. Kessler, J. Rosen, Department of Transcription Research, Ligand Pharmaceuticals, San Diego, CA 92121, USA. A. G. King, L. Averill, L. M. Pelus, S. B. Dillon, Department of Molecular Virology and Host Defence-US, SmithKline Beecham Pharmaceuticals, Collegeville, PA 19426, USA. S. G. Miller, Department of New Leads Discovery, Ligand Pharmaceuticals, San Diego, CA 92121, USA. J. I. Luengo and J. G. Gleason, Department of Medicinal Chemistry-US, SmithKline Beecham Pharmaceuticals, Collegeville, PA 19426, USA. R. K. Johnson, Department of Oncology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA. * These authors contributed equally to this work. To whom correspondence should be addressed. E-mail: plamb@ligand.com Related articles in Science: DRUG DEVELOPMENT: Small Molecule Fills Hormone's Shoes. Marcia Barinaga Science 1998 281: 149-150. (in News of the Week) [Summary] [Full Text]

To: RevMikeB who wrote (23000)	7/9/1998 8:55:00 PM
From: Henry Niman	Respond to of 32384

RevMikeB, Most of Biotech therapeutics are targets of this breakthough. LGND has shown that a small molecule can replace the large proteins that Biotechs manufacture and inject into patients. Products in this category include insulin, Epogen, Neupogen, Aldesleukin (IL-2), Betaseron, Myotropin, Leptin, Avonex and a wide range of interferons, interleukins, and growth factors under development by many companies.

To: RevMikeB who wrote (23000)	7/9/1998 10:32:00 PM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Today Dow Jones had an extensive article on SBH and potential merger candidates: paradise-web.com

To: RevMikeB who wrote (23000)	7/13/1998 8:39:00 AM
From: Biotech Jim	Read Replies (2) \| Respond to of 32384

Small molecule agonists do not have to be orally bioavailable to be blockbusters. Of course it helps, but how many protein therapeutics are orally active? Also, the cost of goods will a lot less. Well, we go from a question I raised several months ago to a Science paper. I guess the data I like most is that the compound appears to be a full agonist (fig. 6), but not according to fig. 5. Does it block natural G-CSF activity?

To: RevMikeB who wrote (23000)	7/13/1998 9:10:00 AM
From: Henry Niman	Respond to of 32384

Looks like LGND will issue a press release today indicating the its Panretin gel will get a priority review at the FDA.