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

To: squetch who wrote (10569)	10/31/1997 10:27:00 PM
From: Henry Niman	Read Replies (1) \| Respond to of 32384

Stan, The screening process is fairly straight forward. As I recall, beginning in 1991 LGND screened PFE's entire library in 23 months and received at $500,000 bonus for finishing ahead of schedule. I suspect that today the screening is considerably faster. The receptor of interst is in the cell line which has a reporter gene attached to the hormone response element. For the drug to register as a positive, it must enter the cell, cause the receptor to undergo a conformational change which "activates" it. The activated receptor then goes to the nucleus of the cell and turns on the reporter gene (I think its luciferonase) which then emits light which is picked up with a plate reader. 96 well plates are used so 96 compounds can be screened per plate. I think that LGND uses robots to run the entire process. For antagonists, an agonist is added first and then the cells are screened for a dimunition of the signal. The constructs can be placed in different cell types to study the interactions with various cell specific transcription combinations. The screening is disease independent. LGND initially looks for drugs that can appropriately activate a receptor. The drug is generally screened agains a panel of receptors. For most of the alliances, LGND's partner gets to develop the drug for the indication of interest (i.e. osteoporosis). LGND however can license the compound for development for other indications (i.e. breast cancer).