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Re: biocrio post# 9591

Saturday, 04/02/2005 2:59:39 PM

Saturday, April 02, 2005 2:59:39 PM

Post# of 257369
Honestly, just because Geneara (or any company) puts out a PDF presentation with a slide showing that VEGF, bFGF etc... signaling pathways are all antagonized by squalamine is not proof that the mechanism has been clarified.

First of all, no professional scientific presentation uses "etc..." when discussing signaling pathways smile

Second of all, calmodulin is one of the most abundant protein in cells, challenging the concept of specificity. Plus, some of the common assays used by Geneara (as with other companies) are really tissue culture-specific events. Stress fibres are really an in vitro phenomenon, and it is unclear what role the dissolution of stress fibres has in vivo.

Also, I can't find any data on pubmed describing the apoptotic effects of squalamine.

In short, I personally don't find this presentation to be informative scientifically. Possibly Genaera has more information in-house to support their claims. However, I don't see this presentation to be any more clear or any less clear than presentations from other companies using compounds that were not designed de novo for a known target. It is actually a difficult endeavour to find the target of a previously uncharacterized drug, so the only way to start is to begin by examining well known and often implicated pathways (VEGF or MAPK, for example) and hope that something pops up... that's why, for most drugs without prior MOA data, you'll often see that the early experiments show them implicated in VEGF signaling or MAPK signaling. That's because these pathways are almost universally implicated and are the first ones that labs "test" when trying to get a handle on the method of action.

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