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Re: mcbio post# 85363

Saturday, 10/24/2009 12:01:44 AM

Saturday, October 24, 2009 12:01:44 AM

Post# of 253527
I'd never heard of this PCYC program until your post. Btk is indeed downstream of SYK (inasmuch as anything in these systems with feedback loops and redundant pathways can be said to be downstream of something else), so I could imagine inhibiting it might have fewer side effects.

This article gives some insights into the connection between SYK and Btk:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC16561/

On looking further, I would have some long-term tox concerns, as it seems Btk is a negative regulator of the Wnt-beta-catenin pathway:

http://www.ncbi.nlm.nih.gov/pubmed/19471023

The Wnt-beta-catenin pathway is crucially upregulated in initial colon cancer, raising an obvious concern.

I think the bottom line is that there are unknown risks involved in chronically intervening in any of these complex immunological pathways in non-fatal conditions. (Tysabri is of course a poster child for just such an unknown risk.) So maybe second or third to market with a better drug is the smarter general strategy.

Whether I might ever be tempted to even remotely consider investing in PCYC depends on how thoroughly they fumigated the place after the previous management departed. :)

Peter

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