Baird,
<<If "pool and split" is likely to generate more leads, does that suggest that PCOP
will likely develop the larger library of compounds that in turn will generate more partnerships more leads?>>
I think that is a correct conclusion, with the caveat that the libraries must have a reasonable degree of variety {the buzzwords in the industry for this are "molecular diversity" and "exploration of pharmacophoric space"}. So, bigger is not NECESSARILY better -- Parke-Davis' subsidiary found that out. To find a lead, you not only need to make a lot of compounds, but you also need to make a lot of compounds that have different functional groups and sweep out different areas of space.
I think PCOP is doing just that.
In theory, "contamination" (if you mean, mixing two different target molecules) should be a rarity in the split and pool approach, because the final products are not liberated from the bead (or micro-reactor or what-have-you) until the final step, and (usually!) in separate vessels. However, one also doesn't know what one actually has until the end (you probably don't want to know about solid phase NMR of compounds on beads at this point).
"Easier to index" is not necessarily better. It is not important to know, at the testing stage, what one is testing in a lead-finding program. As long as you can, with a little effort, figure out what the active compounds are, you're golden.
Here's a way for a non-chemist to think about pool and split.
Take a rock and tie it to a blue Lego piece with some string. Do the same with red, yellow, and green Lego pieces. For each rock, paint a B for blue, R for red, etc. Now, give all four of these rocks to a technician and tell him (or her) to put a blue Lego on all existing Legos and paint a B on all of the rocks -- you now have four rocks labelled BB, RB, YB, GB. Do it again with red -- BBR, RBR, YBR, GBR. Do it again with yellow. Now, separate all the rocks. Take a rock now. You can tell what Lego structure you (should!!) have by looking at the rock (BBRY, for example). Cut the string and throw away the rock. You now have a Lego ("target molecule" or "compound") and you should know what it is based on the painting ("tagging") of the rock from which you cut it. As long as you have carefully separated all the rocks (easy to do), there will no cross-contamination.
I hope this helps you get a better grasp of the technology involved -- I apologize if this is too basic an explanation.
I am still gathering info on combichem companies for my own interests and when I get it in a form that is coherent I'll let you know what I found out. Off the top of my head, Arqule and PCOP are tops -- Versicor looks great (I don't think they're public, but a subsidiary of Sepracor). |
