Subject: What is a good screening conc. for HTS

From: Iain M McLay <[email-masked]>
Date: Thu, 13 Mar 1997 23:47:29 +0000

I hope you don't mind me using the CCL to ask this question, I believe 
that many readers working in the pharmaceutical industry may be asking 
themselves this question and I would like to see if there is some kind 
of industry consensus.

In my company, Rhone Poulenc Rorer UK, we are often involved in a 
fascinating debate as to whether it is worth screening at high 
micromolar concentrations or not for a receptor antagonist.

The argument against goes something like "a high micromolar lead is 
likely to be non-specific and very difficult to turn into a nanomolar 
final compound, we are making life hard for ourselves so screen at 
<10micromolar"
The argument in favour goes something like "as long as the compound is 
competitive and reversible there is no reason why this cannot be turned 
rapidly into a nanomolar compound. Some targets are very difficult to 
find leads for and we cannot risk missing anything, so screen at 
>30micromolar"

We are often told Pfizer never screens at more than 1micromolar or Glaxo 
always screens at 40micromolar, what is the truth. At my centre we have 
used both approaches depending on the beliefs of the project 
controllers, does this happen with other companies?

For now I'll resist stating my own opinion as it might effect the 
debate.

Thanks,

Iain

Iain M McLay
e-mail [email-masked]