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Assays
Richard Eglen: Or even if it’s a hit. at all? So that needs to be decided. I still remember
the days when measuring change in muscle con-
Martina Bielefeld-Sevigny: Generally it could be tractions was a readout for GPCRs.
said that there are only a few GPCRs that are suc-
cessful drug targets. There’s only a certain group Robert Jordan: That’s a pretty good readout.
around the drug targets, or don’t we have the
methodology to detect that they are? Or did we Richard Eglen: It’s not bad! They’ve found some
target in the past always the easy ones? And the very successful billion-dollar drugs. The point is,
complex ones, we don’t just have the methods to now of course, one has to deconvolute how did it
find them? modulate that particular physiological response to
its mode of action? Which is why I raise things like
Kevin Pfleger: I mean the chemo guys are a good the label free. Are you looking at some holistic
example. They’re not aware of any compounds, change that maybe we’re not too worried about
everybody’s looking at them... how it’s doing it as long as it does it. So I would say
at least from our perspective we’re developing a
Martina Bielefeld-Sevigny: So GPCRs can really range of assays for a range of different systems
come back as drug targets. We really see that it’s seems to be what people want instead of a univer-
going down and why is it going down? sal cure type of technology. Maybe when there’s
crystal structures, maybe when there’s docking
David Marks: I don’t think it’s ever gone down, type things developed, that may change some
based on our own experience internally. It’s never things, but perhaps not yet.
gone down. We’ve always had GPCR targets every
year. David Marks: You have the crystal structures. I
would argue that still doesn’t change the need for
Martin Valler: For us it’s a major part of the GPCR assays that are coupled to different path-
pipeline and it’s remained so for some time. ways, so you can measure its activity through dif-
ferent pathways – you still need that to understand
Arthur Christopoulos: The 30 percent that every- what changes in the structure interaction mean in
one quotes of drugs on the market attributed to signal transduction.
GPCRs they’re almost all Family A. All these oth-
ers, and there’s still quite a number of Family A’s Richard Eglen: I mean, Guido, you do a range of
that haven’t been tapped, but there’s no shortage of assays in your setup?
GPCRs to drug, I think.
Guido Zaman: Yes, we prefer to screen with pri-
David Marks: I still think a lot more work on mary assays for physiological relevant readout,
Family B as well. and still an artificial readout can be very useful in
the primary realm, but then we are going to con-
Robert Jordan: Talking about the vendors. Do you firm and test particular lead compounds in a range
think it’s feasible, or even warranted, to develop a of signals and possibilities. With respect to label
universal cellular assay platform for GPCRs free technology, I also think for now, this can be
around one technology? As some vendors seem to placed when you have a lead series that you know
be suggesting it’s possible to do. modulates a certain target but you want to confirm
it for physiological relevance, then that indeed does
Richard Eglen: Speaking as a vendor... I’ll get my what you want it to….
retaliation in first. Our perception at least is you
can have what are promoted as universal assays but Martin Valler: Is there any advantage to having
I suspect, as something David said earlier, is that multiple assays as well? At this stage, nobody’s got
many people want to take a battery of approaches the full answer. It would be very risky to say this is
to screening that either narrow things down to a the one assay that will deliver... the general feed-
discrete pathway, or a different mode of measuring back is do you want more information in this situ-
the interaction, and then do the cross-calibration. ation which is becoming complex not less complex
Because quite clearly now as one develops separate and every day you get different ideas and feedback.
panels of assays, one is finding different libraries of I think people want more information, not less.
compounds emerging as leads. And the question is,
are these all new varieties of leads, or are they leads Kevin Pfleger: I say you’ve got two ways to go with
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