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Kinase Inhibitors: Selectivity

(2007-11-05 15:50:16) 下一个

There are a handful of ways to visualize selectivity among kinase inhibitors after you’ve had them Profiled.

The gold standard has become the Ambit panel:

 

(from the Nature Biotech paper)

A simple chart will get the job done:

(INNO-406 / NS-187, from Blood 05, 3948)

or a heat map like Amphoras’:

If you prefer a reductionist approach you’ve always been able to take it down to a single number with fold shift from its nearest neighbor.

And now it looks like there may be a statistically more meaningful number with the recent J Med Chem on applying the Gini Coefficient to kinase inhibitor selectivty. In case you missed it, check out the spreadsheet in the supporting info.

6 Responses to “Selective vs. Nonselective”

  1. on 25 Oct 2007 at 9:40 pm Stoney

    When you say “The gold standard has become the Ambit panel” are you referring to the way in which they represent selectivity/potency on the “Manning tree”, or the Ambit method itself? I don’t know that I would trust selectivity data obtained against binding to phage-displayed kinase domains, which seems several steps removed from activity assays against (one would hope) more rigorously characterized soluble kinases.


  2. on 25 Oct 2007 at 10:11 pm kinasepro

    The visualization method is irrelevant imo… heh… But I do think people have become familiar with that image. From my perspective they are the standard because they have the most kinases and its cheaper to run their panel.

    I think everybody knows that the Kd’s don’t make any sense, and that Upstate isn’t far behind on the numbers game.


  3. on 26 Oct 2007 at 4:50 am Pablo

    ..and what about kinobeads (Nat. Biotech. 2007, 25(9), 1035-1044)?Cellular level..with all the pros and cons.


  4. on 26 Oct 2007 at 10:42 am DrSnowboard

    But hey, aren’t all the successful kinase inhibitors the less selective ones?


  5. on 26 Oct 2007 at 11:01 am Pablo

    Although there are good reasons for targeting several kinases at the same time (at least in Oncology) I’d avoid touching things like PKA, TAK1, LKB-1, DAPK-1 etc.


  6. on 29 Oct 2007 at 10:23 am Petros

    But for other indications selectivity is much more essential

    Look at the problems of p38 inhibitors

    And how will GSK-3 inhibitors, for Alzhimer’s, look on such a diagram?

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