Kinase Chemistry – Just a year and a half behind the times.


Posted by kinasepro on June 21, 2007

Kinex filed an IND today for this ‘ere compound:


KX-01, KX2-391, ALB-30350, wait, ALB-30350? yah…

from WO/2006/071960:

Note that KX2-391 has weak activity against isolated kinases because the peptide binding site is not well formed outside of cells (a close analog, KX2-394 is a little more potent against isolated Src [KP note: 394 is the piperazine]), but have very potent activity inside whole cells. Without wishing to be bound by theory, it is thought that the difference in activity is attributed to the fact that the peptide binding site is now fully formed in cells due to the allosteric effects of the binding protein partners in the multi-protein signaling complexes, relative to isolated kinase assays.

10 Responses to “KX2-391”

  1. Wijit said

    I wonder what the clearance is? Looks vulnerable to high first pass metabolism to me.

  2. Reminds me of some work that dealt with similar effects but different causes, done by Shokat. (Chem Biol 05) In that case, two kinase inhibitors had certain relative potencies in vitro, that were completely reversed in vivo, because one pathway was more ‘sensitive’ than the other.

  3. milkshake said

    the point is that biochemical assays with a purifiead and often incomplete protein construct are pretty artificial and cannot be relied upon, especially in the late stages of the project. Cell-based assays are the real deal/

  4. kinasepro said

    I’m a little hard-nosed when it comes to this sort of thing… The application does have some data, but nothing on how they conclude the compounds are atp-non competitive. Xray? kinetic experiments? molecular modeling?

  5. milkshake said

    the difficulty is that they don’t have to provide much data as evidence for their claims in patent application. I have seen (and took part myself in) the patents submissions that claimed that all described compounds had “EC50 better than 5 micromolar”.

  6. weirdo said

    Far more likely is that the cellular effect has nothing to do with their putative target. They just don’t know the real target.

    That, or the molecule is accumulating in the cells.

    Either way, “unanticipated toxicity” is likely the next press release.

  7. kinasepro said

    Maybe it’s same target as that unkown Lexicon target !? Whatever it hits, its likely derived from:


  8. xtallographer said

    looks like a channel blocker to me….

  9. Moustafa El-Araby said

    Well, the molecule has survived phase-I trials and won SBIR for about 1 million in May 2009 to pusue Phase II. I believe in this molecule which has very interesting story I know very well because………..
    Dave Hangauer is a great scientist and very kind person as well.

  10. petros said

    The ASCO presentation of the Phase I data mentions a second, unidentified, mode of action.

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