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


Posted by kinasepro on December 26, 2006

Entremed has an ‘Aurora A selective’ preclinical candidate ENMD-981693, which is likely MKC-1693 or closely related. Here’s a poster given earlier this month. The structure has not been divulged, but the compound most likely came from the purchase of Miikana’s IP. There’s only one Miikana publication on Aurora and its the patent application: WO2006055831 which comprise a series of amides (and esters):

look familar?

So lets review:

  VX680 (nM) ENMD-981693 (nM)
Aurora A 0.6 15
Aurora B 18 290
Aurora C 4

Don’t get me wrong I’m all for subtle modifications yeilding better compounds, and certainly the amino group snuggling up to the hinge is an unexpected modification, but I’m just not seeing how this compound is going to beat Vertex. Its slightly more selective then VX680 being 50 fold off Aurora B rather then 30 fold. Cellular numbers could magnify that, but I’m tempted to think that this is just a weaker version of VX-680, else they would have run them head to head and reported why this is better. In this line of work though, unless your really confident, you don’t actually want to run them head to head – since if the competitor wins, your stuck having to report that during any diligence meetings.

>>  update >> They more or less disclosed the structure of their candidate:  check here.


3 Responses to “ENMD-981693”

  1. ebola1 said

    Biochemical data not so important in Aurora inhibitors — The VX-compound shows an Aur B phenotype in vivo and in cells. The selectivity may not be as important as knocking out the activity in cells. Millenium has great selectivity in cells and is likely one of the best Aur A inhibitors to date.
    Also — looking through the kinase profiling — some serious mechanistic assays are going to have to derive the target activity (or combination of)

  2. kinasepro said

    There’s also already an ‘expert opinion‘ on the Millenium compound.

  3. ebola1 said

    Check the cell cycle of every analog — there are some interesting residual checkpoints.

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