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

Postcards from Vienna…

Posted by kinasepro on October 1, 2008

Hey look what I got:

Yah, its the disclosure of the discovery of PHA-848125.  Not only that, its a pretty good poster. This also means I was wrong again!


7 Responses to “Postcards from Vienna…”

  1. milkshake said

    We had gem-dimethyl substitted cyclohexane-fused pyrrole-oxindole compound of Sutent structure class back in early 2000s. The gem-dimethyl greatly improved the selectivity – it seems that CDKs have much more room in their binding site.

    I faintly remember that our series were pretty good but eventually the whole CDK progrm fell out of favor for biology reasons and they transferred most people on c-Met.

  2. kinasepro said

    Nerviano’s got a nice story, and decent bioavailability. I’ll admit I stopped reading when I heard its equipotent on TrkA though.

  3. Orgmed said

    Nice data. 98% PPB?. Claim to be improved PK/PD. Not understood what the formulation could be.

  4. ppp said

    KinasePro: why so negative on TrkA?

  5. Orgmed said

    I guess most of the kinase inhibitors these day’s exhibit TrkA activity. Looks like it hard to find a scaffold that do not exhibit TrkA and for Flt3?.

  6. kinasepro said

    Ehhm, no.

    TrkA is a peculiar target, but the world has seen so many CDK inhibitors come and go that one without a defining selectivity profile leaves me wanting more.

  7. ppp said

    What do you mean by “defining selectivity profile”? A compound that hits CDKs and TrkA in a panel of some dozens kinases (Ok, what about the other ca. 480, but this i sthe same for any other kinase inhibitor) may be selective enough to hit the market (on the other side, Sunitinib that it is much less selctive did it). I argue that that the biochemical selectivity profile is something good to know to weed out staurosporine-like compounds but then the answer is the activity/safety ratio (in animals first then in the clinic) which is somewhat unpredictable from the in vitro profile.

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: