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!
This entry was posted on October 1, 2008 at 11:48 am and is filed under CDK, Nerviano.
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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.
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.