Vertex and c-Met
Posted by kinasepro on June 12, 2007
A reader asks what’s up with these, which got me wondering the same. An interesting new c-Met application from Vertex (WO/2007/064797) likely stems from a screening hit off of a related GSK3 series: WO/2004/058769.
There are a number of examples trying to get away from the phenol, things like prodrugging, and as many isosteres as you shake a stick at. A few interesting modifications appear to produce < 100 nM Ki compounds.
As for how they bind? Well… your guess is as good as mine, but here’s mine: (oops – it’s since come out that the phenol in this motif hits the hinge. so this was a cute idea but wrong)
Just what’s up with the phenol? I have some ideas, but its kind of tricky to guess given the mobility of the a-loop.