Posted by kinasepro on April 19, 2007
362 examples, 15 inventors.
IND beating first app is unusual. kudos.
Wild speculation mode on: The Azetidine 3-hydroxyl residue directly coordinates the Mg atom.
This class of molecules is the closest thing that can be considered allosteric inhibitors of kinases. (No, I don’t care about your 18 uM compounds) They have been called ATP non-competitive, but perhaps more accurately I consider them ATP-collaborative inhibitors, given that they appear to hydrogen bond to ATP within the active site. As such I have a hard time considering them truly allosteric. 1S9I, and 1S9J give an idea how they work.
al·lo·ster·ism (l-strzm) or al·los·ter·y (-lst-r)
n. A change in the activity and conformation of an enzyme resulting from the binding of a compound at a site on the enzyme other than the active binding site.