Type II Kinase Inhibitors Library
ChemDiv’s Type ll Kinase Inhibitors Library contains 8,000 compounds.
Type II inhibitors bind to an extended ATP site including a back pocket formed by displacement of highly conserved DFG (Asp-Phe-Gly) motif (‘DFG-out’) at the start of the activation segment of the kinase. This is an inactive conformation.
Advantages of non-ATP site inhibitors or activators:
1) Since binding sites outside the ATP site are less conserved throughout the kinome, it should be possible to make more selective compounds.
2) The variety and novelty of the non-ATP sites provides opportunities to produce novel compounds
3) Resistance arises when mutations prevent the inhibitor from binding. Combination therapy with compounds binding in two different sites can overcome resistance or prevent it from arising.
Type II inhibitors bind to an extended ATP site including a back pocket formed by displacement of highly conserved DFG (Asp-Phe-Gly) motif (‘DFG-out’) at the start of the activation segment of the kinase. This is an inactive conformation.
Advantages of non-ATP site inhibitors or activators:
1) Since binding sites outside the ATP site are less conserved throughout the kinome, it should be possible to make more selective compounds.
2) The variety and novelty of the non-ATP sites provides opportunities to produce novel compounds
3) Resistance arises when mutations prevent the inhibitor from binding. Combination therapy with compounds binding in two different sites can overcome resistance or prevent it from arising.