| abstract |
An ATP non-competitive inhibitor of mitogen-activated protein kinase (MEK), inter alia, human MEK (MEK1 or MEK2) having the properties: (i) allosterically binds an inhibitor pocket formed at an interaction interface between human MEK (MEKl or MEK2) and human Kinase Suppressor of Ras (KSR1 or KSR2 or BRAE) adjacent to ATP in a physiological complex between MEK and KSR (or BRAE), forming an inhibitor-inhibitor pocket complex; (ii) is an ATP non-competitive kinase inhibitor; (iii) a structure such that when bound to the inhibitor-inhibitor pocket complex, the complex comprises the structural elements:(a) at least one moiety of the inhibitor engaging A825 of KSR1, or P878 of KSR2; or R662 of BRAE (b) at least one moiety engaging R234 of MEK, wherein where R234 is within 5 Å from any atoms of KSR1 or KSR2 or BRAE is disclosed. |