Master Keys from the NCL library

Considering the structural features of the Kinom Tree and the existing homologies in the kinase families we have developed 23 Master Keys from our NCL library which practically cover the whole Kinom. We utilize these Master keys for hit finding and as starting points in developing novel inhibitors for selected targets and to study the binding modes of inhibitors to a particular kinase family.

From a thorough structural and functional analysis of kinase structures, a modular chemistry concept emerges in which specifically functionalized heterocyclic core structures account for a pronounced family-wide requirement for ATP-binding, namely the formation of a hydrogen bond duplex or triplex to the so-called hinge part present in each and every kinase, while specificity-mediating binding elements are attached to well-elaborated and positioned functional groups on the molecular scaffold of the parent privileged structure in order to gain the required selectivity profile.

From the given privileged structure or Master Key a lead compound can be generated with a well defined optimization process, considering orientation characteristics, modular chemistry, solubility, permeability, metabolic stability, IP position and other parameters.