Hit expansion

Following hit confirmation, several compound clusters will be chosen according to their characteristics in the previously defined tests. An Ideal compound cluster will contain members that possess:

high affinity towards the target (less than 1 μM)

selectivity versus other targets

significant efficacy in a cellular assay

druglikeness (moderate molecular weight and lipophilicity usually estimated as ClogP). Affinity, molecular weight and lipophilicity can be linked in single parameter such as ligand efficiency and lipophilic efficiency.

low to moderate binding to human serum albumin

low interference with P450 enzymes and P-glycoproteins

low cytotoxicity

metabolic stability

high cell membrane permeability

sufficient water solubility (above 10 μM)

chemical stability

synthetic tractability

patentability

three and six compounds selected to be further explored. Next: Quantitative structure-activity relationship (QSAR)

For NH125