We recently reported the discovery of AM-8553 (1), a potent and selective piperidinone
inhibitor of the MDM2–p53 interaction. Continued research investigation of the N-alkyl …

Empirical force fields, or molecular mechanics meth-ods, have been developed for the
investigations of structures and conformations of molecules. Extensions to molecular dynamics …

p53 is a critical tumor suppressor and is the most frequently inactivated gene in human
cancer. Inhibition of the interaction of p53 with its negative regulator MDM2 represents a …

We previously reported the discovery of AMG 232, a highly potent and selective piperidinone
inhibitor of the MDM2–p53 interaction. Our continued search for potent and diverse …

JAK (Janus family of cytoplasmic tyrosine kinases) family tyrosine kinase 2 (TYK2) participates
in signaling through cytokine receptors involved in immune responses and inflammation. …

We describe the structural optimization of a lead compound 1 that exhibits dual inhibitory
activities against FLT3 and CDK4. A series of pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidine …

Structure-based rational design and extensive structure–activity relationship studies led to
the discovery of AMG 232 (1), a potent piperidinone inhibitor of the MDM2–p53 association, …

The performance of docking studies into protein active sites constructed by homology model
building was investigated using CDK2 and factor VIIa screening data sets. When the …

We previously reported the discovery of potent and selective morpholinone and piperidinone
inhibitors of the MDM2-p53 interaction. These inhibitors have in common a carboxylic acid …

The discovery, structure-based design, synthesis, and optimization of NIK inhibitors are
described. Our work began with an HTS hit, imidazopyridinyl pyrimidinamine 1. We utilized …