NVP-CLR457 (Novartis Institutes for BioMedical Research) is an oral, non-CNS-penetrating pan-class IA phosphoinositide 3-kinase (PI3K) inhibitor . This is a great teaching example for medicinal chemistry as the authors of the recent paper explain their thought process for lead optimization in depth. The molecule was nominated by reviewer Julien Lefranc, who helped note several key points here.