Heart Failure remains a leading cause of morbidity and mortality worldwide, despite historical advances in treatment. Several reports in the literature have pointed to GRK2 (G protein-coupled receptor kinase 2), a regulator of GPCRs, particularly b-andrenergic receptors, as an attractive target for new therapeutics as it plays a key role in the development and progression of cardiovascular disease. As we prosecuted a program aimed at discovering novel GRK2 inhibitors, we were in parallel exploring ways to accelerate cycle times in lead discovery chem. Taking a page from industry leaders outside of pharma who have consistently demonstrated superiority in the speed, quality, and efficacy of their upstream development and design processes, we piloted news ways of integrating the contributions of matrix team members to generate better answers, quicker, and easier. The identification and optimization of a novel GRK2 hit series will be presented along with key learnings from our high velocity learning pilot.