Schmidt Stanley J

TL;DR: 2,4-Difluoro-N-{2-(methyloxy)-5-[4-(4-pyridazinyl)-6-quinolinyl]-3- pyridinyl}benzenesulfonamide (GSK2126458, 1) has been identified as a highly potent, orally bioavailable inhibitor of PI3Kα and mTOR with in vivo activity in both pharmacodynamic and tumor growth efficacy models.

TL;DR: Crystallographic and biochemical results demonstrated that compounds of this chemical series bind to an allosteric site and lock the enzyme in a catalytically inactive conformation, thereby enabling inhibition of different clinically relevant IDH1 mutants.

TL;DR: In this article, a method of inhibiting the activity/function of PI3 kinases using quinoline derivatives was proposed, which is a method for treating one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries.

TL;DR: Key to the advancement of the series was the introduction of a 2-aryl group containing a basic amine onto the azaindole leading to significantly improved cellular activity leading to the identification of GSK1070916 (17k), a potent and selective ATP-competitive inhibitor of Aurora B and C.

TL;DR: The discovery of a selective chemotype for PI3K isoforms from a three-cycle DNA encoded library was made and an X-ray crystal structure of a representative inhibitor from this chemotype demonstrated a unique binding mode in the p110α protein.