Ken A. Newlander

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: Results show that GSK1070916 is a potent Aurora B/C kinase inhibitor that has the potential for antitumor activity in a wide range of human cancers.

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: In a murine xenograft model with HCT116 D130V tumors, 20 showed significant antitumor activity following intraperitoneal dosing, providing in vivo proof-of-principle of the efficacy of an ATP-competitive KSP inhibitor versus tumors that are resistant to the other known KSP inhibitors.

TL;DR: The enzymatic characterization of a potent and selective AurB/AurC inhibitor is reported, which is a reversible and ATP-competitive inhibitor of the AurB-INCENP (inner centromere protein) enzyme.