Michael G. Darcy

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: A biochemical RNA synthesis assay was established to identify potential polymerase inhibitors from a high throughput screen of the GlaxoSmithKline proprietary compound collection, finding the benzo-1,2,4-thiadiazine compound 1 to be a potent, highly specific inhibitor of NS5B.

TL;DR: GSK2830371 is the first orally active, allosteric inhibitor of Wip1 phosphatase, an oncogenic phosphat enzyme common to multiple cancers and results in expected pharmacodynamic effects and causes inhibition of lymphoma xenograft growth.

TL;DR: The structure-activity relationships (SAR) of substituents on the quinolinone ring will be focused on, culminating in the discovery of 1-(2-cyclopropylethyl)-3-(1,1-dioxo-2H-1,2,4-benzothiadiazin-3-yl)-6-fluoro-4-hydroxy-2(1H)-quinolinone (130), an inhibitor with excellent potency in biochemical

TL;DR: Modification of the core structure and adjustment of unwanted functionality resulted in the development of (5-oxo-1,5-dihydropyrazol-4-ylidene)hydrazines which exhibited efficacies equivalent to those of TPO in several cell-based assays designed to measure thrombopoietic activity.