Christian S. Sherk

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: The discovery of GSK3685032 is reported, a potent first-in-class DNMT1-selective inhibitor that was shown via crystallographic studies to compete with the active-site loop ofDNMT1 for penetration into hemi-methylated DNA between two CpG base pairs.

TL;DR: A novel thiazolopyrimidinone series of PI3K-beta selective inhibitors has been identified and provided an excellent tool compound that showed potent growth inhibition in the PTEN-deficient breast cancer cell line MDA-MB-468 under anchorage-independent conditions.

TL;DR: The role of GSK3052230 in effectively targeting FGF-FGFR autocrine signaling in mesothelioma is supported, its impact on tumor growth and angiogenesis is demonstrated, and a rationale for the current clinical evaluation of this molecule is provided.

TL;DR: It is demonstrated that selective, non-covalent inhibitors of DNMT1 may provide benefit over traditional DNA incorporating hypomethylating agents.