Richard R. Gontarek

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: Activity against c-kit and Flt-3 by multikinase angiogenesis inhibitors provide a potential explanation for the differences in myelosuppression observed with these agents in patients.

TL;DR: Comparative studies identified a network of remote interactions around the PTC, indicating that pleuromutilin selectivity is acquired by nonconserved nucleotides residing in the P TC vicinity, in a fashion resembling allosterism.

TL;DR: Interestingly, the phosphorylated IRS-1 (insulin receptor substrate-1) protein shows activation of the lipid Kinase activity for the wt and H1047R but not E542K and E545K PI3Kα, suggesting that these mutations represent different mechanisms of lipid kinase activation and hence transforming activity in cancer cells.

TL;DR: A potent, selective, reversible, ATP-competitive inhibitor of Plk1, GSK461364A, capable of inhibiting cell growth of most proliferating cancer cell lines tested is identified and observed.