https://www.selleckchem.com/products/r428.html The search is on for effective specific inhibitors for PI3Kα mutants. PI3Kα, a critical lipid kinase, has two subunits, catalytic and inhibitory. PIK3CA, the gene that encodes the p110α catalytic subunit is a highly mutated protein in cancer. Dysregulation of PI3Kα signalling is commonly associated with tumorigenesis and drug resistance. Despite its vast importance, only recently the FDA approved the first drug (alpelisib by Novartis) for breast cancer. A second (GDC0077), classified as PI3Kα isoform-specific, is undergoing clinical trials. Not surprisingly, these ATP-competitive drugs commonly elicit severe concentration-dependent side effects. Here we briefly review PI3Kα mutations, focus on PI3K drug repertoire and propose new, to-date unexplored PI3Kα therapeutic strategies. These include (1) an allosteric and orthosteric inhibitor combination and (2) taking advantage of allosteric rescue mutations to guide drug discovery.Emulsification of elemental mercury in aqueous solution in the form of grey particles occurs upon exposure to intense sound fields. We show the concomitant formation of molecular Hg(OH)2 in the solution phase reaching a saturation limit of 0.24 mM at 25 °C. The formation of Hg(OH)2 is consistent with the 'hot spot' model which suggests the formation of OH˙ as a result of acoustic cavitation; such radicals are proposed to combine with Hg to form the Hg(OH)2 species here characterised using voltammetry.Scandium-44 has emerged as an attractive, novel PET radioisotope with ideal emission properties and half-life (t1/2 = 3.97 h, Emean β+ = 632 keV) well matched to the pharmacokinetics of small molecules, peptides and small biologics. Conjugates of the current gold-standard chelator for 44Sc, 1,4,7,10-tetraaza-cyclododecane-1,4,7,10-tetraacetic acid (DOTA), require heating to achieve radiochemical complexation, limiting application of this isotope in conjunction with temperature-sensitive biologics. To e