Grace Q Gong, Benoit Bilanges, Ben Allsop, Glenn R Masson, Victoria Roberton, Trevor Askwith, Sally Oxenford, Ralitsa R Madsen, Sarah E Conduit, Dom Bellini, Martina Fitzek, Matt Collier, Osman Najam, Zhenhe He, Ben Wahab, Stephen H McLaughlin, A W Edith Chan, Isabella Feierberg, Andrew Madin, Daniele Morelli, Amandeep Bhamra, Vanesa Vinciauskaite, Karen E Anderson, Silvia Surinova, Nikos Pinotsis, Elena Lopez-Guadamillas, Matthew Wilcox, Alice Hooper, Chandni Patel, Maria A Whitehead, Tom D Bunney, Len R Stephens, Phillip T Hawkins, Matilda Katan, Derek M Yellon, Sean M Davidson, David M Smith, James B Phillips, Richard Angell, Roger L Williams, Bart Vanhaesebroeck
Harnessing the potential beneficial effects of kinase signalling through the generation of direct kinase activators remains an underexplored area of drug development1-5 . This also applies to the PI3K signalling pathway, which has been extensively targeted by inhibitors for conditions with PI3K overactivation, such as cancer and immune dysregulation. Here we report the discovery of UCL-TRO-1938 (referred to as 1938 hereon), a small-molecule activator of the PI3Kα isoform, a crucial effector of growth factor signalling...
May 24, 2023: Nature