Kui Lin

TL;DR: It is shown that silencing Akt1 alone, or any combination of Akt isoforms, can suppress the growth of tumors established from phosphatase and tensin homologue–null human cancer cells, and suggests that blocking lysosomal degradation can be detrimental to cancer cell survival when autophagy is activated.

TL;DR: GDC-0068 is a highly selective, orally bioavailable Akt kinase inhibitor that shows pharmacodynamic inhibition of Akt signaling and robust antitumor activity in human cancer cells in vitro and in vivo.

TL;DR: Biological studies with one 6,7-dihydro-5H-cyclopenta[d]pyrimidine compound, 28 (GDC-0068), demonstrate good oral exposure resulting in dose-dependent pharmacodynamic effects on downstream biomarkers and a robust antitumor response in xenograft models in which the phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin pathway is activated.

TL;DR: A new model of kinase regulation is supported, wherein nucleotides modulate an on-off switch in Akt through conformational changes, which is disrupted by ATP-competitive inhibitors.

TL;DR: Potent inhibition of AKT signaling with ipatasertib was associated with a tolerable safety profile and meaningful disease control in a subgroup of patients, and Targeting pAKT with an ATP-competitive inhibitor provides a greater therapeutic window than allosteric inhibitors.