First-in-Human Study of AT13148, a Dual ROCK-AKT Inhibitor in Patients with Solid Tumors.
Robert McLeodRajiv KumarDionysis Papadatos-PastosJoaquin MateoJessica S BrownAlvaro H Ingles GarcesRuth RuddleShaun DecordovaSimone JueligerRoberta FerraldeschiOscar MaiquesVictoria Sanz-MorenoPaul JonesStephanie TraubGavin W HalbertSarah MellorKaren E SwalesFlorence I RaynaudMichelle D GarrettUdai BanerjiPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2020)
AT13148 was the first dual potent ROCK-AKT inhibitor to be investigated for the treatment of solid tumors. The narrow therapeutic index and the pharmacokinetic profile led to recommend not developing this compound further. There are significant lessons learned in designing and testing agents that simultaneously inhibit multiple kinases including AGC kinases in cancer.