Josa-Culleré, Laia, Cogswell, Thomas J., Georgiou, Irene, Jay-Smith, Morgan, Jackson, Thomas R., Bataille, Carole J. R., Davies, Stephen G., Vyas, Paresh, Milne, Thomas A., Wynne, Graham M., and Russell, Angela J.
Acute myeloid leukemia (AML) is the most aggressive type of blood cancer, and there is a continued need for new treatments that are well tolerated and improve long-term survival rates in patients. Induction of differentiation has emerged as a promising alternative to conventional cytotoxic chemotherapy, but known agents lack efficacy in genetically distinct patient populations. Previously, we established a phenotypic screen to identify small molecules that could stimulate differentiation in a range of AML cell lines. Utilising this strategy, a 1,5-dihydrobenzo[e][1,4]oxazepin-2(3H)-one hit compound was identified. Herein, we report the hit validation in vitro, structure-activity relationship (SAR) studies and the pharmacokinetic profiles for selected compounds. [ABSTRACT FROM AUTHOR]