A Phenotypic Screen Identifies a Compound Series That Induces Differentiation of Acute Myeloid Leukemia Cells In Vitro and Shows Antitumor Effects In Vivo

J Med Chem. 2021 Nov 11;64(21):15608-15628. doi: 10.1021/acs.jmedchem.1c00574. Epub 2021 Oct 21.


Induction of differentiation is a promising therapeutic strategy against acute myeloid leukemia. However, current differentiation therapies are effective only to specific patient populations. To identify novel differentiation agents with wider efficacy, we developed a phenotypic high-throughput screen with a range of genetically diverse cell lines. From the resulting hits, one chemical scaffold was optimized in terms of activity and physicochemical properties to yield OXS007417, a proof-of-concept tool compound, which was also able to decrease tumor volume in a murine in vivo xenograft model.

Publication types

  • Research Support, Non-U.S. Gov't