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

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.
Laia Josa-Culleré 1,  Katrina S Madden 1,  Thomas J Cogswell 2,  Thomas R Jackson 3,  Tom S Carter 1,  Douzi Zhang 3,  Graham Trevitt 4,  Stephen G Davies 1,  Paresh Vyas 3,  Graham M Wynne 1,  Thomas A Milne 3,  Angela J Russell 1 2
Affiliations

Affiliations

  • 1 Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, U.K.
  • 2 Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, U.K.
  • 3 MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, NIHR Oxford Biomedical Research Centre Haematology Theme, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, U.K.
  • 4 XenoGesis Ltd., BioCity Nottingham, Pennyfoot Street, Nottingham NG1 1GF, Nottinghamshire, U.K.
PMID: 34672555 DOI: 10.1021/acs.jmedchem.1c00574
Abstract

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.

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    Product Name
    Description
    Target
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  • HY-139877
    Anticancer Agent