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

Laia JosaCulleré | Zendy; Katrina S. Madden | Zendy; Thomas J. Cogswell | Zendy; Thomas Jackson | Zendy; Tom S. Carter | Zendy; Douzi Zhang | Zendy; Graham Trevitt | Zendy; Stephen G. Davies | Zendy; Paresh Vyas | Zendy; Graham M. Wynne | Zendy; Thomas A. Milne | Zendy; Angela J. Russell | Zendy

Open Access

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

Author(s) -

Laia JosaCulleré,

Katrina S. Madden,

Thomas J. Cogswell,

Thomas Jackson,

Tom S. Carter,

Douzi Zhang,

Graham Trevitt,

Stephen G. Davies,

Paresh Vyas,

Graham M. Wynne,

Thomas A. Milne,

Angela J. Russell

Publication year - 2021

Publication title -

journal of medicinal chemistry

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.01

H-Index - 261

eISSN - 1520-4804

pISSN - 0022-2623

DOI - 10.1021/acs.jmedchem.1c00574

Subject(s) - phenotypic screening , in vivo , myeloid leukemia , phenotype , chemistry , cellular differentiation , in vitro , leukemia , myeloid , cancer research , cell culture , differentiation therapy , microbiology and biotechnology , immunology , biology , biochemistry , gene , genetics , acute promyelocytic leukemia , retinoic acid

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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