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Article

Identification and Preliminary Structure-Activity Relationship Studies of 1,5-Dihydrobenzo[e][1,4]oxazepin-2(3H)-ones That Induce Differentiation of Acute Myeloid Leukemia Cells In Vitro

1
Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK
2
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, UK
3
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK
*
Authors to whom correspondence should be addressed.
Academic Editor: Giosuè Costa
Molecules 2021, 26(21), 6648; https://doi.org/10.3390/molecules26216648
Received: 21 September 2021 / Revised: 18 October 2021 / Accepted: 18 October 2021 / Published: 2 November 2021
(This article belongs to the Special Issue Phenotypic Screening)
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. View Full-Text
Keywords: acute myeloid leukemia; differentiation; phenotypic screen; CD11b; benzooxazepinones acute myeloid leukemia; differentiation; phenotypic screen; CD11b; benzooxazepinones
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MDPI and ACS Style

Josa-Culleré, L.; Cogswell, T.J.; Georgiou, I.; Jay-Smith, M.; Jackson, T.R.; Bataille, C.J.R.; Davies, S.G.; Vyas, P.; Milne, T.A.; Wynne, G.M.; Russell, A.J. Identification and Preliminary Structure-Activity Relationship Studies of 1,5-Dihydrobenzo[e][1,4]oxazepin-2(3H)-ones That Induce Differentiation of Acute Myeloid Leukemia Cells In Vitro. Molecules 2021, 26, 6648. https://doi.org/10.3390/molecules26216648

AMA Style

Josa-Culleré L, Cogswell TJ, Georgiou I, Jay-Smith M, Jackson TR, Bataille CJR, Davies SG, Vyas P, Milne TA, Wynne GM, Russell AJ. Identification and Preliminary Structure-Activity Relationship Studies of 1,5-Dihydrobenzo[e][1,4]oxazepin-2(3H)-ones That Induce Differentiation of Acute Myeloid Leukemia Cells In Vitro. Molecules. 2021; 26(21):6648. https://doi.org/10.3390/molecules26216648

Chicago/Turabian Style

Josa-Culleré, Laia, Thomas J. Cogswell, Irene Georgiou, Morgan Jay-Smith, Thomas R. Jackson, Carole J. R. Bataille, Stephen G. Davies, Paresh Vyas, Thomas A. Milne, Graham M. Wynne, and Angela J. Russell. 2021. "Identification and Preliminary Structure-Activity Relationship Studies of 1,5-Dihydrobenzo[e][1,4]oxazepin-2(3H)-ones That Induce Differentiation of Acute Myeloid Leukemia Cells In Vitro" Molecules 26, no. 21: 6648. https://doi.org/10.3390/molecules26216648

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