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

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 chemother...

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Autores principales:	Laia Josa-Culleré, 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, Angela J. Russell
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	acute myeloid leukemia differentiation phenotypic screen CD11b benzooxazepinones Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/371c3b38b9e44be49d8dc114324e28ce
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spelling	oai:doaj.org-article:371c3b38b9e44be49d8dc114324e28ce2021-11-11T18:36:46ZIdentification and Preliminary Structure-Activity Relationship Studies of 1,5-Dihydrobenzo[<i>e</i>][1,4]oxazepin-2(3<i>H</i>)-ones That Induce Differentiation of Acute Myeloid Leukemia Cells In Vitro10.3390/molecules262166481420-3049https://doaj.org/article/371c3b38b9e44be49d8dc114324e28ce2021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6648https://doaj.org/toc/1420-3049Acute 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[<i>e</i>][1,4]oxazepin-2(3<i>H</i>)-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.Laia Josa-CulleréThomas J. CogswellIrene GeorgiouMorgan Jay-SmithThomas R. JacksonCarole J. R. BatailleStephen G. DaviesParesh VyasThomas A. MilneGraham M. WynneAngela J. RussellMDPI AGarticleacute myeloid leukemiadifferentiationphenotypic screenCD11bbenzooxazepinonesOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6648, p 6648 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	acute myeloid leukemia differentiation phenotypic screen CD11b benzooxazepinones Organic chemistry QD241-441
spellingShingle	acute myeloid leukemia differentiation phenotypic screen CD11b benzooxazepinones Organic chemistry QD241-441 Laia Josa-Culleré 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 Angela J. Russell Identification and Preliminary Structure-Activity Relationship Studies of 1,5-Dihydrobenzo[<i>e</i>][1,4]oxazepin-2(3<i>H</i>)-ones That Induce Differentiation of Acute Myeloid Leukemia Cells In Vitro
description	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[<i>e</i>][1,4]oxazepin-2(3<i>H</i>)-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.
format	article
author	Laia Josa-Culleré 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 Angela J. Russell
author_facet	Laia Josa-Culleré 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 Angela J. Russell
author_sort	Laia Josa-Culleré
title	Identification and Preliminary Structure-Activity Relationship Studies of 1,5-Dihydrobenzo[<i>e</i>][1,4]oxazepin-2(3<i>H</i>)-ones That Induce Differentiation of Acute Myeloid Leukemia Cells In Vitro
title_short	Identification and Preliminary Structure-Activity Relationship Studies of 1,5-Dihydrobenzo[<i>e</i>][1,4]oxazepin-2(3<i>H</i>)-ones That Induce Differentiation of Acute Myeloid Leukemia Cells In Vitro
title_full	Identification and Preliminary Structure-Activity Relationship Studies of 1,5-Dihydrobenzo[<i>e</i>][1,4]oxazepin-2(3<i>H</i>)-ones That Induce Differentiation of Acute Myeloid Leukemia Cells In Vitro
title_fullStr	Identification and Preliminary Structure-Activity Relationship Studies of 1,5-Dihydrobenzo[<i>e</i>][1,4]oxazepin-2(3<i>H</i>)-ones That Induce Differentiation of Acute Myeloid Leukemia Cells In Vitro
title_full_unstemmed	Identification and Preliminary Structure-Activity Relationship Studies of 1,5-Dihydrobenzo[<i>e</i>][1,4]oxazepin-2(3<i>H</i>)-ones That Induce Differentiation of Acute Myeloid Leukemia Cells In Vitro
title_sort	identification and preliminary structure-activity relationship studies of 1,5-dihydrobenzo[<i>e</i>][1,4]oxazepin-2(3<i>h</i>)-ones that induce differentiation of acute myeloid leukemia cells in vitro
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/371c3b38b9e44be49d8dc114324e28ce
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Identification and Preliminary Structure-Activity Relationship Studies of 1,5-Dihydrobenzo[<i>e</i>][1,4]oxazepin-2(3<i>H</i>)-ones That Induce Differentiation of Acute Myeloid Leukemia Cells In Vitro

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