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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
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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588310/ https://www.ncbi.nlm.nih.gov/pubmed/34771052 http://dx.doi.org/10.3390/molecules26216648 |
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author | Josa-Culleré, Laia Cogswell, Thomas J. Georgiou, Irene Jay-Smith, Morgan Jackson, Thomas R. Bataille, Carole J. R. Davies, Stephen G. Vyas, Paresh Milne, Thomas A. Wynne, Graham M. Russell, Angela J. |
author_facet | Josa-Culleré, Laia Cogswell, Thomas J. Georgiou, Irene Jay-Smith, Morgan Jackson, Thomas R. Bataille, Carole J. R. Davies, Stephen G. Vyas, Paresh Milne, Thomas A. Wynne, Graham M. Russell, Angela J. |
author_sort | Josa-Culleré, Laia |
collection | PubMed |
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[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. |
format | Online Article Text |
id | pubmed-8588310 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85883102021-11-13 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 Josa-Culleré, Laia Cogswell, Thomas J. Georgiou, Irene Jay-Smith, Morgan Jackson, Thomas R. Bataille, Carole J. R. Davies, Stephen G. Vyas, Paresh Milne, Thomas A. Wynne, Graham M. Russell, Angela J. Molecules Article 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. MDPI 2021-11-02 /pmc/articles/PMC8588310/ /pubmed/34771052 http://dx.doi.org/10.3390/molecules26216648 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Josa-Culleré, Laia Cogswell, Thomas J. Georgiou, Irene Jay-Smith, Morgan Jackson, Thomas R. Bataille, Carole J. R. Davies, Stephen G. Vyas, Paresh Milne, Thomas A. Wynne, Graham M. Russell, Angela 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588310/ https://www.ncbi.nlm.nih.gov/pubmed/34771052 http://dx.doi.org/10.3390/molecules26216648 |
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