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
| Autor: | Thomas R. Jackson, Graham Michael Wynne, Thomas J. Cogswell, Laia Josa-Culleré, Morgan Jay-Smith, Angela J. Russell, Carole J. R. Bataille, Irene Georgiou, Paresh Vyas, Stephen G. Davies, Thomas A. Milne |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Phenotypic screening
Pharmaceutical Science Antineoplastic Agents Chemistry Techniques Synthetic acute myeloid leukemia Article Analytical Chemistry Structure-Activity Relationship QD241-441 Pharmacokinetics Cell Line Tumor Drug Discovery Humans Structure–activity relationship Physical and Theoretical Chemistry Cells Cultured benzooxazepinones differentiation phenotypic screen CD11b Dose-Response Relationship Drug Molecular Structure biology Organic Chemistry Myeloid leukemia Cell Differentiation Small molecule In vitro Leukemia Myeloid Acute Integrin alpha M Chemistry (miscellaneous) Cell culture biology.protein Cancer research Molecular Medicine Drug Screening Assays Antitumor |
| Zdroj: | Molecules; Volume 26; Issue 21; Pages: 6648 Molecules, Vol 26, Iss 6648, p 6648 (2021) Molecules |
| DOI: | 10.3390/molecules26216648 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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