Identification and Preliminary Structure-Activity Relationship Studies of 1,5-Dihydrobenzo[ e ][1,4]oxazepin-2(3 H )-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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Published in | Molecules (Basel, Switzerland) Vol. 26; no. 21; p. 6648 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Switzerland
MDPI AG
02.11.2021
MDPI |
Subjects | |
Online Access | Get full text |
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Summary: | 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[
][1,4]oxazepin-2(3
)-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. |
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ISSN: | 1420-3049 1420-3049 |
DOI: | 10.3390/molecules26216648 |