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...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | article |
| Language: | EN |
| Published: |
MDPI AG
2021
|
| Subjects: | |
| Online Access: | https://doaj.org/article/371c3b38b9e44be49d8dc114324e28ce |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| 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[<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. |
|---|