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Identification and Development of 1,4-Diaryl-1,2,3-triazolo-Based Ureas as Novel FLT3 Inhibitors.
- Source :
-
ACS medicinal chemistry letters [ACS Med Chem Lett] 2020 Jul 27; Vol. 11 (8), pp. 1567-1572. Date of Electronic Publication: 2020 Jul 27 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- A class of 1,4-diaryl-1,2,3-triazolo-based ureas were synthesized and developed as novel FLT3 inhibitors. The representative compound 28 strongly inhibited FLT3-ITD kinase (IC <subscript>50</subscript> = 32.8 nM) and isogenic BaF3-FLT3-ITD cell (GI <subscript>50</subscript> = 0.6 nM). It exhibited potent inhibition against FLT3-ITD positive MV4-11 (GI <subscript>50</subscript> = 3.0 nM) and MOLM-13 (GI <subscript>50</subscript> = 5.9 nM) cell lines and high selectivity over FLT3-WT cell lines. It also displayed good pharmacokinetics properties and demonstrated promising oral in vivo efficacy in a MV4-11 cell xenografted mouse model. It might be a potent lead compound for further development to treat FLT3-ITD driven acute myloid leukemia.<br />Competing Interests: The authors declare no competing financial interest.<br /> (Copyright © 2020 American Chemical Society.)
Details
- Language :
- English
- ISSN :
- 1948-5875
- Volume :
- 11
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- ACS medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 32832025
- Full Text :
- https://doi.org/10.1021/acsmedchemlett.0c00216