Discovery of potent colony-stimulating factor 1 receptor inhibitors by replacement of hinge-binder moieties
- Authors
- Lee, J.W.; Park, J.; Kim, J.; Kim, J.; Choi, C.; Min, K.H.
- Issue Date
- 15-Apr-2021
- Publisher
- Elsevier Masson s.r.l.
- Keywords
- CSF1R; Hinge binder; Kinase inhibitor
- Citation
- European Journal of Medicinal Chemistry, v.216
- Journal Title
- European Journal of Medicinal Chemistry
- Volume
- 216
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/47537
- DOI
- 10.1016/j.ejmech.2021.113298
- ISSN
- 0223-5234
1768-3254
- Abstract
- Tumor-associated macrophages (TAMs) are predominantly associated with tumor growth. Colony-stimulating factor 1 receptor (CSF1R) acts as a key regulator of TAM survival and differentiation and is a molecular target for cancer therapies. Herein, novel CSF1R inhibitors were identified through a replacement strategy for the hinge-binding moiety. The introduction of imidazo[1,2-a]pyridine (49) or pyrazolo[1,5-a]pyridine (50) as hinge binders led to 87% and 82% inhibition at 10 nM for CSF1R in the enzymatic assay, with IC50 values of 25 nM and 27 nM in MNFS60 cells, respectively. These derivatives significantly inhibited CSF1R phosphorylation in cells. Our approach could be utilized as a strategy to discover novel kinase inhibitors. © 2021 Elsevier Masson SAS
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Pharmacy > School of Pharmacy > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/47537)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.