IHMT-CSF1R-833 was found to be a potent and selective CSF1R inhibitor

Recently, Professor Liu Qingsong's team at Hefei Institute of Physical Sciences, Chinese Academy of Sciences discovered a highly effective selective colony-stimulating factor 1 receptor kinase inhibitor IHMT-CSF1R-833.

Colony-stimulating factor 1 receptors (CSF1R) belong to the type III growth factor receptor family
.
The CSF1R signaling pathway is essential for macrophage differentiation and survival, and plays an indispensable role
in the tumor-related macrophages in tumor-promoting and immunosuppressive functions.
Inhibiting tumor-associated macrophage survival/activation by inhibiting the CSF1R signaling pathway has become an attractive cancer immunotherapy strategy
.

Most current CSF1R inhibitors lack proper selectivity for other kinases, making it difficult to correlate
their therapeutic effects with CSF1R inhibition.
Therefore, identifying different chemical scaffold CSF1R inhibitors is necessary
for both preclinical mechanism and clinicopathological studies.

In this study, the researchers reported a potent and selective CSF1R inhibitor, IHMT-CSF1R-833, using a computer-aided drug design-guided centralized medicinal chemistry approach
.

IHMT-CSF1R-833 has strong inhibitory activity against CSF1R with IC50 value of 5.
14 nM, which inhibits phosphorylation of CSF1R and its downstream signaling pathway in a dose-dependent manner
.

At the same time, it has high selectivity
for a wide range of human kinases.
In addition, IHMT-CSF1R-833 repolarizes M2 macrophages to M1 macrophages in RAW264.
7 macrophages in a dose-dependent manner
.

In vivo, IHMT-CSF1R-833 demonstrated acceptable oral pharmacokinetic properties in rats and dose-dependent antitumor effects
in the M-NFS-60 tumor transplant tumor model.

These results suggest that IHMT-CSF1R-833 may be a valuable research tool
for CSF1R-mediated macrophages in preclinical mechanisms and clinicopathological studies.