Small-molecule CSF1R kinase inhibitors; review of patents 2015-present

Area of Science:

• Biochemistry
• Pharmacology
• Oncology

Background:

• Colony stimulating factor 1 receptor (CSF-1R) is a class III receptor tyrosine kinase crucial for myeloid cell development and function.
• CSF-1R signaling influences monocyte, macrophage, dendritic cell, and osteoclast differentiation and survival.
• Dysregulated CSF-1R signaling contributes to tumor progression via tumor-associated macrophages (TAMs).

Purpose of the Study:

• To review the recent advancements in small molecule inhibitors of CSF-1R.
• To highlight the diversity of chemical classes and therapeutic applications of CSF-1R inhibitors.
• To discuss the expanding utility of CSF-1R inhibitors in various disease states.

Main Methods:

• Literature review of journal articles and patent applications from the last 5 years.
• Analysis of recent developments in CSF-1R inhibitor research.
• Focus on potent and selective small molecule inhibitors.

Main Results:

• Significant increase in research activity and patent filings for CSF-1R inhibitors since 2019.
• Discovery of diverse chemical scaffolds demonstrating potent and selective CSF-1R inhibition.
• Identification of pexidartinib's approval for tenosynovial giant cell tumors as a recent milestone.

Conclusions:

• The field of CSF-1R inhibitors has seen rapid development with numerous potent chemotypes emerging.
• CSF-1R inhibitors show promise beyond cancer, including applications in dementia, inflammatory bowel disease, rheumatoid arthritis, and fibrosis.
• Continued research is expanding the therapeutic landscape for CSF-1R targeted therapies.