blz-945 and Neoplasms

Tumor-associated macrophages (TAMs) have a significant presence in the tumor stroma across multiple human malignancies and are believed to be beneficial to tumor growth. Targeting CSF1R has been proposed as a potential therapy to reduce TAMs, especially the protumor, immune-suppressive M2 TAMs. Additionally, the high expression of CSF1R on tumor cells has been associated with poor survival in certain cancers, suggesting tumor dependency and therefore a potential therapeutic target. The CSF1-CSF1R signaling pathway modulates the production, differentiation, and function of TAMs; however, the discovery of selective CSF1R inhibitors devoid of type III kinase activity has proven to be challenging. We discovered a potent, highly selective, and orally bioavailable CSF1R inhibitor, IACS-9439 (

Topics: Antineoplastic Agents; Benzothiazoles; Drug Stability; Humans; Microsomes, Liver; Molecular Structure; Neoplasms; Pyrimidines; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; Structure-Activity Relationship; THP-1 Cells; Tumor-Associated Macrophages