GW-2580

More importantly, we found that Proguanil's inhibitory effect on U87MG cell growth and migration was positively correlated with CSF1R expression, and this effect diminished following CSF1R knockdown and Proguanil demonstrated synergistic effects with CSF1R-targeting positive drugs (BLZ945 and GW2580). Meanwhile, Proguanil targeted CSF1R to inhibit M2-type polarization of tumor-associated macrophages (TAMs) and their proliferation, thus altering the tumor microenvironment while indirectly suppressing the proliferation and migration of U87MG cells. Taken together, these findings suggest that Proguanil may serve as a promising CSF1R antagonist for GBM treatment.

This comparative analysis of CSF1R-targeting drugs on patient-derived GAMs and human glioblastoma avatars identified GW2580 as the most powerful inhibitor with the ability to polarize immunosuppressive GAMs to a proinflammatory phenotype, supporting antitumor T cell responses while also exerting a direct antitumor effect. These data indicate that GW2580 could be an important pillar in future therapies for glioblastoma.

These findings show that peripheral respiratory viral infection with IAV is capable of altering OL homeostasis and indicate that microglia activation is likely involved in the process.

Tumours coopt intratumoural HSPC fate determination via CSF-1 signaling to overcome the effects of RT. Thus, limiting intratumoural HSPC activity represents an attractive strategy for improving the clinical treatment of solid tumours.

In summary, we showed that CSF-1R blockade with the SMI GW2580 can reprogram GAM phenotype and thereby improve T cell activation. This strongly suggests further studies on the use of GW2580 in combination with immunotherapeutic approaches for the treatment of GBM.

GW2580, a CSF1-receptor inhibitor was tested in-vitro as well as in-vivo, singularly and in combination with S-nitrosoglutathione (GSNO), an active NO donor. In-vivo dosage of 40mg/kg/day for GW2580 and 10mg/kg/day for GSNO were used... Our findings demonstrated a direct role of increased NO-based immunotherapy to augment the action of CSF1R inhibition to suppress the macrophage polarization in in-vivo models for castration resistant prostate cancer.

Administration of the c-FMS/CSF1R kinase inhibitors GW2580 and BLZ945 significantly reduced human LC migration. We also detected presence of transcripts for its ligand, CSF1, but not IL34, in all tested LCH cases. CSF1R and CSF-1 expression in LCH, and their role in LC migration and differentiation, suggests CSF1R signaling blockade as a candidate rational approach for treatment of LCH, including the BRAFV600E and wild-type forms of the disease.