Pexidartinib | CSF1R inhibitor

Pexidartinib (1029044-16-3) is a potent and selective dual inhibitor of CSF1R (IC₅₀ = 20nM) and c-KIT (IC₅₀ = 10nM).¹ Inhibition of CSF1R with Pexidartinib resulted in a reprogrammed immune microenvironment that fosters antitumor immunity in a CD8⁺ T-cell-dependent manner in a breast cancer model.¹ CSF1R recruits tumor-infiltrating myeloid cell that suppress tumor immunity – Pexidartinib increased the efficacy of adoptive cell immunotherapy (ACT) in a mouse melanoma model by inhibiting the intratumoral accumulation of immunosuppressive macrophages.^2,3 It has also been shown to increase the efficacy of anti-PD-1^4,5 and DC immunotherapy ⁶.

References/Citations:

1) DeNardo et al. (2011) Leukocyte Complexity Predicts Breast Cancer Survival and Functionally Regulates Response to Chemotherapy; Cancer Discov. 1 54
2) Mok et al. (2014) Inhibition of CSF-1 receptor improves the antitumor efficacy of adoptive cell transfer immunotherapy; Cancer Res.74 15
3)Sluijter et al. (2014) Inhibition of CSF-1R supports T-cell mediated melanoma therapy; PLoS One 9 e104230
4) Peranzoni et al. (2018) Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti-PD-1 treatment; Proc. Natl. Acad. Sci. USA 115 E4041
5) Shi et al. (2019) Modulating the Tumor Microenvironment via Oncolytic Viruses and CSF-1R Inhibition Synergistically Enhances Anti-PD-1 Immunotherapy; Mol. Ther. 27 244
6) Dammeijer et al. (2017) Depletion pf Tumor-Associated Macrophages with a CSF-1R Kinase Inhibitor Enhances Antitumor Immunity and Survival Induced by DC Immunotherapy; Cancer Immunol. Res. 5 535