Notably, MSU-42011 and selumetinib alone similarly inhibited CCL2 mRNA expression by 25% in THP1 macrophages stimulated with CM from PNF cells, and the inhibition of CCL2 mRNA expression was enhanced to 50% with combination treatment. Taken together, our data suggest that MSU-42011 should be tested in relevant preclinical models of NF1.

almost 2 years ago

Combination therapy

KRAS (KRAS proto-oncogene GTPase) • NF1 (Neurofibromin 1) • CCL2 (Chemokine (C-C motif) ligand 2) • GLI2 (GLI Family Zinc Finger 2) • MRC1 (Mannose Receptor C-Type 1) • PERK (Pancreatic EIF2-Alpha Kinase)

NF1 mutation

Koselugo (selumetinib) • MSU-42011

almost2years

Activation of the RXR nuclear receptor regulates CD4 T cell activity in a murine model of HER2+ breast cancer (AACR 2023)

In conclusion, MSU42011 increased recruitment and activation of CD4 T cells in vitro and in HER2+ mammary tumors. These data, in combination with our previous work showing that RXR agonists reduce expression of tumor-promoting FOXP3 T cells in vitro and in vivo, confirm a strong correlation between RXR pharmacologic activation and CD4 T cell activation within the tumor microenvironment.

almost 2 years ago

Preclinical • PD(L)-1 Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • ITGAM (Integrin, alpha M) • FOXP3 (Forkhead Box P3) • ITGAX (Integrin Subunit Alpha X)

PD-L1 expression • FOXP3 expression

MSU-42011