MSU-42011 / Akeila Bio, Michigan State University - LARVOL DELTA

The RXR Agonist MSU-42011 Reduces Tumor Burden in a Murine Preclinical NF1-Deficient Model. (PubMed, Cancers (Basel)) - "While selumetinib is FDA-approved for PNFs, its efficacy in MPNSTs is limited and associated with dose-limiting toxicities. These findings suggest RXR agonists may have therapeutic potential against NF1, and their combination with MEK inhibitors could represent a promising strategy for NF1-associated tumors. Further studies are needed to validate these results and assess their translational relevance."

Journal • Preclinical • Brain Cancer • Genetic Disorders • Neurofibromatosis • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor • CD8 • GLI2 • KRAS • NF1

The RXR Agonist MSU-42011 Reduces Tumor Burden in a Murine Preclinical NF1-Deficient Model (Multidisciplinary Digital Publishing Institute) - "In vivo, the combination of MSU-42011 and selumetinib significantly reduced tumor growth, pERK levels, and tumor-promoting macrophages and increased activated CD8+ T cells in syngeneic MPNST models. In NF1-deficient cells, MSU-42011 or selumetinib reduced pERK levels, with combination treatment achieving greater reductions."

Preclinical • Neurofibromatosis • Oncology

The RXR agonist MSU-42011 and the MEK inhibitor selumetinib reduce tumor burden by decreasing pERK levels and modulating immune cell populations within the NF1 tumor microenvironment (AACR 2025) - "The combination of MSU42011 and selumetinib also significantly reduced tumor growth and reduced pERK levels and tumor-promoting CD206+ macrophages in both a LL2 model of lung cancer driven by an activating Kras mutation and a syngeneic mouse model of MPNST. Based on the similarities in RAS activation and immune cell infiltration in NF1 and lung cancer, our next step is to confirm the immunomodulatory and anti-tumor effects of MSU-42011 and selumetinib in a genetically engineered model of PNF and MPNST."

Biomarker • Clinical • Immune cell • Tumor microenvironment • Brain Cancer • Lung Cancer • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor • CCL2 • GLI2 • IL6 • KRAS • MRC1 • NF1 • PERK • TNFA

The RXR agonist MSU-42011 and the MEK inhibitor selumetinib reduce pERK levels in NF1-deficient cells and inhibit cytokine production in macrophages (AACR 2024) - "The combination of MSU42011 and selumetinib also significantly reduced tumor burden in a LL2 model of lung cancer driven by an activating Kras mutation. Based on the similarities in RAS activation and immune cell infiltration in NF1 and lung cancer, our next step is to confirm the immunomodulatory and anti-tumor effects of MSU-42011 and selumetinib in a syngeneic model of PNF and MPNST."

Brain Cancer • Lung Cancer • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor • CCL2 • GLI2 • IL6 • KRAS • MRC1 • NF1 • PERK • TNFA

The retinoid X receptor agonist MSU42011 enhances efficacy of anti-PD1 therapy in a HER2+ breast cancer model through a CD4-IL12 axis (AACR 2024) - "When anti-PD1 antibodies were given at a lower loading dose (200ug and then 100ug twice weekly) followed by a higher dose of MSU42011 (300 mg/Kg of diet), survival markedly increased (p=0.052). These findings demonstrate that activation of RXR in the stroma can be used to increase the effectiveness of immunotherapy."

Clinical • Preclinical • Breast Cancer • HER2 Breast Cancer • Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • HER-2 • IL12A • KRAS

MSU-42011, alone and in combination with selumetinib, reduces pERK levels in NF1 cancer cells and decreases CCL2 expression in THP-1 macrophages (AACR 2023) - "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."

Combination therapy • Brain Cancer • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor • CCL2 • GLI2 • KRAS • MRC1 • NF1 • PERK

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."

IO biomarker • Preclinical • Breast Cancer • HER2 Breast Cancer • Lung Cancer • Oncology • Solid Tumor • CD4 • CD8 • FOXP3 • HER-2 • IL12A • ITGAM • ITGAX • KRAS • PD-L1