MO-2097 is an inhibitor of RAF-1 and HIF-1α. It destabilizes RAF-1, reducing EMT-related transcription factors and mesenchymal markers. MO-2097 suppresses HIF-1α protein expression under hypoxic or hypoxia-mimicking conditions via hnRNPA2B1. It induces mitochondrial ROS production, leading to cell apoptosis. By inhibiting the RAF/MEK/ERK signaling pathway, MO-2097 effectively prevents colorectal cancer metastasis. It also inhibits tumor growth in human colorectal cancer HCT116 cell xenograft mouse models. MO-2097 is applicable for colorectal cancer research.

MO-2097 exhibits several biological activities: at concentrations of 10-30 μM for 24-48 hours, it inhibits DLD-1 and HCT116 cell migration; at 10-50 μM for 1-6 hours, it suppresses the RAF-1 driven RAF/MEK/ERK signaling cascade in the same cell lines. At 10-30 μM over 5-9 days, MO-2097 inhibits the invasiveness of colorectal cancer cells (DLD-1 and HCT116) in 3D tumor spheroid models. Additionally, at concentrations of 30-100 μM for 4 hours, it prevents angiogenesis by inhibiting tubular formation in HUVEC cells. MO-2097 demonstrates low toxicity in HeLa CCL2 and HCT116 cells at 25-500 μM over 24 hours, binding directly to hnRNPA2B1 and reducing HIF-1α expression. At 25-50 μM for 24 hours under hypoxic conditions, it reduces the expression of HIF-1α target genes mRNA (HK1, MRP1, SLC1A5, IL-6, and VEGF) in HeLa CCL2 and HCT116 cells. In HeLa CCL2 cells, MO-2097 induces mitochondrial ROS production at 12.5-50 μM over 24 hours, leading to apoptosis, indicated by the cleavage of caspase 3 and caspase 9. Finally, at 12.5-50 μM for 7-10 days, MO-2097 induces specific anticancer effects in the hypoxic regions of 3D cultured spheroid models and human colon cancer organoids.

MO-2097, administered at 25-50 mg/kg via intraperitoneal injection every other day for 15 days, suppresses tumor growth in an HCT116 cell xenograft mouse model by inducing apoptosis through inhibition of HIF-1α expression.