BTYNB (MDK6620) is an inhibitor of the oncofetal mRNA-binding protein IMP1 (IC50 = 5 μM for IMP1 binding to c-Myc mRNA). MDK6620 downregulates β-TrCP1 mRNA and reduces activation of nuclear transcriptional factors-kappa B (NF-κB). It disrupts this enhancer function by impairing IGF2 mRNA-binding protein 1 (IGF2BP1)-RNA association

IMP1 c-Myc mRNA internation:5 μM (IC50)

In cells, BTYNB downregulates several mRNA transcripts regulated by IMP1.?BTYNB destabilizes c-Myc mRNA, resulting in downregulation of c-Myc mRNA and protein.?BTYNB downregulates β-TrCP1 mRNA and reduces activation of nuclear transcriptional factors-kappa B (NF-κB).?The oncogenic translation regulator, eEF2, emerged as a new IMP1 target mRNA, enabling BTYNB to inhibit tumor cell protein synthesis.?BTYNB potently inhibited proliferation of IMP1-containing ovarian cancer and melanoma cells with no effect in IMP1-negative cells.?Overexpression of IMP1 reversed BTYNB inhibition of cell proliferation.?BTYNB completely blocked anchorage-independent growth of melanoma and ovarian cancer cells in colony formation assays.?With its ability to target c-Myc and to inhibit proliferation of difficult-to-target melanomas and ovarian cancer cells, and with its unique mode of action, BTYNB is a promising small molecule for further therapeutic evaluation and mechanistic studies[1].