RIV-8

RIV-8 is a first-in-class, potent, and selective small molecule inhibitor of Right Open Reading Frame Kinase 2 (RIOK2), an atypical kinase that plays a critical role in the maturation of the 40S ribosomal subunit. Developed by River 37, a subsidiary of Roivant Sciences, RIV-8 is designed to exploit the dependency of certain cancer cells on accelerated ribosome biogenesis. By binding to the ATP-binding site of RIOK2, RIV-8 prevents the phosphorylation of downstream targets and the release of RIOK2 from the pre-40S particle, leading to a block in protein synthesis and the induction of nucleolar stress. This stress response typically activates p53 and other pro-apoptotic signaling pathways, resulting in the selective elimination of tumor cells. RIV-8 is primarily being investigated for the treatment of hematologic malignancies, such as acute myeloid leukemia (AML), and various solid tumors where RIOK2 is overexpressed.