Definition

An orally bioavailable inhibitor of the serine/threonine kinases AKT (protein kinase B), 90S ribosome S6 kinase (p90RSK; RSK) and 70S ribosome S6 kinase (p70S6K; S6K), with potential antineoplastic activity. Upon oral administration, AKT/RSK/S6K inhibitor TAS0612 targets, binds to, and inhibits the activity of AKT, p90RSK and p70S6K. This inhibits both the AKT/mTOR/p70S6K and RAS/RAF/MEK/p90RSK signaling pathways and prevents the phosphorylation, nuclear translocation, and activation of the transcription factor Y-box-binding protein 1 (YBX1; YB-1). This may lead to cell cycle arrest, an induction of apoptosis, and an inhibition of tumor cell proliferation in tumor cells that have overactivated AKT/mTOR/p70S6K and RAS/RAF/MEK/p90RSK signaling pathways. Nuclear expression of YBX1 is associated with drug resistance such as antiestrogen resistance. AKT, RSK and S6K play key roles in tumor cell proliferation, differentiation, survival, and metastasis.