Definition

An orally bioavailable inhibitor of the serine/threonine kinase p90 ribosomal S6 kinase (p90RSK; RSK) subtypes 1-4, with high selectivity for RSK subtype 2 (RSK2), with potential antineoplastic activity. Upon administration of the RSK1-4 inhibitor PMD-026, this agent targets and inhibits the RSK subtypes, thereby inhibiting RSK-mediated signaling. This prevents the phosphorylation and activation of the transcription factor Y-box binding protein-1 (YB-1) and leads to cell cycle arrest, an induction of apoptosis, and an inhibition of tumor cell proliferation in RSK-expressing tumor cells. RSK is overexpressed in a variety of cancers, especially in triple negative breast cancer (TNBC). It plays a key role in tumor cell proliferation, differentiation, survival, and metastasis.