Definition

A bi-steric inhibitor of the raptor-mammalian target of rapamycin (mTOR) complex 1 (mTOR complex 1; mTORC1), with potential antineoplastic activity. Upon administration, mTORC1 kinase inhibitor RMC-5552 selectively targets, binds to and inhibits the serine/threonine kinase activity of mTORC1, resulting in decreased expression of mRNAs necessary for cell cycle progression, which may induce cell cycle arrest and tumor cell apoptosis. mTORC1 phosphorylates transcription factors, such as ribosomal protein S6 kinase beta-1 (S6K1) and eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), which stimulate protein synthesis and regulate cell growth, proliferation, motility, and survival. RMC-5552 is able to suppress the phosphorylation of the tumor suppressor activity of 4EBP1, induces apoptosis and decreases proliferation of mTORC1-expressing tumor cells. mTORC1 is a serine/threonine kinase that is upregulated in certain tumor cell types. It plays an important role in the PI3K/Akt/mTOR signaling pathway, which is often deregulated in cancer cells and promotes cell growth, survival, and resistance to chemotherapy and radiotherapy. Selective mTORC1 inhibition improves the poor clinical tolerability as compared to agents that also cause inhibition of the mTORC2 complex.