Rapamycin-insensitive companion of mammalian target of rapamycin (RICTOR) (RICTOR)

Rapamycin-insensitive companion of mammalian target of rapamycin (RICTOR) is a vital structural component of the mTORC2 complex, distinguishing it from the rapamycin-sensitive mTORC1 (UniProt Q6R327). RICTOR functions as a scaffold that enables mTORC2 to phosphorylate AGC family kinases, most notably Akt at Ser473, which is essential for cell survival and metabolic regulation (Sarbassov et al., 2004, Science). In many cancers, such as small cell lung cancer and breast cancer, RICTOR is frequently amplified or overexpressed, driving oncogenic signaling and contributing to drug resistance (PubMed 31515461). Because RICTOR lacks a traditional catalytic domain, it is considered a non-druggable target by small molecules, leading to the development of mRNA-targeting strategies. Antisense oligonucleotides (ASOs), such as IONIS-827359, are designed to bind and degrade RICTOR mRNA, thereby preventing the formation of the mTORC2 complex and inhibiting tumor growth (Ionis Pharmaceuticals). This approach provides a highly specific method for modulating the mTOR pathway while avoiding the off-target effects associated with broad-spectrum kinase inhibitors.

Other names

RICTORAVO3hAVO3PIAKIAA1999

Antisense oligonucleotide-mediated degradation of RICTOR mRNA, leading to the inhibition of mTORC2 complex assembly and downstream signaling.