Mechanistic target of rapamycin kinase messenger RNA (MTOR mRNA) (MTOR mRNA)

Mechanistic target of rapamycin kinase messenger RNA (MTOR mRNA) serves as the essential template for the synthesis of the mTOR protein, a central hub in the PI3K/AKT/mTOR signaling pathway that regulates cell growth, proliferation, and survival [UniProt: P42345]. As a therapeutic target, MTOR mRNA is primarily addressed through the use of antisense oligonucleotides (ASOs) or RNA interference (RNAi) technologies designed to reduce the total cellular pool of mTOR protein [PubMed: 29109230]. This approach is intended to provide more comprehensive inhibition of the pathway compared to traditional ATP-competitive or allosteric kinase inhibitors, which often fail to suppress both mTORC1 and mTORC2 complexes or trigger compensatory feedback loops [Nature Communications: 10.1038/s41467-017-01604-x]. Dysregulation of the mTOR pathway is a critical driver in various malignancies and genetic syndromes such as tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM) [NIH: NBK1116]. Experimental drugs like AZD4785 have demonstrated the feasibility of depleting MTOR mRNA to achieve potent anti-tumor effects in preclinical models [AstraZeneca]. However, the clinical application of MTOR mRNA targeting faces challenges related to systemic metabolic side effects, including hyperglycemia and hyperlipidemia, as well as potential immune-related toxicities [StatPearls: NBK537193]. Additionally, the delivery of these large molecules to target tissues remains a significant hurdle in clinical development.

Other names

Mammalian target of rapamycin mRNAFRAP1 mRNARAFT1 mRNAMTOR transcriptFK506-binding protein 12-rapamycin-associated protein 1 mRNA

Antisense-mediated RNase H-dependent degradation of mRNA