Rheb + NR1

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mTORC1 signalling affects numerous cellular activities such as protein synthesis and degradation, nucleotide production, cell growth, and autophagy. Aberrant mTORC1 signalling, however, contributes to neurodegenerative disorders, cancers, and other health issues. Consequently, there is a need for selective mTORC1 inhibition that can be used to treat chronic diseases without the negative consequences of downregulating or inhibiting mTORC2. Signalling of mTOR1 is controlled by the heterotrimeric TSC complex. When this complex is disrupted, the following sequence occurs: TSC1/TSC2 (GAP) becomes inactivated due to phosphorylation on specific amino acids –> GAP can no longer hydrolyze GTP on Rheb's G protein –> Rheb-GTP then activates mTORC1. Rheb binds with mTORC1 in the Switch II region, activating mTORC1. Given Rheb's selective role in mTORC1, which has no direct impact on mTORC2, targeting Rheb with a suitable molecular inhibitor, NR1, presents a viable option for blocking activity and treating chronic diseases.