mTORC1 signalling is vital in many cellular processes like cell proliferation. Defects in mTORC1 signalling systems can cause negative implications on aging, chronic diseases, cancers & other diseases. The G-protein Rheb (in grey) with GTP (red) is a master regulator that assists the activation of mTORC1. Through mutation studies, it was found that the Rheb binds with mTORC1 through the Switch II region. The molecule NR1 (in yellow) is a drug that inhibits mTORC1 signalling through blocking and decreasing the affinity of mTORC1 binding to Rheb, thus interfering with mTORC1 signalling. The IC50 (potency) of NR1 is 2.1 μM. Other proposed drugs that inhibited mTORC1 activation, like rapamycin, caused adverse effects from inhibiting mTORC2 signalling as well. However, NR1 is a unique & selective inhibitor of mTORC1 activation, irrespective to the duration of treatment.
Dalbey, R., et al. 2007. The Enzymes.Vol 25
Mahoney, S.J., et al. 2018 A small molecule inhibitor of Rheb selectively targets mTORC signalling.
Comments