What are Torque One inhibitors?

Torque One inhibitors are compounds designed to specifically inhibit the TORC1 (Target of Rapamycin Complex 1) pathway, which is part of the broader mTOR (mammalian Target of Rapamycin) signaling pathway. These inhibitors work by binding to the components of the TORC1 complex and blocking its activity, leading to various cellular effects.

There are two types of Torque One inhibitors: allosteric and catalytic. Allosteric inhibitors bind to a site on the mTOR molecule other than the active site, causing a conformational change that inhibits its activity. Catalytic inhibitors, on the other hand, bind directly to the active site of mTOR, blocking its catalytic function effectively. A combination of these two types can have synergistic effects, making the inhibition more potent and selective for Torque One 1 2.

It has been noted that some drugs, initially designed as dual mTOR/PI3 kinase inhibitors for cancer, are more selective for Torque One at clinically achievable concentrations. For example, RTB 101, at certain doses, selectively inhibits TORC1 without significantly affecting mTORC2, which is beneficial because mTORC2 inhibition can lead to undesirable side effects 3.

Studies have shown that differential inhibition of TORC1 and avoidance of TORC2 inhibition can lead to beneficial outcomes, such as enhanced immune function without the adverse effects often associated with broad-spectrum mTOR inhibitors 4 5.