Tor1 Activators

The class of chemicals known as Tor1 Activators consists of compounds that primarily act on the PI3K/Akt pathway, the cAMP/PKA pathway, or the intracellular level of essential amino acids or glucose, leading to the indirect activation of Tor1. Tor1 is part of the TORC1 complex that is regulated by these pathways. The first group of activators form part of the PI3K/Akt pathway, which leads to the inhibition of the TSC1/2 complex, a negative regulator of the TOR pathway. This removes the inhibitory effect on Tor1, leading to its activation. Activators of this class also interact with the TOR pathway through the Rag GTPases and AMPK, respectively. They activate the TOR pathway when intracellular levels of amino acids are high, while glucose does so by increasing the cellular energy level, which is sensed directly by AMPK.

Tor1 Activators enhance the cAMP/PKA pathway, causing the PKA-dependent inhibition of the TSC1/2 complex, leading to the activation of Tor1. They also act on acetyltransferase EP300 and Sirt. A small group of activators in this class exert their effects on Tor1 through more unique mechanisms. They inhibit acetyltransferase EP300, leading to the deacetylation of TSC2, a component of the TSC1/2 complex, which negatively regulates the TOR pathway, including Tor1. Laslty, activators of this class also inhibit Sirt1, a positive regulator of TSC2, thus activating the mTOR pathway and Tor1.