Rag C Inhibitors

The chemical class termed Rag C Inhibitors consists of compounds that do not inhibit Rag C directly but rather target signaling pathways and cellular processes that Rag C influences. Rag C is a part of the Ragulator-Rag complex that activates mTORC1 in response to amino acid levels, which is essential for cellular growth and metabolism. The indirect inhibition of Rag C is achieved by the modulation of upstream or downstream components of this signaling axis.

Compounds like Metformin and AICAR work by activating AMP-activated protein kinase (AMPK), which is a negative regulator of the mTORC1 complex. By activating AMPK, these compounds lead to the inhibition of mTORC1, thus indirectly suppressing the function of Rag C, which is crucial for the activation of mTORC1 in amino acid signaling. Rapamycin, a well-known inhibitor of the mTOR pathway, forms a complex with FKBP12 and specifically inhibits mTORC1, a key downstream element of the Rag C pathway. This inhibition results in a decrease in the functional output of Rag C. Other chemicals such as Torin 1, KU-0063794, WYE-687, and MLN0128 (Sapanisertib) inhibit both mTORC1 and mTORC2 complexes. Since Rag C is specifically involved in mTORC1 activation, the inhibition of this complex leads to a reduction in Rag C-mediated signaling. Dual inhibitors like PI-103, PF-04691502, and AZD8055 target both phosphatidylinositol 3-kinase (PI3K) and mTOR, enzymes that are key regulators of cell growth and proliferation upstream of Rag C. By inhibiting these kinases, these compounds indirectly suppress the activation of Rag C and its subsequent signaling processes. Palomid 529 is another agent that modulates the mTOR/AKT pathway, and by doing so, it indirectly diminishes Rag C activity.