What can inhibit Glutamine?
FROM CHAT GPT: Glutamine inhibition is often targeted in cancer therapy or metabolic research to restrict glutamine's role in cellular processes, especially since many tumors are glutamine-dependent. Here are some common approaches and compounds used for glutamine inhibition: 1. Glutaminase (GLS) Inhibitors: Glutaminase is an enzyme that converts glutamine into glutamate, a key step in glutamine metabolism. Inhibiting glutaminase can reduce glutamine availability for cell growth, especially in cancer cells. - CB-839 (Telaglenastat): One of the most well-known glutaminase inhibitors used in clinical trials for cancer therapy. - BPTES: An early inhibitor of GLS, although less potent than CB-839. 2. Glutamine Analogues: These are structural analogs of glutamine that can compete with glutamine for uptake and utilization in cells. - DON (6-Diazo-5-oxo-L-norleucine): A classic glutamine analog that inhibits multiple enzymes involved in glutamine metabolism. - Azaserine: Another glutamine analog that inhibits enzymes utilizing glutamine, particularly in nucleotide synthesis. 3. ASCT2 (SLC1A5) Inhibitors: ASCT2 is a glutamine transporter that facilitates the uptake of glutamine into cells. Blocking this transporter can limit glutamine's availability inside the cell. - V-9302: A small-molecule inhibitor targeting ASCT2, reducing glutamine uptake. 4. mTOR Inhibitors: Since glutamine can activate the mTOR pathway, which is crucial for cell growth and proliferation, mTOR inhibitors can indirectly affect glutamine metabolism. - Rapamycin (Sirolimus): An mTOR inhibitor that can be used to suppress the glutamine-driven mTOR signaling cascade. 5. GLUD (Glutamate Dehydrogenase) Inhibitors: GLUD converts glutamate (derived from glutamine) into α-ketoglutarate for use in the tricarboxylic acid (TCA) cycle. Inhibiting GLUD can reduce the energy and biosynthetic precursors provided by glutamine metabolism. 6. Inhibition of Amino Acid Synthesis Pathways: