mSHMT Inhibitors

The inhibitors listed here target various aspects of folate and one-carbon metabolism, which are closely related to the function of mSHMT in mitochondria.Methotrexate, Pemetrexed, Aminopterin, and similar compounds inhibit enzymes in folate metabolism, such as dihydrofolate reductase and thymidylate synthase. By doing so, they can indirectly influence the availability of substrates or cofactors necessary for mSHMT's activity. 5-Fluorouracil (5-FU) and Raltitrexed are known to inhibit thymidylate synthase, an enzyme involved in the synthesis of thymidine, a nucleoside necessary for DNA synthesis. This inhibition can affect the folate cycle and potentially the role of mSHMT.

Trimethoprim, Pyrimethamine, and Sulfonamides are more commonly known for their antibacterial properties, but their mechanism of action, which involves inhibition of folate synthesis, could have implications for human enzymes in the folate pathway, indirectly affecting mSHMT. LY345899 is a broad inhibitor of folate-dependent enzymes, potentially altering the balance of folate metabolism and impacting mSHMT function. AG-221 (Enasidenib) and glutaminase inhibitors like CB-839 (Telaglenastat) and BPTES affect cellular metabolism pathways that intersect with one-carbon metabolism, potentially influencing mSHMT activity indirectly.