SHMT1 Inhibitor

SHMT2-IN-1 is a potent serine hydroxymethyltransferase 2 (SHMT2) inhibitor with an IC₅₀ of 1.21 μM and a K_D of 10.6 μM. SHMT2-IN-1 binds to the folate binding site of SHMT2. SHMT2-IN-1 also inhibits SHMT1 with an IC₅₀ of 1.83 μM. SHMT2-IN-1 can inhibit cancer cells proliferation, migration and invasion. SHMT2-IN-1 can induce cells apoptosis and ROS production and cause G2/M phase arrest. SHMT2-IN-1 can be used for the research of cancer, such as esophageal cancer.

SHMT-IN-3 (Hit 1) is a SHMT1 and SHMT2 inhibitor with an IC50 of 0.53 µM for human SHMT1. SHMT-IN-3 exhibits noncompetitive inhibition against serine.

AGF347 is a potent and multi-targeted antifolate that targets serine hydroxymethyltransferase (SHMT)2 in the mitochondria and SHMT1 in the cytosol, and inhibits de novo purine biosynthesis. AGF347 induces apoptosis, inhibits mTOR signaling, decreases GSH pools, and increases ROS. AGF347 inhibits proliferation of Cisplatin (HY-17394) sensitive and resistant epithelial ovarian cancer (EOC) cells. AGF347 exhibits antitumor efficacy in SKOV3 EOC xenograft mouse models. AGF347 can be used for ovarian cancer research.