2. Signaling Pathways
  3. Metabolic Enzyme/Protease
  4. SHMT
  5. SHMT1 Isoform

SHMT1

SHMT1 (serine hydroxymethyltransferase 1) is the cytosolic isoform of serine hydroxymethyltransferase and a pyridoxal phosphate-dependent enzyme that catalyzes the reversible conversion of serine and tetrahydrofolate into glycine and 5,10-methylenetetrahydrofolate, thereby supplying one-carbon units required for thymidylate, purine, and methionine biosynthesis within cellular folate metabolism[1][2]. Mechanistically, SHMT1 functions as a central component of cytosolic one-carbon metabolism, linking serine-glycine interconversion to nucleotide production and supporting cellular proliferation through regulation of folate-dependent biosynthetic pathways[3][4]. In disease-associated settings, altered dependence on cytosolic one-carbon flux has been linked to tumor growth, and experimental suppression of SHMT1 impairs pyrimidine biosynthesis and reduces tumor growth in vivo in models characterized by limited intracellular folate retention[3]. Compared with the mitochondrial isoform SHMT2, which primarily supports mitochondrial one-carbon metabolism and is frequently upregulated in proliferating and malignant tissues, SHMT1 predominantly operates in the cytosolic compartment and contributes to distinct metabolic requirements of folate-mediated biosynthesis[4][5]. Functional overlap between SHMT isoforms has been reported in thymidylate biosynthesis, yet their subcellular localization and metabolic context remain different, emphasizing the importance of isoform-specific investigation in experimental systems[6]. For research applications, SHMT has emerged as a pharmacological target in one-carbon metabolism, and small-molecule inhibitors such as (+)-SHIN-1 have been developed to inhibit human SHMT activity, providing useful tools for mechanistic studies of folate-dependent metabolism and cancer-associated metabolic reprogramming[7][8].

SHMT1 Related Products (3):

Cat. No. Product Name Effect Purity
  • HY-178432
    SHMT2-IN-1
    		Inhibitor
    SHMT2-IN-1 is a potent serine hydroxymethyltransferase 2 (SHMT2) inhibitor with an IC50 of 1.21 μM and a KD 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.
  • HY-148545
    SHMT-IN-3
    		Inhibitor ≥98.0%
    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.
  • HY-177092
    AGF347
    		Inhibitor
    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.