2. Signaling Pathways
  3. Metabolic Enzyme/Protease
  4. Methylenetetrahydrofolate Dehydrogenase (MTHFD)

Methylenetetrahydrofolate Dehydrogenase (MTHFD)

Methylenetetrahydrofolate dehydrogenase (MTHFD) is a key enzyme in the folate-dependent one carbon metabolism, which is important for the biosynthesis of several amino acids like glycine, alanine and serine, as well as nucleotide bases, formylated methionine and some pro-vitamins. In some bacteria like E. coli, MTHFD (called FolD in this species) is a dual function enzyme that catalyzes the conversion of 5,10-methylenetetrahydrofolate and NADP+ to 5,10-methenyltetrahydrofolate and NADPH (dehydrogenase function), and further converts the first product to 10-formyltetrahdrofolate (cyclohydrolase function). Some microorganisms have a separate enzyme for catalyzing the second cyclohydrolase function (FchA), and some species have an alternative pathway for 10-formyltetrahdrofolate production using formyltetrahydrofolate synthetase (Fhs). In eukaryotes, MTHFD is an important anticancer therapy target.

Methylenetetrahydrofolate Dehydrogenase (MTHFD) Related Products (18):

Cat. No. Product Name Effect Purity Chemical Structure
  • HY-130251
    DS18561882
    		99.87%
    DS18561882 is a highly potent, isozyme-selective methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) inhibitor with an IC50 value of 0.0063 μM. DS18561882 also has inhibitory effect on MTHFD1 (IC50=0.57 μM). DS18561882 exhibits a good oral pharmacokinetic profile.
    DS18561882
  • HY-101943
    LY 345899
    		98.0%
    LY 345899 is a Folate analog and is a methylene tetrahydrofolate dehydrogenase (MTHFD1; DC301) and MTHFD2 inbhibitor with IC50 values of 96 nM and 663 nM, respectively and a Ki of 18 nM for MTHFD1.
    LY 345899
  • HY-155950
    TH9619
    		Inhibitor 99.33%
    TH9619 is a potent inhibitor of dehydrogenase and cyclohydrolase activities in both MTHFD1 and MTHFD2 with a IC50 value of 47 nM, and selectively kills cancer cells. TH9619 induces apoptosis by blocking the S phase. TH9619 has antitumor activity.
    TH9619
  • HY-131943
    DS44960156
    		Inhibitor ≥99.0%
    DS44960156 is a selective MTHFD2 inhibitor with moderate to low blood-brain barrier penetration (IC50=1.6 μM, Ki=1.23 μM). DS44960156 specifically binds to the active site of MTHFD2, disrupts redox homeostasis and blocks serine-mediated one-carbon metabolism, thereby increasing the NAD+/NADH ratio and ROS levels. DS44960156 not only effectively inhibits the proliferation of glioma cells, but also enhances the sensitivity of cells to glutamine starvation-induced death. DS44960156 binds to plasma proteins, shows no mutagenicity, carcinogenicity or acute oral toxicity, and serves as a research agent for glioblastoma multiforme and other cancers.
    DS44960156
  • HY-155219
    TH9028
    		Inhibitor
    TH9028 is an inhibitor of MTHFD2 (IC50 = 11 nM) with IC50 values against hMTHFD2, MTHFD2L, and MTHFD1 being 7.97 nM, 27 nM, and 0.5 nM, respectively. TH9028 also exhibits anti-cancer cell proliferation activity.
    TH9028
  • HY-182355
    MTHFD2-IN-7
    		Inhibitor
    MTHFD2-IN-7 is an orally active, selective MTHFD2 inhibitor with IC50 values of 0.038 μM and 7.44 μM against human hMTHFD1 and hMTHFD2, respectively. MTHFD2-IN-7 exerts its function by binding to the substrate-binding site of MTHFD2 and maintaining interactions with NAD+. Verified by TSA and DARTS assays, MTHFD2-IN-7 not only binds effectively to the target protein, but also possesses Caco-2 permeability and liver microsomal metabolic stability. MTHFD2-IN-7 exhibits favorable pharmacokinetic properties in mice. MTHFD2-IN-7 also significantly inhibits cancer cell proliferation and reduces tumor volume, and serves as a promising small-molecule tool for acute myeloid leukemia research.
    MTHFD2-IN-7
  • HY-183364
    MTHFD2-IN-8
    		Inhibitor
    MTHFD2-IN-8 is a selective MTHFD2 inhibitor with an IC50 of 0.066 μM. MTHFD2-IN-8 directly binds to intracellular mitochondrially localized protein MTHFD2 and accumulates selectively in tumor mitochondria. MTHFD2-IN-8 increases intracellular ROS levels, induces mitochondrial membrane potential depolarization, arrests cell cycle at G0/G1 phase, promotes apoptosis in cancer cells. MTHFD2-IN-8 inhibits tumor growth in a mouse colon cancer graft model.
    MTHFD2-IN-8
  • HY-182284
    Anticancer agent 310
    		Inhibitor
    Anticancer agent 310 is an antitumor agent. Anticancer agent 310 releases nitric oxide to induce mitochondrial ROS burst, triggers mitochondrial dysfunction and activates the Bax/Bcl-2-Cyt c-Caspase-9/Caspase-3 apoptotic pathway. Anticancer agent 310 also reduces the levels of SHMT2 and MTHFD2, decreases the ratios of NADPH/NADP+ and GSH/GSSG, thereby disrupting redox homeostasis and exacerbating intracellular ROS accumulation. Anticancer agent 310 can be used in research related to gastric cancer.
    Anticancer agent 310
  • HY-149828
    MTHFD2-IN-4
    		Inhibitor
    MTHFD2-IN-4, tricyclic coumarin derivative, is a potent MTHFD2 inhibitor. MTHFD2-IN-4 can be used in research of cancer.
    MTHFD2-IN-4
  • HY-149825
    MTHFD2-IN-1
    		Inhibitor
    MTHFD2-IN-1 (compound 12) is a potent methylenetetrahydrofolate dehydrogenase (MTHFD2) inhibitor.
    MTHFD2-IN-1
  • HY-149828A
    MTHFD2-IN-4 sodium
    		Inhibitor
    MTHFD2-IN-4 sodium, tricyclic coumarin derivative, is a potent MTHFD2 inhibitor. MTHFD2-IN-4 sodium can be used in research of cancer.
    MTHFD2-IN-4 sodium
  • HY-170361
    MTHFD2-IN-5
    		Inhibitor
    MTHFD2-IN-5 (Compound 16e) is a selective MTHFD2 inhibitor with an IC50 of 66 nM. MTHFD2-IN-5 selectively inhibits MTHFD2. MTHFD2-IN-5 exhibits anticancer activity against acute myeloid leukemia. MTHFD2-IN-5 acts synergistically with Alimta to inhibit the proliferation of acute myeloid leukemia cells.
    MTHFD2-IN-5
  • HY-149826
    MTHFD2-IN-2
    		Inhibitor
    MTHFD2-IN-2 (compound 13) is a potent methylenetetrahydrofolate dehydrogenase (MTHFD2) inhibitor.
    MTHFD2-IN-2
  • HY-172910
    MTHFD2-IN-6
    		Inhibitor
    MTHFD2-IN-6 (compound 41) is a potent and selective MTHFD2 inhibitor. MTHFD2-IN-6 inhibits MTHFD1 and MTHFD2 with IC50s of 19.05 and 1.46 μM, respectively.
    MTHFD2-IN-6
  • HY-149827
    MTHFD2-IN-3
    		Inhibitor
    MTHFD2-IN-3 (compound 10) is a potent methylenetetrahydrofolate dehydrogenase (MTHFD2) inhibitor.
    MTHFD2-IN-3
  • HY-182356
    MTHFD1/2-IN-1
    		Inhibitor
    MTHFD1/2-IN-1 is an orally active dual MTHFD1/MTHFD2 inhibitor, with IC50 values of 0.26 μM and 0.031 μM against human MTHFD1 and MTHFD2, respectively. MTHFD1/2-IN-1 blocks one-carbon metabolism by inhibiting the dehydrogenase activity of MTHFD1 as well as the dehydrogenase and cyclohydrolase activities of MTHFD2, thereby disrupting nucleotide biosynthesis and redox homeostasis in cancer cells. MTHFD1/2-IN-1 exhibits favorable Caco-2 permeability and hepatic microsomal metabolic stability. MTHFD1/2-IN-1 shows significant anti-leukemic activity, which not only reduces the viability of various leukemia cells but also inhibits tumor growth of acute myeloid leukemia (AML) in mouse models.
    MTHFD1/2-IN-1
  • HY-101943R
    LY 345899 (Standard)
    LY 345899 (Standard) is the analytical standard of LY 345899 (HY-101943). This product is intended for research and analytical applications. LY 345899 is a Folate analog and is a methylene tetrahydrofolate dehydrogenase (MTHFD1; DC301) and MTHFD2 inbhibitor with IC50 values of 96 nM and 663 nM, respectively and a Ki of 18 nM for MTHFD1.
    LY 345899 (Standard)
  • HY-148014
    TH7299
    		Inhibitor
    TH7299 is a TbFolD inhibitor with antiparasitic activity. TH7299 binds the tetrahydrofolate-binding pocket of MTHFD2, and inhibits MTHFD2L and the dehydrogenase/cyclohydrolase domain of MTHFD1. TH7299 reduces cancer cells viability, induces apoptosis, DNA damage. TH7299 can be used for the researches of african trypanosomiasis and acute myeloid leukemia.
    TH7299