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
    		99.95%
    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 MTHFD1, MTHFD2 and MTHFD2L, with IC50 values of 0.5 nM, 11 nM and 27 nM, respectively. TH9028 reduces replication fork speed, induces replication stress, triggers S-phase arrest, initiates apoptosis, impairs thymidine production, and causes erroneous uracil incorporation into DNA. TH9028 can be used in research related to acute myeloid leukemia.
    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