1. Signaling Pathways
  2. Apoptosis
  3. Thymidylate Synthase

Thymidylate Synthase

Thymidylate synthase (TSase) is a key enzyme in cell proliferation as it catalyzes a reaction essential for DNA replication, a reductive methylation of 2′-deoxyuridine-5′-monophosphate (dUMP) to form 2′-deoxythymidine-5′-monophosphate (dTMP) using the co-substrate N5,N10-methylene-5,6,7,8-tetrahydrofolate (CH2H4F).

The activity and expression of TSase are tightly controlled throughout the cell cycle, particularly at the translational level. The TSase protein itself binds to the TSase mRNA both at the translational start site (TSS) and in the coding region, inhibiting translational processing of the message. TSase can also bind to the mRNA of at least nine other important gene products, including those of p53 and c-myc. Therefore, manipulating the level of the TSase protein could induce a cascade of consequential effects on cell growth. Because of its importance in DNA precursor synthesis and repair, TSase has proved to be an important target for many chemotherapeutic and antibiotic drugs. Structural analogs of dUMP (e.g., fluoropyrimidines) and CH2H4F (e.g., antifolates) are well-established drugs targeting thymidylate synthase.

Thymidylate Synthase Related Products (26):

Cat. No. Product Name Effect Purity
  • HY-16478
    Trifluridine/tipiracil hydrochloride mixture
    Inhibitor 99.99%
    Trifluridine/tipiracil hydrochloride mixture (TAS-102) is a potent and orally active nucleoside antitumor agent. The composition of Trifluridine/tipiracil hydrochloride mixture (TAS-102) is a 1:0.5 mixture (on a molar basis) of alpha,alpha,alpha-tri-fluorothymidine (FTD) and thymidine phosphorylase inhibitor (TPI). Trifluridine/tipiracil hydrochloride mixture (TAS-102) shows the antitumor activity mainly via the inhibition of thymidylate synthase (TS) and incorporation into DNA.
  • HY-10821
    Inhibitor 99.49%
    Raltitrexed is an antimetabolite agent used in chemotherapy, acting by inhibiting thymidylate synthase.
  • HY-A0061
    Inhibitor 99.98%
    Trifluridine (Trifluorothymidine) is an irreversible and orally active thymidylate synthase inhibitor, and thereby suppressing DNA synthesis. Trifluridine is an antiviral molecule used for research of HSV, rhabdovirus and orthopoxvirus infection. Trifluridine induces cell apoptosis and autophagy. Trifluridine is also an anticancer agent used in studies of metastatic colorectal cancer, gastrointestinal tumors.
  • HY-A0063A
    Tipiracil is a thymidine phosphorylase (TPase) inhibitor.
  • HY-B0021
    Inhibitor 99.91%
    Doxifluridine has anticancer activity. Doxifluidine is a 5-FU prodrug. Doxifluridine is a thymidine synthase inhibitor. Doxifluridine can enhance tumor inhibition by synergizing with a variety of drugs.
  • HY-149849
    TS-IN-2 (compound 17) is a thymidylate synthase (TS) inhibitor with an IC50 of 0.81 μM. TS-IN-2 induces cancer cell apoptosis and cell cycle arrest in S phase, and also inhibit DNA synthesis, resulting in DNA damage.
  • HY-149352
    DG1 (Compound 8Nc) is a Thymidylate Synthase (TS) inhibitor that affects cancer angiogenesis and metabolic reprogramming in NSCLC cells. DG1 can effectively inhibit the expression of CD26, ET-1, FGF-1 and EGF. DG1 also effectively inhibits the proliferation of cancer tissue in the A549 xenograft mouse model.
  • HY-108474
    Nolatrexed dihydrochloride
    Inhibitor 98.54%
    Nolatrexed dihydrochloride (AG 337) is a non-competitive lipophilic inhibitor of thymidylate synthase, interacts at the folate cofactor binding site of the enzyme, with a Ki of 11 nM for human thymidylate synthase. Nolatrexed dihydrochloride (AG 337) induces cell cycle arrest in S phase of cancer cells. Anti-cancer activity.
  • HY-109115
    Fosifloxuridine nafalbenamide
    Fosifloxuridine nafalbenamide (NUC-3373), a pyrimidine nucleotide analogue, is a Thymidylate synthase inhibitor. Fosifloxuridine nafalbenamide has anticancer activity. Fosifloxuridine nafalbenamide has the potential to evoke a host immune response and enhance immunoresearch.
  • HY-143207
    10-Formyl-5,8-dideazafolic acid
    10-Formyl-5,8-dideazafolic acid is a thymidylate synthase inhibitor.
  • HY-13728
    Inhibitor 98.00%
    Plevitrexed (ZD 9331; BGC 9331) is an orally active and potent thymidylate synthase (TS) inhibitor with a Ki of 0.44 nM. Plevitrexed is taken up via the α-folate receptor as well as the reduced folate carrier. Plevitrexed is used for gastric cancer in clinical. Plevitrexed is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
  • HY-10822
    Idetrexed is a thymidylate synthase inhibitor specifically transported into alpha-folate receptor (alpha-FR)-overexpressing tumors. BGC 945 inhibited thymidylate synthase with a Ki of 1.2 nmol/L.
  • HY-146699
    MtTMPK-IN-5 (compound 17) is a potent M. tuberculosis thymidylate kinase (MtbTMPK) inhibitor with an IC50 value of 34 μM. MtTMPK-IN-5 combines favorable enzyme inhibitory activity with significant activity against M. tuberculosis (MIC = 12.5 μM). MtTMPK-IN-5 can be used for researching tuberculosis.
  • HY-A0061S
    Trifluridine-13C,15N2 is the 13C and 15N labeled Trifluridine[1]. Trifluridine (Trifluorothymidine;5-Trifluorothymidine;TFT) is an irreversible thymidylate synthase inhibitor, and thereby suppresses DNA synthesis. Trifluridine is an antiviral agent for herpes simplex virus (HSV) infection. Trifluorothymidine also has anti-orthopoxvirus activity[2].
  • HY-144664
    MtTMPK-IN-2 (compound 15) is a potent Mycobacterium tuberculosis thymidylate kinase (MtTMPK) inhibitor with an IC50 value of 1.1 μM. MtTMPK-IN-2 has inhibitory activity against Mtb H37Rv (MIC = 12.5 μM). MtTMPK-IN-2 exhibits certain cytotoxicity in human fibroblast cells MRC-5 (EC50 = 6.1 μM). MtTMPK-IN-2 can be used for researching tuberculosis.
  • HY-144663
    MtTMPK-IN-1 (compound 3) is a potent Mycobacterium tuberculosis thymidylate kinase (MtTMPK) inhibitor with an IC50 value of 2.5 μM. MtTMPK-IN-1 has moderate to weak activity against Mtb H37Rv and low cytotoxicity in human fibroblast cells MRC-5. MtTMPK-IN-1 can be used for researching tuberculosis.
  • HY-W142014
    N,O-Didansyl-L-tyrosine cyclohexylammonium
    N,O-Didansyl-L-tyrosine cyclohexylammonium is a potent selective thymidylate synthase (TS) inhibitor, acts on TS of Escherichia coli, Lactobacillus casei and human with the IC50 values of 5.0, 3.4 and 119 μM, respectively.
  • HY-146239
    EGFR/HER2/TS-IN-2 (compound 17) is a potent EGFR/HER2 and TS (Thymidylate synthase) inhibitor, with IC50 values of 0.173, 0.125, and 1.12 μM, respectively. EGFR/HER2/TS-IN-2 shows cytotoxic activity against MDA-MB-231 cancer cell lines, with an IC50 of 1.69 µM.
  • HY-10822A
    ONX 0801 trisodium
    ONX 0801 (BGC 945) trisodium is a thymidylate synthase (TS) inhibitor, targeted to α-folate receptor–overexpressing tumors.
  • HY-146702
    MtTMPK-IN-8 (compound 27) is a moderate M. tuberculosis thymidylate kinase (MtbTMPK) inhibitor. MtTMPK-IN-8 has sub-micromolar activity against mycobacteria (MICs = 0.78~9.4 μM) without significant cytotoxicity. MtTMPK-IN-8 can be used for researching tuberculosis.