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 (52):

Cat. No. Product Name Effect Purity
  • HY-D0186
    2'-Deoxyuridine Inhibitor
    2’-deoxyuridine is a brain-penetrant pyrimidines nucleotide that is associated with nervous system diseases. 2'-Deoxyuridine could increase chromosome breakage and results in a decreased thymidylate synthetase activity. 2'-Deoxyuridine is a precursor in the synthesis of Edoxudine (HY-B1011) and also an analogue of 5-ethynyl-2'-deoxyuridine, EdU (HY-118411). 2’-deoxyuridine reduces microglial activation and improve oxidative stress damage by modulating glycolytic metabolism on the Aβ25-35-induced brain injury, which is promising for research of Alzheimer’s disease (AD)[1][2][3].
  • HY-A0063A
    Tipiracil Inhibitor 99.98%
    Tipiracil is a thymidine phosphorylase (TPase) inhibitor.
  • HY-10821
    Raltitrexed Inhibitor
    Raltitrexed is an antimetabolite agent used in chemotherapy, acting by inhibiting thymidylate synthase.
  • HY-A0061
    Trifluridine Inhibitor
    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[1][2][3][4].
  • HY-16478
    Trifluridine/tipiracil hydrochloride mixture Inhibitor
    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[1][2].
  • HY-172172
    TS-IN-6 Inhibitor
    TS-IN-6 (Compound 10) is a thymidylate synthase (TS) inhibitor with an IC50 value of 0.54  μM, demonstrating significant antiproliferative activity. TS-IN-6 induces G1 phase cell cycle arrest and apoptosis (marked by substantial increases in both early and late apoptotic rates) and shows potential for research on cancers such as colon, breast, and liver cancers[1].
  • HY-N14161
    Diazaquinomycin A Inhibitor
    Diazaquinomycin A (DAQA), a diaza-anthracene antibiotic, is a thymidylate synthase inhibitor. Diazaquinomycin A (DAQA) induces DNA damage, cell cycle arrest, and apoptosis through cleaved-PARP[1].
  • HY-10823
    OSI-7904L Inhibitor
    OSI-7904L (GW1843) is a noncompetitive inhibitor of thymidylate synthase (TS). OSI-7904L is an antifolate compound and a substrate for folylpolyglutamate synthetase. OSI-7904L has cytotoxicity against solid tumor lines, and the toxicity can be selectively blocked by folic acid[1].
  • HY-146699
    MtTMPK-IN-5 Inhibitor
    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[1].
  • HY-149849
    TS-IN-2 Inhibitor
    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[1].
  • HY-170648
    TS-IN-5 Inhibitor
    TS-IN-5 (Compound 15) is a thymidylate synthase (TS) inhibitor. TS-IN-5 induces Apoptosis by modulating Bax, BCL-2, PI3K, and STAT1 proteins. TS-IN-5 shows antitumor effects against liver, breast and colon cancers[1].
  • HY-10822
    Idetrexed Inhibitor
    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[1][2].
  • HY-108474
    Nolatrexed dihydrochloride Inhibitor 98.38%
    Nolatrexed dihydrochloride (AG 337) is an orally active and non-competitive lipophilic inhibitor of thymidylate synthase with a Ki of 11 nM for human thymidylate synthase. Nolatrexed dihydrochloride interacts at the folate cofactor binding site of the enzyme. Nolatrexed dihydrochloride increases sulfotransferases. Nolatrexed dihydrochloride induces cell cycle arrest in S phase of cancer cells. Nolatrexed dihydrochloride exhibits anticancer activity against cervical cancer.
  • HY-120293
    CB30900 Inhibitor
    CB30900 is an inhibitor for thymidylate synthase with an IC50 of 0.2 μM. CB30900 exhibits cytotoxicity in W1L2 with an IC50 of 0.13 μM[1][2].
  • HY-16110
    Tegafur-Uracil Inhibitor 99.77%
    Tegafur-Uracil (UFT; BMS-200604) is an effective oral chemotherapy drug based on fluoropyrimidine. Tegafur-Uracil inhibits thymidylate synthase. Tegafur-Uracil can be used in combination with leucovorin (LV) and polysaccharide K (PSK) for research on solid tumors[1][2].
  • HY-162698
    JMF4073 Inhibitor
    JMF4073 is a thymidylate (TMP) and cytidylate (CMP) kinases inhibitor with IC50s of 0.16 μM and 0.17 μM, respectively. JMF4073 eliminates wild-type (WT)-Bcr-Abl-transformed myeloid cells in vitro and in vivo[1].
  • HY-124093
    8-Deazahomofolic acid Inhibitor
    8-Deazahomofolic acid is an inhibitor of thymidylate synthase (TS) and other folate-related enzymes. 8-Deazahomofolic acid shows inhibitory activity against folate-dependent S. faecium, L. casei, and MTX (HY-14519) resistant strains. 8-Deazahomofolic acid also inhibits the growth of L1210 leukemia cells, with an IC50 value of 87.5 μM. 8-Deazahomofolic acid can be used in research on bacterial infections and tumors[1].
  • HY-123259
    CB3731
    CB3731 is an analogue of N-10-(fluoroethyl)quinazolinylfolate and can be used for fluorine-19 nuclear magnetic resonance studies of binary and ternary complexes of thymidylate synthase[1].
  • HY-A0061S
    Trifluridine-13C,15N2
    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-106168
    Thymectacin 98.21%
    Thymectacin (NB1011) is an agent selectively targeting tumor cells that have a high expression of thymidylate synthase (TS). Thymectacin is an aryloxy phosphoramidate derivative of BVdU (brivudin)[1][2].