thymidylate synthase

5-Fluorouracil (5-FU) is a uracil analog, an inhibitor of DNA synthesis. 5-Fluorouracil has antitumor activity and affects pyrimidine synthesis through inhibition of thymidylate synthase. 5-Fluorouracil causes apoptosis and autophagy.

Pemetrexed (LY-231514 Disodium Hydrate), a guanine-derived antineoplastic agent, binds to and inhibits the enzyme thymidylate synthase (TS).

Nolatrexed is a thymidylate synthase inhibitor with potential anticancer activity.

Proguanil hydrochloride (Chloroquanil) is a biguanide compound which metabolizes in the body to form cycloguanil, an anti-malaria agent.Upon hydrolysis, Proguanil hydrochloride is converted to its active cyclic triazine metabolite, cycloguanil, by a cytochrome P450 dependent reaction. Cycloguanil selectively inhibits the bifunctional dihydrofolate reductase-thymidylate synthase of plasmodium parasite, thereby disrupting deoxythymidylate synthesis and ultimately blocking DNA and protein synthesis in the parasite.

Galocitabine (Neofrutulon), a thymidylate synthase inhibitor, is used potentially for the treatment of cancer.

Trifluridine (NSC-75520) is a fluorinated thymidine analog with potential antineoplastic activity. Trifluridine is incorporated into DNA and inhibits thymidylate synthase, resulting in inhibition of DNA synthesis, inhibition of protein synthesis, and apoptosis. This agent also exhibits antiviral activity.

Rac-Belinostat (PX-105684) is a novel hydroxamic acid-type histone deacetylase (HDAC) inhibitor with antineoplastic activity. Belinostat targets HDAC enzymes, thereby inhibiting tumor cell proliferation, inducing apoptosis, promoting cellular differentiation, and inhibiting angiogenesis. This agent may sensitize drug-resistant tumor cells to other antineoplastic agents, possibly through a mechanism involving the down-regulation of thymidylate synthase.

Trifluridine/tipiracil hydrochloride mixture (TAS-102) is a novel oral combination drug containing trifluridine (TFT) and Tipiracil hydrochloride (TTP) in a molar ratio of 2:1.

5-Fluorouracil-13C,15N2 is intended for use as an internal standard for the quantification of 5-flurouracil by GC- or LC-MS. 5-Fluorouracil is a pyrimidine analog that irreversibly inhibits thymidylate synthase, blocking the synthesis of thymidine which is required for DNA synthesis. Intracellular metabolites of 5-fluorouracil exert cytotoxic effects by either inhibiting thymidylate synthetase, or through incorporation into RNA and DNA, ultimately initiating apoptosis.

Thiocoraline is a depsipeptide and DNAbis-intercalator originally isolated fromMicromonosporawith antibacterial and anticancer activities.1,2It is active against the Gram-positive bacteriaS. aureus,B. subtilis, andM. luteus(MICs = 0.05, 0.05, and 0.03 μg/ml, respectively) but not Gram-negativeE. coli,K. pneumoniae, orP. aeruginosa(MICs = >100 μg/ml for all).1Thiocoraline inhibits RNA and DNA polymerase and thymidylate synthase (IC50s = 6, 6, and 15 μg/ml, respectively), as well as RNA and DNA synthesisin vitro(IC50s = 0.008 and 0.4 μg/ml, respectively). It is cytotoxic to P388, A549, HT-29, and MEL-28 cancer cells (IC50s = 0.002, 0.002, 0.01, and 0.002 μg/ml, respectively). 1.Romero, F., Espilego, F., Pérez Baz, J., et al.Thiocoraline, a new depsipeptide with antitumor activity produced by a marine Micromonospora. I. Taxonomy, fermentation, isolation, and biological activitiesJ. Antibiot. (Tokyo)50(9)734-737(1997) 2.Negri, A., Marco, E., García-Hernández, V., et al.Antitumor activity, X-ray crystal structure, and DNA binding properties of thiocoraline A, a natural bisintercalating thiodepsipeptideJ. Med. Chem.50(14)3322-3333(2007)

Amsilarotene (TAC101) inhibits the phosphorylation of retinoblastoma gene product (RB) and increases the presence of 2 cyclin-dependent kinases (CDK) inhibitors resulting in cell cycle arrest. This agent also causes a cytotoxic decline in the thymidylate synthase and cyclin A expression.

ONX 0801 (BGC 945) trisodium is a targeted thymidylate synthase (TS) inhibitor specifically designed to act against tumors overexpressing the α-folate receptor.

CB 3703 is an inhibitor of dihydrofolate reductase and thymidylate synthase.

Fosfluridine tidoxil, a thymidylate synthase inhibitor, is used potentially for the treatment of colorectal cancer, and breast cancer.

Metesind Glucuronate is an antineoplastic. It also is a specific thymidylate synthase inhibitor.

Pemetrexed Diethyl Ester is a protected intermediate in the synthesis of Pemetrexed, a multi-targeted anti-folate that inhibits thymidylate synthase as well as other folate dependent enzymes.

Fosifloxuridine nafalbenamide (NUC 3373), a pyrimidine nucleotide analogue, is a Thymidylate synthase inhibitor. NUC-3373 has anticancer activity. NUC-3373 is a ProTide transformation of 5-FU that generates much higher concentrations of FUDR-MP in patients' cells.

Raltitrexed (D1694)(IC50 of 9 nM), a thymidylate synthase inhibitor, is used for the inhibition of L1210 cell growth.

ANX-510 is a folate-based biomodulator. It stabilizes the covalent binding of the fluorouracil metabolite FdUMP to thymidylate synthase, which results in inhibition of thymidylate synthase, depletion of thymidine triphosphate (TTP), a necessary constituen

5,6,7,8-Tetrahydro-8-deazahomofolic acid is a potential thymidylate synthase (TS) inhibitor and other folate related enzymes inhibitor.

(Rac)-Plevitrexed is a racemate of Plevitrexed. Plevitrexed is an orally active and potent inhibitor of thymidylate synthase (TS).

DG1 (Compound 8Nc), a Thymidylate Synthase (TS) inhibitor, impedes angiogenesis and alters metabolic reprogramming in NSCLC cells, while effectively suppressing the expression of CD26, ET-1, FGF-1, and EGF. Additionally, it notably inhibits cancer tissue proliferation in the A549 xenograft mouse model [1].

BGC-638, an analogue of BGC-945, is a thymidylate synthase inhibitor specifically transported into α-folate receptor (α-FR)–overexpressing tumors.

CB 3731 is used in fluorine-19 nuclear magnetic resonance studies of binary and ternary complexes of thymidylate synthase.

EGFR/HER2/TS-IN-1 are EGFR, HER2 and TS (Thymidylate synthase) inhibitors with IC50 values of 0.203, 0.088 and 0.168 μM, respectively, and have the ability to induce apoptosis (MCF7 cell death).

Tegafur-Uracil is able to be used for anti solid tumors research that is an orally active fluoropyrimidines anticancer agent. Tegafur-Uracil inhibits synthase of thymidylate [1].

8-Deazahomofolic acid is a potential thymidylate synthase (TS) inhibitor and other folate related enzymes inhibitor.

(R)-Plevitrexed is a less active enantiomer of Plevitrexed. Plevitrexed is an orally active and potent inhibitor of thymidylate synthase (TS).

ICI-M247496 is a non-polyglutamated analog of CB3717 and quinazoline-based inhibitor of thymidylate synthase.

Pemetrexed disodium is a guanine-derived antineoplastic agent that functions as a nucleic acid synthesis inhibitor through its binding to, and inhibition of, thymidylate synthase.

Metesind, a thymidylate synthase inhibitor, is used potentially for the treatment of brain cancer and solid tumours.

N,O-Didansyl-L-tyrosine cyclohexylammonium is a potent and selective inhibitor of thymidylate synthase (TS), exhibiting activity against TS from Escherichia coli, Lactobacillus casei, and humans, with IC50 values of 5.0, 3.4, and 119 μM, respectively [1].

5-Fluoroorotic acid is an inhibitor of thymidylate synthase. 5-Fluoroorotic is a selective agent in yeast molecular genetics.5-Fluoroorotic possesses a well-expressed anticandidal effect close to that of 5-fluorocytosine, as well as moderate antidermatophytal effects.

Plevitrexed is taken up via the α-folate receptor as well as the reduced folate carrier. Plevitrexed is an orally active and effective thymidylate synthase (TS) inhibitor (Ki: 0.44 nM). Plevitrexed is used for gastric cancer in clinical.

Proguanil-d6 HCl is a deuterated compound of Proguanil HCl. Proguanil HCl has a CAS number of 637-32-1. Proguanil Hydrochloride is a biguanide compound which metabolizes in the body to form cycloguanil, an anti-malaria agent.Upon hydrolysis, proguanil is converted to its active cyclic triazine metabolite, cycloguanil, by a cytochrome P450 dependent reaction. Cycloguanil selectively inhibits the bifunctional dihydrofolate reductase-thymidylate synthase of plasmodium parasite, thereby disrupting deoxythymidylate synthesis and ultimately blocking DNA and protein synthesis in the parasite.

CB30900 is a novel and effective thymidylate synthase inhibitor.

OSI-7904L is a folate-based thymidylate synthase inhibitor. It also has antimalarial and antitumor properties.

10-Formyl-5,8-dideazafolic acid is a substrate for 10-formyltetrahydrofolate dehydrogenase, an inhibitor of thymidylate synthase.

ICI 198583 is an inhibitor of antifolate thymidylate synthase.

Floxuridine (FUDR) is an antimetabolite, floxuridine inhibits thymidylate synthase, resulting in disruption of DNA synthesis and cytotoxicity.

Nolatrexed dihydrochloride (Thymitaq) is the dihydrochloride salt of nolatrexed, a water-soluble lipophilic quinazoline folate analog with antineoplastic activity. Nolatrexed occupies the folate binding site of thymidylate synthase, resulting in inhibition of thymidylate synthase activity and thymine nucleotide synthesis with subsequent inhibition of DNA replication, DNA damage, S-phase cell cycle arrest, and caspase-dependent apoptosis. This agent also exhibits radiosensitizing activity.