PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 10847455-2 2000 TS has been used as a target for cancer chemotherapy in the development of fluoropyrimidines such as 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine and of novel folate-based TS inhibitors such as ZD1694 (Tomudex, Raltitrexed), ZD9331, LY231514 (ALIMTA, Pemetrexed), AG337 (Thymitaq, Nolatrexed) and AG331. Folic Acid 161-167 thymidylate synthetase Homo sapiens 0-2 10847455-2 2000 TS has been used as a target for cancer chemotherapy in the development of fluoropyrimidines such as 5-fluorouracil (5-FU) and 5-fluorodeoxyuridine and of novel folate-based TS inhibitors such as ZD1694 (Tomudex, Raltitrexed), ZD9331, LY231514 (ALIMTA, Pemetrexed), AG337 (Thymitaq, Nolatrexed) and AG331. Folic Acid 161-167 thymidylate synthetase Homo sapiens 174-176 10573207-2 1999 Raltitrexed (Tomudex), a novel folate-based inhibitor of thymidylate synthase, has demonstrated anti-tumour efficacy comparable with 5-fluorouracil and leucovorin in patients with advanced colorectal cancer (CRC). Folic Acid 31-37 thymidylate synthetase Homo sapiens 57-77 10761765-1 2000 BACKGROUND: Raltitrexed ("Tomudex") is a folate based inhibitor of thymidylate synthase which has been registered in Europe and Australia for the treatment of advanced colorectal cancer. Folic Acid 41-47 thymidylate synthetase Homo sapiens 67-87 10554030-0 1999 Determinants of activity of the antifolate thymidylate synthase inhibitors Tomudex (ZD1694) and GW1843U89 against mono- and multilayered colon cancer cell lines under folate-restricted conditions. Folic Acid 36-42 thymidylate synthetase Homo sapiens 43-63 10554030-6 1999 At nonsaturating substrate concentrations, the catalytic activity of TS was similar in mono- and multilayers grown under high folate conditions but lower in multilayers at saturating concentrations. Folic Acid 126-132 thymidylate synthetase Homo sapiens 69-71 10554030-7 1999 In cells grown under low folate conditions, TS catalytic activity was 3-6-fold lower in multilayers than in monolayers. Folic Acid 25-31 thymidylate synthetase Homo sapiens 44-46 10554030-21 1999 These effects of folate homeostasis may explain some of the variable results seen in treatment of solid tumors with new antifolate TS inhibitors. Folic Acid 17-23 thymidylate synthetase Homo sapiens 131-133 10545786-3 1999 TS has been used as a target for cancer chemotherapy in the development of fluoropyrimidines such as 5-fluorouracil (5FU) and 5-fluorodeoxyuridine and novel folate-based TS inhibitors such as ZD1694 (Tomudex, Raltitrexed), LY231514, AG337 (Thymitaq) and GW1843U89. Folic Acid 157-163 thymidylate synthetase Homo sapiens 0-2 10545786-3 1999 TS has been used as a target for cancer chemotherapy in the development of fluoropyrimidines such as 5-fluorouracil (5FU) and 5-fluorodeoxyuridine and novel folate-based TS inhibitors such as ZD1694 (Tomudex, Raltitrexed), LY231514, AG337 (Thymitaq) and GW1843U89. Folic Acid 157-163 thymidylate synthetase Homo sapiens 170-172 10598551-6 1999 The cytotoxicity of both thymidylate synthase and purine inhibitors requires continued inhibition of target for greater than one generation time, so that the integrative function of FPGS adds considerably to the efficiency of folate antimetabolites. Folic Acid 226-232 thymidylate synthetase Homo sapiens 25-45 10598558-1 1999 Prior studies have indicated that MTA requires intracellular polyglutamation for optimal cytotoxic effect and that these polyglutamates potently inhibit several key enzymes of folate metabolism, including thymidylate synthase (TS), dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase (GARFT). Folic Acid 176-182 thymidylate synthetase Homo sapiens 205-225 9813027-0 1998 Probing the folate-binding site of human thymidylate synthase by site-directed mutagenesis. Folic Acid 12-18 thymidylate synthetase Homo sapiens 41-61 9813027-8 1998 The human TS mutants (I108A and F225W), by virtue of their desirable properties, including good catalytic function and resistance to antifolate TS inhibitors, confirm the importance of amino acid residues Ile-108 and Phe-225 in the binding of folate and its analogues. Folic Acid 137-143 thymidylate synthetase Homo sapiens 10-12 9952321-1 1999 Folic acid (PteGlu)-enhanced intense synergy has been observed between nonpolyglutamylatable dihydrofolate reductase (DHFR) inhibitors and polyglutamylatable inhibitors of other folate-requiring enzymes, such as glycinamide ribonucleotide formyltransferase (GARFT) and thymidylate synthase. Folic Acid 0-10 thymidylate synthetase Homo sapiens 269-289 9952321-1 1999 Folic acid (PteGlu)-enhanced intense synergy has been observed between nonpolyglutamylatable dihydrofolate reductase (DHFR) inhibitors and polyglutamylatable inhibitors of other folate-requiring enzymes, such as glycinamide ribonucleotide formyltransferase (GARFT) and thymidylate synthase. Folic Acid 12-18 thymidylate synthetase Homo sapiens 269-289 9565579-2 1998 Recently, several new and specific thymidylate synthase inhibitors that occupy the folate binding site, including Tomudex(R), BW1843U89, and Thymitaq, have demonstrated therapeutic activity in patients with advanced cancer. Folic Acid 83-89 thymidylate synthetase Homo sapiens 35-55 9479873-8 1997 Selective inhibitors of TS with a folate structure such as raltitrexed could circumvent the resistance by virtue of DHFR overproduction, and this class of compounds which have higher substrate activities for FPGS than MTX may be of value for the treatment of myeloid leukemias in addition to lymphocytic malignancies resistant to conventional chemotherapy. Folic Acid 34-40 thymidylate synthetase Homo sapiens 24-26 9530547-2 1998 Raltitrexed (ZD-1694) is a quinazoline-based folate analogue that exerts its cytotoxic activity by the specific inhibition of thymidylate synthase. Folic Acid 45-51 thymidylate synthetase Homo sapiens 126-146 9762364-1 1998 Chemotherapeutic drugs targeted at folate-dependent reactions have typically been directed at a limited number of target enzymes: dihydrofolate reductase, thymidylate synthase, and GAR and AICAR transformylase. Folic Acid 35-41 thymidylate synthetase Homo sapiens 155-175 9619760-1 1998 PURPOSE: Tomudex is a second-generation folate analogue that when polyglutamated is a potent inhibitor of thymidylate synthase (TS). Folic Acid 40-46 thymidylate synthetase Homo sapiens 106-126 9619760-1 1998 PURPOSE: Tomudex is a second-generation folate analogue that when polyglutamated is a potent inhibitor of thymidylate synthase (TS). Folic Acid 40-46 thymidylate synthetase Homo sapiens 128-130 9436180-5 1998 TS inhibitors nonstructural analog of folate, non-analog antifolate inhibitors (NAAI), are welcome as a new interesting research topic. Folic Acid 38-44 thymidylate synthetase Homo sapiens 0-2 9436180-6 1998 Among the most recent and interesting ones, compounds from Agouron related to the indole structure, are independent on the folate metabolism, highly active and specific for human TS. Folic Acid 123-129 thymidylate synthetase Homo sapiens 179-181 9436180-8 1998 The x-ray crystal structures of some of these inhibitors with TS show that they bind in a different binding site from that of the classical folate TS inhibitors. Folic Acid 140-146 thymidylate synthetase Homo sapiens 62-64 9436180-8 1998 The x-ray crystal structures of some of these inhibitors with TS show that they bind in a different binding site from that of the classical folate TS inhibitors. Folic Acid 140-146 thymidylate synthetase Homo sapiens 147-149 9420019-5 1997 During the past 50 years, many of the enzymes requiring folate as a co-factor (ie, thymidylate synthase), and molecules critical in folate homeostasis (ie, the reduced folate carrier, folylpolyglutamate synthase), have been purified and even crystallized. Folic Acid 56-62 thymidylate synthetase Homo sapiens 83-103 8698629-1 1996 The biological activity and cellular metabolism of ZD1694, a novel folate-based thymidylate synthase (TS) inhibitor, were analyzed in a human leukemia cell line, MOLT-3, and its antifolate-resistant sublines with different mechanisms of resistance to methotrexate (MTX), trimetrexate (TMQ) and N10-propargyl-5,8-dideazafolic acid (CB3717). Folic Acid 67-73 thymidylate synthetase Homo sapiens 80-100 9815766-1 1997 ZD9331 is a drug that was developed from a potent class of water-soluble, C7-methyl-substituted, quinazoline-based inhibitors of thymidylate synthase (TS) that are transported into cells via a saturable, carrier-mediated system (reduced folate carrier, or RFC) but are not substrates for folylpolyglutamate synthetase. Folic Acid 237-243 thymidylate synthetase Homo sapiens 129-149 9147608-0 1997 Folate-based thymidylate synthase inhibitors in cancer chemotherapy. Folic Acid 0-6 thymidylate synthetase Homo sapiens 13-33 9147608-1 1997 Understanding the relationship between chemical structure and biological properties of folate analogs, particularly their interactions with the target enzymes, transport proteins and folate-metabolizing enzyme, folylpolyglutamate synthetase (FPGS), has enabled the rational design and development of the selective thymidylate synthase (TS) inhibitors with folate-based structures for clinical uses. Folic Acid 87-93 thymidylate synthetase Homo sapiens 314-334 8622063-0 1996 Phase I trial of ZD1694, a new folate-based thymidylate synthase inhibitor, in patients with solid tumors. Folic Acid 31-37 thymidylate synthetase Homo sapiens 44-64 9816165-1 1996 Folate analogues that inhibit thymidylate synthase (TS) selectively were developed based on TS and folate molecular structures and properties. Folic Acid 0-6 thymidylate synthetase Homo sapiens 30-50 9816165-1 1996 Folate analogues that inhibit thymidylate synthase (TS) selectively were developed based on TS and folate molecular structures and properties. Folic Acid 99-105 thymidylate synthetase Homo sapiens 30-50 7473577-1 1995 Classical antifolate inhibitors of thymidylate synthase (TS) often require the reduced folate uptake system in order to exert their antitumor effects. Folic Acid 14-20 thymidylate synthetase Homo sapiens 35-55 8958186-1 1996 Folate-based anticancer drugs with specificity for thymidylate synthase (TS) have come of age. Folic Acid 0-6 thymidylate synthetase Homo sapiens 51-71 8567390-1 1995 One of the resistance mechanisms to folate-based thymidylate synthase (TS) inhibitors is the increase in TS activity in tumor cells. Folic Acid 36-42 thymidylate synthetase Homo sapiens 49-69 8567390-1 1995 One of the resistance mechanisms to folate-based thymidylate synthase (TS) inhibitors is the increase in TS activity in tumor cells. Folic Acid 36-42 thymidylate synthetase Homo sapiens 71-73 8567390-1 1995 One of the resistance mechanisms to folate-based thymidylate synthase (TS) inhibitors is the increase in TS activity in tumor cells. Folic Acid 36-42 thymidylate synthetase Homo sapiens 105-107 8898975-0 1996 Amplification of the thymidylate synthase gene in an N10-propargyl-5,8-dideazafolic-acid-resistant human leukemia, MOLT-3 cell line developed in pteroylglutamic acid, but not in leucovorin. Folic Acid 145-165 thymidylate synthetase Homo sapiens 21-41 8898975-2 1996 In this study, effects of reduced and oxidized folates on the development of resistance to a thymidylate synthase (TS) inhibitor, N10-propargyl-5, 8-dideazafolic acid (CB3717), were examined in the human leukemia cell line MOLT-3. Folic Acid 47-54 thymidylate synthetase Homo sapiens 93-113 8898975-8 1996 These results suggest that the types of folates used during the development of CB3717 resistance may play a role in resistance, and that impaired transport of PGA, in CB3717-resistant MOLT-3 cells developed in PGA, might have accelerated amplification of the TS gene. Folic Acid 159-162 thymidylate synthetase Homo sapiens 259-261 8624289-0 1995 Folate-based thymidylate synthase inhibitors as anticancer drugs. Folic Acid 0-6 thymidylate synthetase Homo sapiens 13-33 7495480-1 1995 Quinazoline-based analogues of folic acid are a group of thymidylate synthase (TS) inhibitors that display a wide spectrum of activity for cultured tumour cells, partly due to their differential ability to form polyglutamate metabolites that are (i) more potent TS inhibitors and (ii) not readily effluxed from cells. Folic Acid 31-41 thymidylate synthetase Homo sapiens 57-77 7473577-1 1995 Classical antifolate inhibitors of thymidylate synthase (TS) often require the reduced folate uptake system in order to exert their antitumor effects. Folic Acid 14-20 thymidylate synthetase Homo sapiens 57-59 7796401-4 1995 Systematic structure-activity investigations have led to the discovery and development of ZD1694 (Tomudex), an inhibitor of thymidylate synthase that exploits both the reduced folate carrier and folylpolyglutamate synthetase as major determinants of its growth-inhibitory activity. Folic Acid 176-182 thymidylate synthetase Homo sapiens 124-144 7577040-1 1995 Thymidylate synthase is an important target for both fluorinated pyrimidines and for new folate analogues. Folic Acid 89-95 thymidylate synthetase Homo sapiens 0-20 7577040-3 1995 The 5FU-nucleotide FdUMP induces inhibition of thymidylate synthase which is enhanced and retained for longer in the presence of increased folate pools, for which leucovorin is a precursor. Folic Acid 139-145 thymidylate synthetase Homo sapiens 47-67 7796401-6 1995 An associated structure-activity investigation has led to the development of ZD9331, a potent thymidylate synthase inhibitor which exploits the reduced folate carrier for cell entry, but which is independent of polyglutamation for its thymidylate synthase-inhibitory activity. Folic Acid 152-158 thymidylate synthetase Homo sapiens 94-114 7987985-0 1994 Biochemical effects of folate-based inhibitors of thymidylate synthase in MGH-U1 cells. Folic Acid 23-29 thymidylate synthetase Homo sapiens 50-70 7537518-2 1995 A 500-fold increase in thymidylate synthase (TS) activity is the primary mechanism of resistance to ZD1694 in the W1L2:RD1694 cell line, which is consequently highly cross-resistant to other folate-based TS inhibitors, including BW1843U89, LY231514 and AG337, but sensitive to antifolates with other enzyme targets. Folic Acid 191-197 thymidylate synthetase Homo sapiens 23-43 7537519-0 1995 Molecular characterisation of two cell lines selected for resistance to the folate-based thymidylate synthase inhibitor, ZD1694. Folic Acid 76-82 thymidylate synthetase Homo sapiens 89-109 7537519-2 1995 We have investigated the mechanistic basis for resistance to folate-based thymidylate synthase (TS) inhibitors using two cell lines selected for resistance to ZD1694 (N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N -methylamino]-2 - thenoyl)-L-glutamic acid), a drug currently in phase III clinical trial. Folic Acid 61-67 thymidylate synthetase Homo sapiens 74-94 7537519-2 1995 We have investigated the mechanistic basis for resistance to folate-based thymidylate synthase (TS) inhibitors using two cell lines selected for resistance to ZD1694 (N-(5-[N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N -methylamino]-2 - thenoyl)-L-glutamic acid), a drug currently in phase III clinical trial. Folic Acid 61-67 thymidylate synthetase Homo sapiens 96-98 8053928-5 1994 Addition of the reduced folate leucovorin potentiated the effects induced by FdUrd, indicating that thymidylate synthase inhibition is an important initial step in drug effect followed by DNA fragmentation and suppression of c-myc expression. Folic Acid 24-30 thymidylate synthetase Homo sapiens 100-120 8145235-1 1994 Syntheses of several new inhibitors of thymidylate synthase (TS) structurally related to folic acid are described in which the pterin portion of the folate molecule is replaced by a benzo[f]quinazoline moiety, but which retain the natural methyleneamino link to the benzoylglutamate side chain. Folic Acid 89-99 thymidylate synthetase Homo sapiens 39-59 8145235-1 1994 Syntheses of several new inhibitors of thymidylate synthase (TS) structurally related to folic acid are described in which the pterin portion of the folate molecule is replaced by a benzo[f]quinazoline moiety, but which retain the natural methyleneamino link to the benzoylglutamate side chain. Folic Acid 89-99 thymidylate synthetase Homo sapiens 61-63 8145235-1 1994 Syntheses of several new inhibitors of thymidylate synthase (TS) structurally related to folic acid are described in which the pterin portion of the folate molecule is replaced by a benzo[f]quinazoline moiety, but which retain the natural methyleneamino link to the benzoylglutamate side chain. Folic Acid 149-155 thymidylate synthetase Homo sapiens 39-59 8145235-1 1994 Syntheses of several new inhibitors of thymidylate synthase (TS) structurally related to folic acid are described in which the pterin portion of the folate molecule is replaced by a benzo[f]quinazoline moiety, but which retain the natural methyleneamino link to the benzoylglutamate side chain. Folic Acid 149-155 thymidylate synthetase Homo sapiens 61-63 8145235-6 1994 The excellent combination of TS inhibitory activity, FPGS substrate activity, and affinity for the reduced folate transport system in the most potent of these derivatives, 3e, resulted in IC50 values of 0.2-0.8 nM against these tumor lines. Folic Acid 107-113 thymidylate synthetase Homo sapiens 29-31 8294436-0 1994 Mode of binding of folate analogs to thymidylate synthase. Folic Acid 19-25 thymidylate synthetase Homo sapiens 37-57 8294436-4 1994 Thymidylate synthase bound both mono and polyglutamylated folate substrates and analogs more tightly in the presence of deoxyuridylate. Folic Acid 58-64 thymidylate synthetase Homo sapiens 0-20 8174202-0 1994 Comparative cytotoxicity of folate-based inhibitors of thymidylate synthase and 5-fluorouracil +/- leucovorin in MGH-U1 cells. Folic Acid 28-34 thymidylate synthetase Homo sapiens 55-75 8422641-6 1993 Moreover, these results show that the ratio of 5,10-methylenetetrahydrofolate concentration to thymidylate synthase concentration influences the thymidylate synthase inhibition rate in tumor, and that the new synthesis of 5,10-methylenetetrahydrofolate and tetrahydrofolate from other endogenous reduced folates is also important in tumors with high thymidylate synthase concentrations. Folic Acid 304-311 thymidylate synthetase Homo sapiens 95-115 8399157-0 1993 Fluorine-19 nuclear magnetic resonance studies of binary and ternary complexes of thymidylate synthase utilizing a fluorine-labeled folate analogue. Folic Acid 132-138 thymidylate synthetase Homo sapiens 82-102 8399157-1 1993 Traditional fluorine-19 nuclear magnetic resonance (19F NMR) studies of thymidylate synthase (TS) have utilized the fluorine substituent of 5-fluorodeoxyuridine 5"-monophosphate (FdUMP), a mechanism-based inhibitor of the enzyme, in complexes with various folate and folate analogues in order to establish a paradigm for the formation of binary and ternary complexes. Folic Acid 256-262 thymidylate synthetase Homo sapiens 72-92 8399157-1 1993 Traditional fluorine-19 nuclear magnetic resonance (19F NMR) studies of thymidylate synthase (TS) have utilized the fluorine substituent of 5-fluorodeoxyuridine 5"-monophosphate (FdUMP), a mechanism-based inhibitor of the enzyme, in complexes with various folate and folate analogues in order to establish a paradigm for the formation of binary and ternary complexes. Folic Acid 267-273 thymidylate synthetase Homo sapiens 72-92 8398636-7 1993 These schedules appear to be the most effective in the generation of the higher polyglutamates of 5,10-methylenetetrahydrofolate, the most efficient intracellular folate metabolite for ternary complex formation and TS inhibition. Folic Acid 122-128 thymidylate synthetase Homo sapiens 215-217 8325888-1 1993 We have investigated the mechanism of inactivation of thymidylate synthase (TS) by ICI D1694 (a folate-based quinazoline) in normal versus tumor-derived human mammary epithelial cells. Folic Acid 96-102 thymidylate synthetase Homo sapiens 54-74 8325888-1 1993 We have investigated the mechanism of inactivation of thymidylate synthase (TS) by ICI D1694 (a folate-based quinazoline) in normal versus tumor-derived human mammary epithelial cells. Folic Acid 96-102 thymidylate synthetase Homo sapiens 76-78 8325888-7 1993 5,10-Methylenetetrahydrofolate (via folinic acid), however, did block the effects of ICI D1694, showing that the drug has its effect upon both detainment and enzyme inhibition by binding to the folate substrate site of TS. Folic Acid 24-30 thymidylate synthetase Homo sapiens 219-221 8461049-0 1993 Effect of folate diastereoisomers on the binding of 5-fluoro-2"-deoxyuridine-5"-monophosphate to thymidylate synthase. Folic Acid 10-16 thymidylate synthetase Homo sapiens 97-117 8461049-1 1993 A series of natural and unnatural stereoisomers of reduced folate coenzymes have been studied for their capacity to facilitate binding of 5-fluoro-2"-dUMP (FdUMP) to bacterial thymidylate synthase (TS). Folic Acid 59-65 thymidylate synthetase Homo sapiens 176-196 8461049-1 1993 A series of natural and unnatural stereoisomers of reduced folate coenzymes have been studied for their capacity to facilitate binding of 5-fluoro-2"-dUMP (FdUMP) to bacterial thymidylate synthase (TS). Folic Acid 59-65 thymidylate synthetase Homo sapiens 198-200 8461049-4 1993 These results suggest that folates, which are not a natural cosubstrate for TS, have an additional role in facilitating FdUMP binding to TS. Folic Acid 27-34 thymidylate synthetase Homo sapiens 137-139 8422641-6 1993 Moreover, these results show that the ratio of 5,10-methylenetetrahydrofolate concentration to thymidylate synthase concentration influences the thymidylate synthase inhibition rate in tumor, and that the new synthesis of 5,10-methylenetetrahydrofolate and tetrahydrofolate from other endogenous reduced folates is also important in tumors with high thymidylate synthase concentrations. Folic Acid 304-311 thymidylate synthetase Homo sapiens 145-165 8422641-6 1993 Moreover, these results show that the ratio of 5,10-methylenetetrahydrofolate concentration to thymidylate synthase concentration influences the thymidylate synthase inhibition rate in tumor, and that the new synthesis of 5,10-methylenetetrahydrofolate and tetrahydrofolate from other endogenous reduced folates is also important in tumors with high thymidylate synthase concentrations. Folic Acid 304-311 thymidylate synthetase Homo sapiens 145-165 1548676-1 1992 Antifolate inhibitors of thymidylate synthase (TS) have primarily been based on the structure of folic acid. Folic Acid 97-107 thymidylate synthetase Homo sapiens 25-45 1548676-1 1992 Antifolate inhibitors of thymidylate synthase (TS) have primarily been based on the structure of folic acid. Folic Acid 97-107 thymidylate synthetase Homo sapiens 47-49 2195551-3 1990 Reduced folates (LV and 5-methyltetrahydrofolate) at concentrations greater than or equal to 1 microM can, by raising the intracellular levels of 5,10-methylenetetrahydrofolate, increase and prolong the inhibition of the target enzyme, thymidylate synthase, with formation of a stable ternary complex formed by the enzyme, the folate coenzyme and the fluoropyrimidine inhibitor (5-fluorodeoxyuridylate). Folic Acid 8-14 thymidylate synthetase Homo sapiens 236-256 2195551-3 1990 Reduced folates (LV and 5-methyltetrahydrofolate) at concentrations greater than or equal to 1 microM can, by raising the intracellular levels of 5,10-methylenetetrahydrofolate, increase and prolong the inhibition of the target enzyme, thymidylate synthase, with formation of a stable ternary complex formed by the enzyme, the folate coenzyme and the fluoropyrimidine inhibitor (5-fluorodeoxyuridylate). Folic Acid 8-15 thymidylate synthetase Homo sapiens 236-256 1737372-0 1992 Human lymphoblastoid cells with acquired resistance to C2-desamino-C2-methyl-N10-propargyl-5,8-dideazafolic acid: a novel folate-based thymidylate synthase inhibitor. Folic Acid 122-128 thymidylate synthetase Homo sapiens 135-155 1737372-6 1992 The resistant cell line, W1-L2:C1, was cross-resistant to other folate-based TS inhibitors but was as sensitive as the parent cell line, W1-L2, to 5-fluorodeoxyuridine. Folic Acid 64-70 thymidylate synthetase Homo sapiens 77-79 1889478-3 1991 Folate-deficient cells exhibit a two-fold increase in thymidine kinase and thymidylate synthase activities. Folic Acid 0-6 thymidylate synthetase Homo sapiens 75-95 1897982-2 1991 A radioenzymatic assay based upon entrapment of 5,10-methylenetetrahydrofolate, and other reduced folates after cycling to this form, into a stable ternary complex with thymidylate synthase and tritiated 5-fluoro-2"-deoxyuridine-5"-monophosphate was used to estimate reduced folate metabolites. Folic Acid 98-105 thymidylate synthetase Homo sapiens 169-189 1897982-2 1991 A radioenzymatic assay based upon entrapment of 5,10-methylenetetrahydrofolate, and other reduced folates after cycling to this form, into a stable ternary complex with thymidylate synthase and tritiated 5-fluoro-2"-deoxyuridine-5"-monophosphate was used to estimate reduced folate metabolites. Folic Acid 72-78 thymidylate synthetase Homo sapiens 169-189 2253202-0 1990 Multiple membrane transport systems for the uptake of folate-based thymidylate synthase inhibitors. Folic Acid 54-60 thymidylate synthetase Homo sapiens 67-87 2253202-8 1990 These results indicate that multiple folate transport systems may be involved in the uptake of folate-based thymidylate synthase inhibitors. Folic Acid 37-43 thymidylate synthetase Homo sapiens 108-128 2253202-8 1990 These results indicate that multiple folate transport systems may be involved in the uptake of folate-based thymidylate synthase inhibitors. Folic Acid 95-101 thymidylate synthetase Homo sapiens 108-128 35253073-3 2022 The enzymes Dihydrofolate reductase, thymidylate synthase, and Serine hydroxy methyltransferase play an essential role in the folate pathway. Folic Acid 126-132 thymidylate synthetase Homo sapiens 37-57 33809325-10 2021 Furthermore, we confirmed that the TS 1100T>C polymorphism was synergistic with low folic acid levels (AOR = 6.749, P < 0.0001). Folic Acid 84-94 thymidylate synthetase Homo sapiens 35-37 2523018-2 1989 It has been suggested that CF provides a source of intracellular reduced folates which, in turn, enhances the inhibition of the cellular target thymidylate synthase (TS) by the FP metabolite 5-fluoro-2"-deoxyuridylate (FdUMP). Folic Acid 73-80 thymidylate synthetase Homo sapiens 144-164 3470522-0 1987 Folate analogues as inhibitors of thymidylate synthase. Folic Acid 0-6 thymidylate synthetase Homo sapiens 34-54 3366769-9 1988 The MTX-induced intracellular accumulation of 10-formyl-H2folate and H2folate may play a role in the drug-related cytotoxicity through the contribution of these folates to the inhibition of thymidylate synthase and de novo purine synthesis. Folic Acid 161-168 thymidylate synthetase Homo sapiens 190-210 3247881-2 1988 An increase in the availability of reduced folates necessary for tight binding of FdUMP to thymidylate synthase (TS) contributes to the enhanced cytotoxicity of this drug combination. Folic Acid 43-50 thymidylate synthetase Homo sapiens 91-111 2977717-8 1988 This analysis also suggests that folate analogs inhibitory to thymidylate synthase are more compatible than pyrimidine analogs with inhibition of thymidylate synthase as an approach to cancer chemotherapy. Folic Acid 33-39 thymidylate synthetase Homo sapiens 62-82 2977717-8 1988 This analysis also suggests that folate analogs inhibitory to thymidylate synthase are more compatible than pyrimidine analogs with inhibition of thymidylate synthase as an approach to cancer chemotherapy. Folic Acid 33-39 thymidylate synthetase Homo sapiens 146-166 3470522-5 1987 Comparison of the data for various folate analogues reveals a striking dependence of TS inhibitory potency upon the number of nitrogens in the folate pyrazine ring. Folic Acid 35-41 thymidylate synthetase Homo sapiens 85-87 3517565-0 1986 Tissue folate polyglutamate chain length determination by electrophoresis as thymidylate synthase-fluorodeoxyuridylate ternary complexes. Folic Acid 7-13 thymidylate synthetase Homo sapiens 77-97 2963229-4 1987 The most probable mechanism of the interaction between folinic acid and the fluoropyrimidines is stabilization of thymidylate synthase (TS) in inactive complexes with 5-fluoro-2"-deoxyuridine-5"-monophosphate (FdUMP) and folate cofactor. Folic Acid 221-227 thymidylate synthetase Homo sapiens 114-134 3501543-1 1987 The active metabolite of FUra, 5-fluorodeoxyuridine monophosphate (5-FdUMP), requires the presence of reduced folates to form a covalent ternary complex with the target enzyme thymidylate synthase (TS). Folic Acid 110-117 thymidylate synthetase Homo sapiens 176-196 3501543-1 1987 The active metabolite of FUra, 5-fluorodeoxyuridine monophosphate (5-FdUMP), requires the presence of reduced folates to form a covalent ternary complex with the target enzyme thymidylate synthase (TS). Folic Acid 110-117 thymidylate synthetase Homo sapiens 198-200 7078549-5 1982 In this review, we examine the properties of TSase-dUMP complexes in order to determine if there is an experimental basis for drawing a close analogy between dUMP and FdUMP in their interaction with TSase, and also to evaluate data indicating a potential chemotherapeutic value for TSase-dUMP complexes formed in the presence of folate analogs. Folic Acid 329-335 thymidylate synthetase Homo sapiens 45-50 6351556-4 1983 Analog studies with thymidylate synthase suggest that there are two types of folate binding sites and this led us to propose a model for the subunit association. Folic Acid 77-83 thymidylate synthetase Homo sapiens 20-40 6889511-0 1982 The effect of derivatives of folic acid on the fluorodeoxyuridylate-thymidylate synthetase covalent complex in human colon xenografts. Folic Acid 29-39 thymidylate synthetase Homo sapiens 68-90 4212249-0 1974 Polyglutamyl derivatives of folate as substrates and inhibitors of thymidylate synthetase. Folic Acid 28-34 thymidylate synthetase Homo sapiens 67-89 30572970-2 2019 Genetic disturbances in folate metabolism such as Thymidylate synthase may increase risk for conotruncal heart defects. Folic Acid 24-30 thymidylate synthetase Homo sapiens 50-70 33710891-0 2021 Folic Acid-Peptide Conjugates Combine Selective Cancer Cell Internalization with Thymidylate Synthase Dimer Interface Targeting. Folic Acid 0-10 thymidylate synthetase Homo sapiens 81-101 33710891-2 2021 Accordingly, we have designed conjugates of folic acid with anticancer peptides able to bind human thymidylate synthase (hTS) and enter cancer cells through folate receptor alpha (FRalpha) highly expressed by several cancer cells. Folic Acid 44-54 thymidylate synthetase Homo sapiens 99-119 33391382-0 2021 Variants of Genes Involved in Metabolism of Folate Among Patients with Breast Cancer: Association of TYMS 3R Allele with Susceptibility to Breast Cancer and Metastasis. Folic Acid 44-50 thymidylate synthetase Homo sapiens 101-105 31739736-1 2020 INTRODUCTION: Raltitrexed is a folate analogue, which selectively inhibits thymidylate synthase, used in the treatment of colorectal carcinoma. Folic Acid 31-37 thymidylate synthetase Homo sapiens 75-95 31873125-4 2019 Methotrexate (MTX) and pemetrexed (PTX) are two examples of antifolates that have cured many patients over the years but target different enzymes from the folate cycle (mainly dihydrofolate reductase and thymidylate synthase, respectively). Folic Acid 64-70 thymidylate synthetase Homo sapiens 204-224 31542479-4 2019 Here we found that the expression of dihydrofolate reductase (DHFR) and thymidylate synthetase (TYMS), which played an essential role in folate metabolism and several types of tumors, were up-regulated in both human glioma tissues and cell lines, and overexpression of DHFR/TYMS promoted the proliferation of glioma cells. Folic Acid 44-50 thymidylate synthetase Homo sapiens 72-94 31542479-4 2019 Here we found that the expression of dihydrofolate reductase (DHFR) and thymidylate synthetase (TYMS), which played an essential role in folate metabolism and several types of tumors, were up-regulated in both human glioma tissues and cell lines, and overexpression of DHFR/TYMS promoted the proliferation of glioma cells. Folic Acid 44-50 thymidylate synthetase Homo sapiens 96-100 31542479-4 2019 Here we found that the expression of dihydrofolate reductase (DHFR) and thymidylate synthetase (TYMS), which played an essential role in folate metabolism and several types of tumors, were up-regulated in both human glioma tissues and cell lines, and overexpression of DHFR/TYMS promoted the proliferation of glioma cells. Folic Acid 44-50 thymidylate synthetase Homo sapiens 274-278 29922516-0 2018 A novel thymidylate synthase from the Vibrionales, Alteromonadales, Aeromonadales, and Pasteurellales (VAAP) clade with altered nucleotide and folate binding sites. Folic Acid 143-149 thymidylate synthetase Homo sapiens 8-28 29162511-4 2018 METHODS: We investigated if major polymorphisms of folate-related genes, namely MTHFR c.677C>T, MTR c.2756A>G, MTRR c.66A>G and TYMS TSER (a 28-bp tandem repeat in the 5" promoter enhancer region of TYMS) increase the risk of pathological changes of the thymus in AChR+ MG patients. Folic Acid 51-57 thymidylate synthetase Homo sapiens 128-132 29162511-4 2018 METHODS: We investigated if major polymorphisms of folate-related genes, namely MTHFR c.677C>T, MTR c.2756A>G, MTRR c.66A>G and TYMS TSER (a 28-bp tandem repeat in the 5" promoter enhancer region of TYMS) increase the risk of pathological changes of the thymus in AChR+ MG patients. Folic Acid 51-57 thymidylate synthetase Homo sapiens 199-203 28939595-0 2017 Dihydrofolate Reductase/Thymidylate Synthase Fine-Tunes the Folate Status and Controls Redox Homeostasis in Plants. Folic Acid 60-66 thymidylate synthetase Homo sapiens 24-44 29360079-1 2018 Methotrexate is an antimetabolite analog to folic acid that competitively inhibits the enzyme dihydrofolate reductase and thymidylate synthetase, essential for the synthesis of DNA and RNA. Folic Acid 44-54 thymidylate synthetase Homo sapiens 122-144 29321350-8 2017 The restoration of one-carbon homeostasis by SHMT1 C1420T or increased flux of folate towards remethylation due to TYMS 5"-UTR 28 bp tandem repeat or nonvegetarian diet can lower homocysteine levels. Folic Acid 79-85 thymidylate synthetase Homo sapiens 115-119 28939595-3 2017 This work presents a complete study of a plant DHFR-TS (dihydrofolate reductase-thymidylate synthase) gene family that implements the penultimate step in folate biosynthesis. Folic Acid 63-69 thymidylate synthetase Homo sapiens 80-100 28338744-1 2017 Most species, such as humans, have monofunctional forms of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) that are key folate metabolism enzymes making critical folate components required for DNA synthesis. Folic Acid 96-102 thymidylate synthetase Homo sapiens 59-79 28043790-1 2017 BACKGROUND: Thymidylate synthase (TYMS), a key rate-limiting enzyme in the folate metabolism, plays essential roles in the development of several malignancies including hepatocellular carcinoma (HCC). Folic Acid 75-81 thymidylate synthetase Homo sapiens 12-32 28043790-1 2017 BACKGROUND: Thymidylate synthase (TYMS), a key rate-limiting enzyme in the folate metabolism, plays essential roles in the development of several malignancies including hepatocellular carcinoma (HCC). Folic Acid 75-81 thymidylate synthetase Homo sapiens 34-38 28685068-0 2017 Protein and mRNA expression of folic acid-associated enzymes as biomarkers for the cytotoxicity of the thymidylate synthase-targeted drugs, pemetrexed and S-1, in non-small cell lung cancer. Folic Acid 31-41 thymidylate synthetase Homo sapiens 103-123 28685068-1 2017 The thymidylate synthase (TS)-targeted drugs, pemetrexed and S-1, exert an important role in advanced non-small cell lung cancer (NSCLC) treatment; folic acid-associated enzymes are expected to behave as biomarkers, although their role has yet to be fully elucidated. Folic Acid 148-158 thymidylate synthetase Homo sapiens 4-24 28685068-1 2017 The thymidylate synthase (TS)-targeted drugs, pemetrexed and S-1, exert an important role in advanced non-small cell lung cancer (NSCLC) treatment; folic acid-associated enzymes are expected to behave as biomarkers, although their role has yet to be fully elucidated. Folic Acid 148-158 thymidylate synthetase Homo sapiens 26-28 28338744-1 2017 Most species, such as humans, have monofunctional forms of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) that are key folate metabolism enzymes making critical folate components required for DNA synthesis. Folic Acid 133-139 thymidylate synthetase Homo sapiens 59-79 25668494-7 2015 The results of the docking studies show that 2 could bind and inhibit both thymidylate synthase (TS) and the two folate-dependent purine biosynthetic enzymes (GARFTase and AICARFTase), which is consistent with the results of in vitro metabolic assays. Folic Acid 113-119 thymidylate synthetase Homo sapiens 75-95 27637357-3 2016 In the treatment of cancer with 5-fluorouracil, the administration of folates mechanistically leads to the formation of [6R]-5,10-methylene-tetrahydrofolate, and the increased concentration of this molecule leads to stabilization of the ternary complex comprising thymidylate synthase, 2"-deoxy-uridine-5"-monophosphate, and [6R]-5,10-methylene-tetrahydrofolate. Folic Acid 70-77 thymidylate synthetase Homo sapiens 264-284 27637357-5 2016 Modulation of thymidylate synthase activity became central in the study of folate/cytotoxic combinations and, despite wide use, research into the folate component was neglected, leaving important questions unanswered. Folic Acid 75-81 thymidylate synthetase Homo sapiens 14-34 26438060-1 2016 The 5,10-methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) are critical enzymes in folate metabolism. Folic Acid 28-34 thymidylate synthetase Homo sapiens 79-81 26438060-3 2016 We investigated the risks of adult leukemia with genetic polymorphisms of folate metabolic enzymes (MTHFR C677T, A1298C, and TS) and evaluated if the associations varied by dietary folate intake from a multicenter case-control study conducted in Chinese. Folic Acid 74-80 thymidylate synthetase Homo sapiens 125-127 26438060-9 2016 Stratified analysis by dietary folate intake showed the increased risks of leukemia with the MTHFR 677TT and TS 2R3R/2R2R genotypes were only significant in individuals with low folate intake. Folic Acid 31-37 thymidylate synthetase Homo sapiens 109-111 26438060-9 2016 Stratified analysis by dietary folate intake showed the increased risks of leukemia with the MTHFR 677TT and TS 2R3R/2R2R genotypes were only significant in individuals with low folate intake. Folic Acid 178-184 thymidylate synthetase Homo sapiens 109-111 26438060-10 2016 A significant interaction between TS polymorphism and dietary folate intake was observed (P = 0.03). Folic Acid 62-68 thymidylate synthetase Homo sapiens 34-36 26438060-11 2016 This study suggests that dietary folate intake and gender may modify the associations between MTHFR/TS polymorphisms and adult leukemia risk. Folic Acid 33-39 thymidylate synthetase Homo sapiens 100-102 24756984-1 2015 Thymidylate synthase (TYMS) plays a crucial role in folate metabolism as well as DNA synthesis and repair. Folic Acid 52-58 thymidylate synthetase Homo sapiens 0-20 24756984-1 2015 Thymidylate synthase (TYMS) plays a crucial role in folate metabolism as well as DNA synthesis and repair. Folic Acid 52-58 thymidylate synthetase Homo sapiens 22-26 24166930-1 2015 Thymidylate synthase (TYMS) is involved in the folate metabolism and provision of nucleotides needed for DNA synthesis and repair. Folic Acid 47-53 thymidylate synthetase Homo sapiens 0-20 24166930-1 2015 Thymidylate synthase (TYMS) is involved in the folate metabolism and provision of nucleotides needed for DNA synthesis and repair. Folic Acid 47-53 thymidylate synthetase Homo sapiens 22-26 26096018-2 2016 The human thymidylate synthase and dihydrofolate reductase catalyze two consecutive reactions in the folate metabolism pathway, and experiments have shown that they are very likely to bind in the same multi-enzyme complex in vivo. Folic Acid 42-48 thymidylate synthetase Homo sapiens 10-30 25066213-4 2014 Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT, and TYMS, also interacted significantly with folate in a multivariant analysis (corrected p = 9.9 x 10-6) but collectively explained only 0.2% of OC risk. Folic Acid 117-123 thymidylate synthetase Homo sapiens 76-80 25245820-2 2015 Thymidylate (dTMP) is catalyzed by thymidylate synthase (TS) using the folate-derived one-carbon unit as the sole methyl donor. Folic Acid 71-77 thymidylate synthetase Homo sapiens 35-55 25341694-4 2014 The role of folic acid in carcinogenesis may be modulated by polymorphism C677T in MTHFR and tandem repeats 2R/3R in the promoter site of TYMS gene that are related to decreased enzymatic activity and quantity and availability of the enzyme, respectively. Folic Acid 12-22 thymidylate synthetase Homo sapiens 138-142 22147344-8 2013 SHMT and TYMS variants were found to decrease oxidative stress by increasing the folate pool (r = 0.38, P = 0.003) and also by increasing the antioxidant status (r = 0.28, P = 0.03). Folic Acid 81-87 thymidylate synthetase Homo sapiens 9-13 24771227-3 2014 The aim of this study was to investigate whether the genetic polymorphisms MTHFR C677T and A1298C, MTR A2756G, TYMS 2R/3R and SLC19A1 G80A, involved in folate metabolism, increase the risk of neuroblastoma in Brazilian children. Folic Acid 152-158 thymidylate synthetase Homo sapiens 111-115 24053355-1 2013 Most species, such as humans, have monofunctional forms of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) that are key folate metabolism enzymes making critical folate components required for DNA synthesis. Folic Acid 96-102 thymidylate synthetase Homo sapiens 59-79 24053355-1 2013 Most species, such as humans, have monofunctional forms of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) that are key folate metabolism enzymes making critical folate components required for DNA synthesis. Folic Acid 133-139 thymidylate synthetase Homo sapiens 59-79 23726796-2 2013 In the folate pathway, TYMS catalyzes the methylation of deoxyuridylate to deoxythymidylate using 5,10-methylenetetrahydrofolate [5,10-CH2=THF, derived from tetrahydrofolate (THF)], as a cofactor. Folic Acid 7-13 thymidylate synthetase Homo sapiens 23-27 23893618-7 2013 Two TYMS SNPs (rs16948305 and rs495139) exhibited significant (P = 0.024 and P = 0.040, respectively) gene-diet interactions with folate intake. Folic Acid 130-136 thymidylate synthetase Homo sapiens 4-8 23611499-4 2013 Examination of the crystal structures identifies a Mg(2+) near the glutamyl moiety of the folate cofactor, providing the first structural evidence for Mg(2+) binding to TSase. Folic Acid 90-96 thymidylate synthetase Homo sapiens 169-174 22576918-1 2012 Thymidylate synthase (TS) is a crucial enzyme in folate metabolism and plays a vital role in DNA synthesis and repair. Folic Acid 50-56 thymidylate synthetase Homo sapiens 0-20 23449276-3 2013 Pemetrexed is an antifolate inhibiting different folate pathway genes (thymidylate synthase [TS], dihydrofolate reductase, glycinamide ribonucleotide formyltransferase [GARFT], and aminoimidazole carboxamide ribonucleotide formyltransferase, [AICARFT]). Folic Acid 21-27 thymidylate synthetase Homo sapiens 71-91 23019356-0 2012 Folate binding site of flavin-dependent thymidylate synthase. Folic Acid 0-6 thymidylate synthetase Homo sapiens 40-60 22484375-6 2012 The elevate expression of dihydrofolate reductase and thymidylate synthase, two E2F1-target genes involved in folate metabolism and required for G(1) progression, favored dTTP accumulation, which promoted DNA single strand breaks and the subsequent activation of Chk1. Folic Acid 33-39 thymidylate synthetase Homo sapiens 54-74 23336575-1 2013 OBJECTIVE: Polymorphisms that reduce the activity of reduced folate carrier (RFC) and methylenetetrahydrofolate reductase (MTHFR) and double (2R2R) or triple (3R3R) 28-bp tandem repeats in the promoter region of thymidylate synthase (TS) have been associated with the risk of childhood acute leukemia (AL). Folic Acid 61-67 thymidylate synthetase Homo sapiens 212-232 23336575-1 2013 OBJECTIVE: Polymorphisms that reduce the activity of reduced folate carrier (RFC) and methylenetetrahydrofolate reductase (MTHFR) and double (2R2R) or triple (3R3R) 28-bp tandem repeats in the promoter region of thymidylate synthase (TS) have been associated with the risk of childhood acute leukemia (AL). Folic Acid 61-67 thymidylate synthetase Homo sapiens 234-236 22307944-1 2012 Thymidylate synthase (TS) is an important enzyme involved in folate metabolism and catalyzes methylation of deoxyuridine monophosphate to deoxythymidine monophosphate, which is essential for DNA replication. Folic Acid 61-67 thymidylate synthetase Homo sapiens 0-20 22307944-1 2012 Thymidylate synthase (TS) is an important enzyme involved in folate metabolism and catalyzes methylation of deoxyuridine monophosphate to deoxythymidine monophosphate, which is essential for DNA replication. Folic Acid 61-67 thymidylate synthetase Homo sapiens 22-24 22537194-3 2012 Pemetrexed (Alimta , MTA) is a multitarget antifolate that inhibits folate-dependent enzymes: thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyltransferase, required for de novo synthesis of nucleotides for DNA replication. Folic Acid 47-53 thymidylate synthetase Homo sapiens 94-114 22576918-1 2012 Thymidylate synthase (TS) is a crucial enzyme in folate metabolism and plays a vital role in DNA synthesis and repair. Folic Acid 50-56 thymidylate synthetase Homo sapiens 22-24 22023442-3 2011 Within the parasite, folates are reduced by a bifunctional DHFR (dihydrofolate reductase)-TS (thymidylate synthase) and by a novel PTR1 (pteridine reductase 1), which reduces both folates and unconjugated pteridines. Folic Acid 21-28 thymidylate synthetase Homo sapiens 94-114 21848426-1 2012 Two important polymorphisms of folate cycle enzymes, methylenetetrahydrofolate reductase (MTHFR) C677T and thymidylate synthase (TS) enhancer region (TSER) 28-bp tandem repeat, are related to risk of various types of cancer, including brain tumors, although there are few studies on this subject. Folic Acid 31-37 thymidylate synthetase Homo sapiens 107-127 21848426-1 2012 Two important polymorphisms of folate cycle enzymes, methylenetetrahydrofolate reductase (MTHFR) C677T and thymidylate synthase (TS) enhancer region (TSER) 28-bp tandem repeat, are related to risk of various types of cancer, including brain tumors, although there are few studies on this subject. Folic Acid 31-37 thymidylate synthetase Homo sapiens 129-131 20177420-4 2011 5-FU targets folate metabolism through inhibition of thymidylate synthase (TYMS). Folic Acid 13-19 thymidylate synthetase Homo sapiens 53-73 20177420-4 2011 5-FU targets folate metabolism through inhibition of thymidylate synthase (TYMS). Folic Acid 13-19 thymidylate synthetase Homo sapiens 75-79 21748308-7 2011 Levels of maternal folate intake modified associations with SNPs in CBS, MTRR, and TYMS. Folic Acid 19-25 thymidylate synthetase Homo sapiens 83-87 22023442-3 2011 Within the parasite, folates are reduced by a bifunctional DHFR (dihydrofolate reductase)-TS (thymidylate synthase) and by a novel PTR1 (pteridine reductase 1), which reduces both folates and unconjugated pteridines. Folic Acid 180-187 thymidylate synthetase Homo sapiens 94-114 21301589-2 2010 Antifolates are inhibitors of key enzymes in folate metabolism, namely dihydrofolate reductase, beta-glycinamide ribonucleotide transformylase, 5"-amino-4"-imidazolecarboxamide ribonucleotide transformylase, and thymidylate synthetase. Folic Acid 4-10 thymidylate synthetase Homo sapiens 212-234 21159649-1 2010 The chemotherapeutic drug pemetrexed, an inhibitor of thymidylate synthase, has an important secondary target in human leukemic cells, aminoimidazolecarboxamide ribonucleotide formyltransferase (AICART), the second folate-dependent enzyme of purine biosynthesis. Folic Acid 215-221 thymidylate synthetase Homo sapiens 54-74 21472308-2 2010 The enzymes 5,10-methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) are essential participants in folic acid metabolism and DNA synthesis. Folic Acid 121-131 thymidylate synthetase Homo sapiens 65-85 21472308-2 2010 The enzymes 5,10-methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) are essential participants in folic acid metabolism and DNA synthesis. Folic Acid 121-131 thymidylate synthetase Homo sapiens 87-89 19998340-1 2010 As a key enzyme in folate metabolism, the thymidylate synthase (TS) is important for the synthesis of nucleotides. Folic Acid 19-25 thymidylate synthetase Homo sapiens 42-62 19998340-1 2010 As a key enzyme in folate metabolism, the thymidylate synthase (TS) is important for the synthesis of nucleotides. Folic Acid 19-25 thymidylate synthetase Homo sapiens 64-66 19839928-1 2010 Pemetrexed is a multi-targeted anti metabolite that inhibits several key folate-dependent enzymes in the thymidine and purine biosynthetic pathways, including thymidylate synthase. Folic Acid 73-79 thymidylate synthetase Homo sapiens 159-179 20544798-10 2010 In African Americans, folate derivative levels were associated with smoking, B(12), and polymorphisms in MTR, TYMS, methionine synthase reductase (MTRR), and reduced folate carrier1 (RFC1). Folic Acid 22-28 thymidylate synthetase Homo sapiens 110-114 20544798-11 2010 In Caucasians, folate derivative levels were associated with vitamin use, B(12), and polymorphisms in MTHFR, TYMS, and RFC1. Folic Acid 15-21 thymidylate synthetase Homo sapiens 109-113 19360465-3 2010 Of the analyzed genes, ERCC2, XRCC1, XRCC2, XRCC3 and Lig4 participate in DNA repair, TP53 in cell cycle check point control, AIB1, AR, COMT, CYP11A1, CYP17A1, CYP19A1, HSD17 and PGR in steroid hormone biosynthesis/metabolism/signaling, TYMS in folate metabolism and HER2, IL6, LRP1, TGFB and TGFBR1 affect cell growth. Folic Acid 245-251 thymidylate synthetase Homo sapiens 237-241 20571234-2 2010 The target enzyme for 5- Fluorouracil is thymidylate synthase (TYMS) this enzyme is also involved in folate metabolism. Folic Acid 101-107 thymidylate synthetase Homo sapiens 41-61 20571234-2 2010 The target enzyme for 5- Fluorouracil is thymidylate synthase (TYMS) this enzyme is also involved in folate metabolism. Folic Acid 101-107 thymidylate synthetase Homo sapiens 63-67 19839929-3 2010 Polyglutamate derivatives mainly inhibit three key enzymes of intracellular folate metabolism, i.e. thymidylates synthase (TYMS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), with TYMS being the most relevant target. Folic Acid 76-82 thymidylate synthetase Homo sapiens 100-121 19839929-3 2010 Polyglutamate derivatives mainly inhibit three key enzymes of intracellular folate metabolism, i.e. thymidylates synthase (TYMS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), with TYMS being the most relevant target. Folic Acid 76-82 thymidylate synthetase Homo sapiens 123-127 19839929-3 2010 Polyglutamate derivatives mainly inhibit three key enzymes of intracellular folate metabolism, i.e. thymidylates synthase (TYMS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), with TYMS being the most relevant target. Folic Acid 76-82 thymidylate synthetase Homo sapiens 225-229 19374805-2 2009 TS is the target enzyme of 5-fluorouracil (5-FU) and involved in folate metabolism. Folic Acid 65-71 thymidylate synthetase Homo sapiens 0-2 21209714-2 2010 One of these forms, 5,10 methylenetetrahydrofolic acid (CH(2)THF), is the key one-carbon donor and reduced folate substrate for thymidylate synthase (TS). Folic Acid 107-113 thymidylate synthetase Homo sapiens 128-148 19174154-7 2009 In contrast, each weakly inhibits other enzymes of folate metabolism relevant to rheumatoid arthritis therapy (thymidylate synthase (EC 2.1.1.45), two formyltransferases of purine biosynthesis (EC 2.1.2.2 and EC 2.1.2.3), and 5,10-methylenetetrahydrofolate reductase (EC 1.5.1.20)). Folic Acid 51-57 thymidylate synthetase Homo sapiens 111-131 18851711-1 2009 In contrast with most species, including humans, which have monofunctional forms of the folate biosynthetic enzymes TS (thymidylate synthase) and DHFR (dihydrofolate reductase), several pathogenic protozoal parasites, including Cryptosporidium hominis, contain a bifunctional form of the enzymes on a single polypeptide chain having both catalytic activities. Folic Acid 88-94 thymidylate synthetase Homo sapiens 120-140 18669903-2 2008 We hypothesized that if folate pathway inhibition is the mechanism of cancer preventive activities of EGCG, then the protective effect against breast cancer would be stronger among women with low dietary folate intake and the high-activity methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) genotypes. Folic Acid 24-30 thymidylate synthetase Homo sapiens 288-308 18669903-2 2008 We hypothesized that if folate pathway inhibition is the mechanism of cancer preventive activities of EGCG, then the protective effect against breast cancer would be stronger among women with low dietary folate intake and the high-activity methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TYMS) genotypes. Folic Acid 24-30 thymidylate synthetase Homo sapiens 310-314 18406541-2 2008 Genetic polymorphisms in folate pathway related enzymes including methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, thymidylate synthase (TS) 28-bp tandem repeat, and reduced folate carrier (RFC) G80A have been shown to be associated with increased susceptibility for several cancers. Folic Acid 25-31 thymidylate synthetase Homo sapiens 162-182 18458991-0 2008 Thymidylate synthase genotype and serum concentrations of homocysteine and folate in Behcet"s disease. Folic Acid 75-81 thymidylate synthetase Homo sapiens 0-20 17439323-0 2007 Associations of common polymorphisms in the thymidylate synthase, reduced folate carrier and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine monophosphate cyclohydrolase genes with folate and homocysteine levels and venous thrombosis risk. Folic Acid 202-208 thymidylate synthetase Homo sapiens 44-64 17446168-7 2007 The three folate-dependent enzymes that constitute the de novo thymidylate biosynthesis pathway, cSHMT, thymidylate synthase, and dihydrofolate reductase, all contain SUMO modification consensus sequences. Folic Acid 10-16 thymidylate synthetase Homo sapiens 104-124 17113224-1 2007 Thymidylate synthase and serine hydroxymethyltransferase are involved in folate metabolism. Folic Acid 73-79 thymidylate synthetase Homo sapiens 0-20 17290389-1 2007 Thymidylate synthase (TS) is a key enzyme in folate metabolism, a pathway that is important in colorectal carcinogenesis. Folic Acid 45-51 thymidylate synthetase Homo sapiens 0-20 17290389-1 2007 Thymidylate synthase (TS) is a key enzyme in folate metabolism, a pathway that is important in colorectal carcinogenesis. Folic Acid 45-51 thymidylate synthetase Homo sapiens 22-24 17308042-3 2007 These include (a) its very rapid conversion to active polyglutamate derivatives in cells that build to high levels and are retained for long intervals to achieve prolonged and potent inhibition of its major target enzyme thymidylate synthase, (b) its high affinity for three folate transporters, and (c) its marked sensitivity to the level of physiologic folates in cells. Folic Acid 355-362 thymidylate synthetase Homo sapiens 221-241 17439323-7 2007 However, the TYMS 28-bp repeat was associated with serum and RBC folate levels. Folic Acid 65-71 thymidylate synthetase Homo sapiens 13-17 15930032-2 2005 We hypothesized that the polymorphisms of thymidylate synthase (TYMS) gene involved in folate metabolism are associated with GC risk. Folic Acid 87-93 thymidylate synthetase Homo sapiens 42-62 17684410-3 2007 We found that functional polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS), two key enzymes involved in folate and methyl group metabolism, were significantly associated with increased risk of esophageal squamous cell carcinoma, gastric cardia carcinoma, and pancreatic carcinoma. Folic Acid 61-67 thymidylate synthetase Homo sapiens 90-110 17684410-3 2007 We found that functional polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS), two key enzymes involved in folate and methyl group metabolism, were significantly associated with increased risk of esophageal squamous cell carcinoma, gastric cardia carcinoma, and pancreatic carcinoma. Folic Acid 61-67 thymidylate synthetase Homo sapiens 112-114 16010590-14 2006 The drug interaction may partly be dependent on the folate homeostasis since WiDr/F cells growing at low folate conditions show pronounced synergism in growth inhibition, two-sided TS inhibition and DNA damage, especially when TFT is combined with the tight-binding TS inhibitor GW1843. Folic Acid 105-111 thymidylate synthetase Homo sapiens 181-183 16010590-14 2006 The drug interaction may partly be dependent on the folate homeostasis since WiDr/F cells growing at low folate conditions show pronounced synergism in growth inhibition, two-sided TS inhibition and DNA damage, especially when TFT is combined with the tight-binding TS inhibitor GW1843. Folic Acid 105-111 thymidylate synthetase Homo sapiens 266-268 17201138-1 2006 BACKGROUND: 5,10-Methylenetetrahydrofolate reductase (MTHFR), a key enzyme in folate metabolism, plays a major role in the provision of methyl groups for DNA methylation; thymidylate synthase (TS) is a rate-limiting enzyme in the synthesis of dTMP and DNA repair. Folic Acid 36-42 thymidylate synthetase Homo sapiens 171-191 16723031-3 2006 Thymidylate synthase (TYMS) is a key enzyme that participates in folate metabolism and catalyzes the conversion of dUMP to dTMP in the process of DNA synthesis. Folic Acid 65-71 thymidylate synthetase Homo sapiens 0-20 16723031-3 2006 Thymidylate synthase (TYMS) is a key enzyme that participates in folate metabolism and catalyzes the conversion of dUMP to dTMP in the process of DNA synthesis. Folic Acid 65-71 thymidylate synthetase Homo sapiens 22-26 15930032-2 2005 We hypothesized that the polymorphisms of thymidylate synthase (TYMS) gene involved in folate metabolism are associated with GC risk. Folic Acid 87-93 thymidylate synthetase Homo sapiens 64-68 15579479-2 2005 Thymidylate synthase (TYMS) is involved in the metabolism of folate and the provision of nucleotides needed for DNA synthesis and repair. Folic Acid 61-67 thymidylate synthetase Homo sapiens 0-20 16010439-1 2005 The folate analogue BGC9331 is a new thymidylate synthase (TS) inhibitor showing a broad spectrum of cyto-toxic activity against several human solid tumors, including colorectal cancer. Folic Acid 4-10 thymidylate synthetase Homo sapiens 37-57 16207145-1 2005 Folate metabolism is the target of two major drug groups: folate antagonists (for example, methotrexate) and thymidylate synthase inhibitors (for example, 5-fluorouracil). Folic Acid 0-6 thymidylate synthetase Homo sapiens 109-129 15817609-7 2005 More importantly, a significant interaction between the TS polymorphisms and serum folate status in risk of ESCC and GCA was observed. Folic Acid 83-89 thymidylate synthetase Homo sapiens 56-58 15755837-2 2005 Dihydrofolate reductase (DHFR) is required to convert the folic acid used in supplements and for food fortification and the dihydrofolate produced by thymidylate synthase during DNA synthesis to the reduced folate forms used by the cell. Folic Acid 7-13 thymidylate synthetase Homo sapiens 150-170 15579479-2 2005 Thymidylate synthase (TYMS) is involved in the metabolism of folate and the provision of nucleotides needed for DNA synthesis and repair. Folic Acid 61-67 thymidylate synthetase Homo sapiens 22-26 16045580-1 2005 SUMMARY: Methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) are key enzymes in folate metabolism, which is essential for normal DNA methylation and synthesis. Folic Acid 28-34 thymidylate synthetase Homo sapiens 57-77 16178783-4 2005 Thymidylate synthase (TS or ThyA) has long been considered as one of the best-known drug targets in the anti-cancer area, after which old and new drugs, such as 5-fluoro uracil and the anti-folate ZD1694, have been introduced into chemotherapy to treat solid tumours. Folic Acid 190-196 thymidylate synthetase Homo sapiens 0-20 15510613-2 2004 Functional genetic variants in the methylene tetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) genes may be risk factors for breast cancer because of their central roles in cellular folate metabolism. Folic Acid 55-61 thymidylate synthetase Homo sapiens 106-108 15585623-2 2004 We hypothesized that polymorphisms of the thymidylate synthase (TYMS) gene, which regulates a key enzyme in folate metabolism required for DNA synthesis and repair, are associated with SCCHN risk. Folic Acid 108-114 thymidylate synthetase Homo sapiens 42-62 15585623-2 2004 We hypothesized that polymorphisms of the thymidylate synthase (TYMS) gene, which regulates a key enzyme in folate metabolism required for DNA synthesis and repair, are associated with SCCHN risk. Folic Acid 108-114 thymidylate synthetase Homo sapiens 64-68 15198953-8 2004 The associations of DLCL and FL with TYMS 1494del6 and MTHFR 677TT genotypes, respectively, suggest that folate metabolism may play an important role in the pathogenesis of specific subtypes of NHL. Folic Acid 105-111 thymidylate synthetase Homo sapiens 37-41 15244514-8 2004 The present results suggest that TS polymorphism may modify the risk of esophageal and stomach cancer with smoking, pointing to the necessity for further investigations with information on folate and methionine intake with a larger population. Folic Acid 189-195 thymidylate synthetase Homo sapiens 33-35 15225321-3 2004 We have isolated PAS-resistant transposon mutants of Mycobacterium bovis BCG with insertions in the thymidylate synthase (thyA) gene, a critical determinant of intracellular folate levels. Folic Acid 174-180 thymidylate synthetase Homo sapiens 100-120 15225321-3 2004 We have isolated PAS-resistant transposon mutants of Mycobacterium bovis BCG with insertions in the thymidylate synthase (thyA) gene, a critical determinant of intracellular folate levels. Folic Acid 174-180 thymidylate synthetase Homo sapiens 122-126 15225321-4 2004 BCG thyA mutants have reduced thymidylate synthase activity and are resistant to known inhibitors of the folate pathway. Folic Acid 105-111 thymidylate synthetase Homo sapiens 4-8 15225321-7 2004 Thus, PAS acts in the folate pathway, and thyA mutations probably represent a mechanism of developing resistance not only to PAS but also to other drugs that target folate metabolism. Folic Acid 165-171 thymidylate synthetase Homo sapiens 42-46 15339053-4 2004 Another promising agent is pemetrexed (Alimta), a folate-based inhibitor of thymidylate synthase. Folic Acid 50-56 thymidylate synthetase Homo sapiens 76-96 14745930-1 2003 BACKGROUND: Polymorphisms within the thymidylate synthase (TS) gene that influence enzyme activity may affect plasma folate levels and, indirectly, plasma homocysteine concentrations. Folic Acid 117-123 thymidylate synthetase Homo sapiens 37-57 14676127-2 2003 EXPERIMENTAL DESIGN: Real-time PCR was used to quantify expression levels of folate-associated genes including the reduced folate carrier (RFC-1), folylpolyglutamate synthase (FPGS), gamma-glutamyl hydrolase (GGH),and thymidylate synthase (TS) in tumor tissue and adjacent mucosa of patients with primary colorectal cancer (n=102). Folic Acid 77-83 thymidylate synthetase Homo sapiens 218-238 14745930-1 2003 BACKGROUND: Polymorphisms within the thymidylate synthase (TS) gene that influence enzyme activity may affect plasma folate levels and, indirectly, plasma homocysteine concentrations. Folic Acid 117-123 thymidylate synthetase Homo sapiens 59-61 12839949-2 2003 The nonpolyglutamatable folate-based thymidylate synthase (TS) inhibitor, CB300638 (TS K(i) = 0.24 nM) displayed an IC(50) of 0.0028 microM for the inhibition of the growth of human A431-FBP cells transfected with the alpha-FR. Folic Acid 24-30 thymidylate synthetase Homo sapiens 37-57 14578129-13 2003 Given that individuals with high plasma folate had a better survival outcome with a hazard ratio of 0.68 (0.45-1.03) compared with those with low plasma folate, we conclude that the TS promoter polymorphism may modify both the risk and the survival of CRC; however, these effects do not appear to be mediated through its modulation of biological folate levels. Folic Acid 40-46 thymidylate synthetase Homo sapiens 182-184 14578129-13 2003 Given that individuals with high plasma folate had a better survival outcome with a hazard ratio of 0.68 (0.45-1.03) compared with those with low plasma folate, we conclude that the TS promoter polymorphism may modify both the risk and the survival of CRC; however, these effects do not appear to be mediated through its modulation of biological folate levels. Folic Acid 153-159 thymidylate synthetase Homo sapiens 182-184 14578129-13 2003 Given that individuals with high plasma folate had a better survival outcome with a hazard ratio of 0.68 (0.45-1.03) compared with those with low plasma folate, we conclude that the TS promoter polymorphism may modify both the risk and the survival of CRC; however, these effects do not appear to be mediated through its modulation of biological folate levels. Folic Acid 153-159 thymidylate synthetase Homo sapiens 182-184 12684658-1 2003 Thymidylate synthase (TS), a critical enzyme in the de novo synthesis of thymidylate, is an important target for fluoropyrimidines and folate-based TS inhibitors. Folic Acid 135-141 thymidylate synthetase Homo sapiens 0-20 12684695-2 2003 Thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) are key enzymes in the folate metabolism and both have been shown to be polymorphic affecting the enzyme activity. Folic Acid 49-55 thymidylate synthetase Homo sapiens 22-24 12684658-1 2003 Thymidylate synthase (TS), a critical enzyme in the de novo synthesis of thymidylate, is an important target for fluoropyrimidines and folate-based TS inhibitors. Folic Acid 135-141 thymidylate synthetase Homo sapiens 22-24 12684658-1 2003 Thymidylate synthase (TS), a critical enzyme in the de novo synthesis of thymidylate, is an important target for fluoropyrimidines and folate-based TS inhibitors. Folic Acid 135-141 thymidylate synthetase Homo sapiens 148-150 12084459-1 2002 Studies from our laboratory have shown that the folate-dependent enzyme, thymidylate synthase (TS), functions as an RNA binding protein. Folic Acid 48-54 thymidylate synthetase Homo sapiens 73-93 14529544-14 2003 Thus in rational design and in structure-based design studies, two new classes of antifolate enzyme inhibitors were elaborated-direct inhibitors of thymidylate synthase (TMPS) and direct inhibitors of one or both of the two folate-dependent enzymes of de novo purine synthesis. Folic Acid 86-92 thymidylate synthetase Homo sapiens 148-168 12215845-0 2002 Thymidylate synthase: a novel genetic determinant of plasma homocysteine and folate levels. Folic Acid 77-83 thymidylate synthetase Homo sapiens 0-20 12215845-2 2002 We have investigated the relationship between TYMS genotype and plasma concentrations of homocysteine and folate in a cohort of 505 Chinese from Singapore. Folic Acid 106-112 thymidylate synthetase Homo sapiens 46-50 12215845-3 2002 TYMS 3/3 genotype was associated with reduced plasma folate and, among individuals with low dietary folate intake, with elevated plasma homocysteine levels. Folic Acid 53-59 thymidylate synthetase Homo sapiens 0-4 12215845-3 2002 TYMS 3/3 genotype was associated with reduced plasma folate and, among individuals with low dietary folate intake, with elevated plasma homocysteine levels. Folic Acid 100-106 thymidylate synthetase Homo sapiens 0-4 12215845-5 2002 Our results suggest that TYMS and MTHFR compete for limiting supplies of folate required for the remethylation of homocysteine. Folic Acid 73-79 thymidylate synthetase Homo sapiens 25-29 12167486-1 2002 Folate based inhibitors of thymidylate synthase (TS) might facilitate binding of 5-fluoro-2"-deoxyuridine-5"-monophosphate (FdUMP) to TS similar to the natural reduced folate 5,10-methylenetetrahydrofolate (CH(2)-H(4)-folate). Folic Acid 0-6 thymidylate synthetase Homo sapiens 27-47 12167486-1 2002 Folate based inhibitors of thymidylate synthase (TS) might facilitate binding of 5-fluoro-2"-deoxyuridine-5"-monophosphate (FdUMP) to TS similar to the natural reduced folate 5,10-methylenetetrahydrofolate (CH(2)-H(4)-folate). Folic Acid 168-174 thymidylate synthetase Homo sapiens 27-47 12084459-1 2002 Studies from our laboratory have shown that the folate-dependent enzyme, thymidylate synthase (TS), functions as an RNA binding protein. Folic Acid 48-54 thymidylate synthetase Homo sapiens 95-97 12084461-2 2002 TS is an important target for chemotherapy; it is inhibited by folate and nucleotide analogs, such as by 5-fluoro-dUMP (FdUMP), the active metabolite of 5-fluorouracil (5FU). Folic Acid 63-69 thymidylate synthetase Homo sapiens 0-2 12067974-1 2002 Thymidylate synthase (TS) is a key enzyme in folate metabolism and the primary target of 5-fluorouracil. Folic Acid 45-51 thymidylate synthetase Homo sapiens 0-20 12067974-1 2002 Thymidylate synthase (TS) is a key enzyme in folate metabolism and the primary target of 5-fluorouracil. Folic Acid 45-51 thymidylate synthetase Homo sapiens 22-24 12449732-1 2002 Raltitrexed (Tomudex), a classical folate antagonist, is a selective inhibitor of thymidylate synthase (TS). Folic Acid 35-41 thymidylate synthetase Homo sapiens 82-102 12449732-1 2002 Raltitrexed (Tomudex), a classical folate antagonist, is a selective inhibitor of thymidylate synthase (TS). Folic Acid 35-41 thymidylate synthetase Homo sapiens 104-106 12450432-1 2001 Thymidylate synthase (TS) is an important target for chemotherapy drugs, such as 5-fluorouracil (5-FU), 5-fluorodeoxyuridine (FUDR), oral 5-FU prodrugs (e.g., uracil/tegafur [UFT], S-1, and capecitabine), and other novel folate-based drugs (e.g., raltitrexed, pemetrexed, and nolatrexed). Folic Acid 221-227 thymidylate synthetase Homo sapiens 0-20 12450432-1 2001 Thymidylate synthase (TS) is an important target for chemotherapy drugs, such as 5-fluorouracil (5-FU), 5-fluorodeoxyuridine (FUDR), oral 5-FU prodrugs (e.g., uracil/tegafur [UFT], S-1, and capecitabine), and other novel folate-based drugs (e.g., raltitrexed, pemetrexed, and nolatrexed). Folic Acid 221-227 thymidylate synthetase Homo sapiens 22-24 12052139-1 2002 Folate metabolism is the target of two major drug groups: folate antagonists (e.g., methotrexate) and thymidylate synthase inhibitors (for example, 5-fluorouracil). Folic Acid 0-6 thymidylate synthetase Homo sapiens 102-122 12023790-8 2002 Pemetrexed, a folate-based inhibitor of thymidylate synthase and other enzymes, is currently under investigation in multiple malignancies. Folic Acid 14-20 thymidylate synthetase Homo sapiens 40-60 11774738-2 2001 The cells acquired resistance to antifolate drug(s) through: (1) impaired drug uptake via the reduced folate carrier, (2) increased activity of the target enzymes[dihydrofolate reductase(DHFR) or thymidylate synthase(TS)] resulted from a concomitant amplification and overexpression of their gene, (3) induction of a variant DHFR with a low affinity for antifolate drug(s) used for the selection of resistance, and (4) defective polyglutamation. Folic Acid 37-43 thymidylate synthetase Homo sapiens 196-216 11325838-1 2001 Plasma levels of folates and thymidine in mice are about 10-fold higher than in humans and may influence the therapeutic efficacy of thymidylate synthase (TS) inhibitors, such as 5-fluorouracil (5FU) and the antifolates pemetrexed (MTA) and raltitrexed (RTX). Folic Acid 17-24 thymidylate synthetase Homo sapiens 133-153 11509884-2 2001 Among them, dihydrofolate reductase (DHFR) and thymidylate synthase (TS) require folate as coenzymes. Folic Acid 19-25 thymidylate synthetase Homo sapiens 47-67 11509884-2 2001 Among them, dihydrofolate reductase (DHFR) and thymidylate synthase (TS) require folate as coenzymes. Folic Acid 19-25 thymidylate synthetase Homo sapiens 69-71 11509884-4 2001 Polyglutamated folates are selectively retained within the cell and have an increased affinity for DHFR and TS. Folic Acid 15-22 thymidylate synthetase Homo sapiens 108-110 11524555-2 2001 Pemetrexed inhibits multiple folate-dependent enzymes involved in both purine and pyrimidine synthesis including thymidylate synthase, dihydrofolate reductase, glycinamide ribonucleotide formyltransferase, and aminoimidazole carboxamide ribonucleotide formyltransferase. Folic Acid 29-35 thymidylate synthetase Homo sapiens 113-133 11034814-6 2000 The new fluoro-pyrimidines and TS inhibitors are important classes of drug which have been designed to take advantage of the knowledge of folate metabolism gained from basic clinical research. Folic Acid 138-144 thymidylate synthetase Homo sapiens 31-33