ライフサイエンスコーパス: FdUMP

1 FdUMP inhibits thymidylate synthase and causes the accum

2 FdUMP shows a similar profile, while dGMP does not alter

3 FdUMP[10] exhibits more potent antiproliferative activit

4 FdUMP[10] induces DNA single-strand breaks and cellular

5 FdUMP[10] inhibited thymidylate synthase (TS) and trappe

6 FdUMP[10] remained effective against cells expressing th

7 FdUMP[10] was better tolerated than 5-FU or cytarabine p

8 FdUMP[10], a 10mer of 5-fluoro-2'-deoxyuridine 5'-monoph

9 ecipitate, and the resultant Ca(3)(PO(4))(2)*FdUMP nanoprecipitate is encapsulated into the AEAA-targ

10 +)[BMP](2-)) and antitumor agents ([ZrO](2+)[FdUMP](2-)) with an up to 80% load of active drug is pos

11 s and by ternary complex formation with [32P]FdUMP and 5,10-methylenetetrahydrofolate.

12 In order to create 5-FdUMP resistant enzymes to protect chemosensitive normal

13 is metabolized to 5-fluorodeoxyuridylate (5-FdUMP), a tight binding covalent inhibitor of thymidylat

14 dUMP)/deoxy-5-fluorouridine monophosphate (5-FdUMP) as a substrate.

15 cells and further understand mechanisms of 5-FdUMP resistance, we have randomized four residues withi

16 This 5-FdUMP-resistant mutant, or others similarly selected, is

17 noformulation (termed Nano-FdUMP) containing FdUMP (5-Fu active metabolite) was newly developed using

18 based inhibitor, 5-fluoro-2'-deoxyuridylate (FdUMP), into a ternary complex.

19 the mechanism-based inhibitor 5-fluoro-dUMP (FdUMP) and methylenetetrahydrofolate (CH2THF) have been

20 esent, in addition to the nucleotides (dUMP, FdUMP, or dGMP), a Td of 72 degrees C is achieved and th

21 The stabilization of dUMP, FdUMP, and dGMP binding to Escherichia coli thymidylate

22 The folic acid conjugate FA-FdUMP[10] showed improved cytotoxicity toward human colo

23 Enhanced cytotoxicity was observed for FA-FdUMP[10] relative to nonconjugated FdUMP[10] for cells

24 Thus, FA-FdUMP[N] may prove useful for the treatment of 5-FU-resi

25 Second, for Nano-FdUMP, FdUMP (the active metabolite of 5-Fu) is entrapped insid

26 y complex of TS with 5-fluorodeoxyuridylate (FdUMP) and 5, 10-methylenetetrahydrofolylpolyglutamate w

27 The novel fluoropyrimidine, FdUMP[10], was highly active against both human AML cell

28 eveloped a novel class of fluoropyrimidines, FdUMP[N], that are oligodeoxynucleotides (ODNs) composed

29 rate that the dissociation constant (Kd) for FdUMP binding into the ternary complex was 20-fold highe

30 exposed to IFN-alpha + gamma and FUra, free FdUMP levels became detectable, whereas [3H]FUra-RNA inc

31 ilibrium binding studies with the inhibitor, FdUMP, demonstrate that the dissociation constant (Kd) f

32 y respects: (i) the methylene bridge linking FdUMP and CH2THF is rotated about 60 degrees to a differ

33 d between TS protein and the FdU metabolite, FdUMP.

34 de 5-fluoro-2'-deoxyuridine-5'monophosphate (FdUMP).

35 f 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) is added to growing DM-transformed cells, the com

36 f 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP), the thymidylate synthase inhibitory metabolite o

37 erted to 5-fluorodeoxyuridine monophosphate (FdUMP) and 5-fluorodeoxyuridine triphosphate (FdUTP).

38 5-fluoro-2'-deoxyuridine-5'-O-monphosphate (FdUMP) nucleotides.

39 (containing platinum drug and FnA) and Nano-FdUMP (containing fluorine drug) significantly improves

40 The procedures for Nano-Folox and Nano-FdUMP take ~17 h and ~4 h, respectively (~17 h if they a

41 e (MC) nanoformulations, Nano-Folox and Nano-FdUMP, have recently been developed by using the nanopre

42 In addition, combination of Nano-Folox/Nano-FdUMP and anti-PD-L1 antibody significantly inhibited CR

43 Second, for Nano-FdUMP, FdUMP (the active metabolite of 5-Fu) is entrappe

44 A nanoformulation (termed Nano-FdUMP) containing FdUMP (5-Fu active metabolite) was new

45 It resulted mainly from the fact that Nano-FdUMP mediated the formation of reactive oxygen species

46 d for FA-FdUMP[10] relative to nonconjugated FdUMP[10] for cells grown under folate-restricted condit

47 In all cases, the IC(50) of FdUMP[10] was lower than for cytarabine and approximatel

48 tion and (ii) the electron density for C6 of FdUMP, which is covalently linked to Cys 146, is more di

49 it conjugation of folic acid to the 5'-OH of FdUMP[10] via a phosphodiester linkage using automated s

50 ction involving the intracellular release of FdUMP.

51 g is possible (BMP = betamethason phosphate, FdUMP = 5'-fluoro-2'-deoxyuridine 5'-monophosphate).

52 ovel haloethyl and piperidyl phosphoramidate FdUMP prodrug analogues has been synthesized, and the gr

53 In summary, FdUMP[10] was highly efficacious and better tolerated th

54 more potent antiproliferative activity than FdUMP or 5-fluoro-2'-deoxyuridine (FdU) and is markedly

55 We propose that FdUMP[10] damages DNA by trapping Top1 at uracil and FdU

56 The FdUMP[10]-induced Top1-DNA complexes are not inhibited b

57 e cross-resistant to FdUMP[10] as well as to FdUMP, FdU, and the thymidylate synthase inhibitor ralti

58 sts that <50% of the prodrug is converted to FdUMP intracellularly by this pathway.

59 45 cells lacking Top1 are cross-resistant to FdUMP[10] as well as to FdUMP, FdU, and the thymidylate

60 h complexes are also observed in response to FdUMP, FdU, raltitrexed, and FU.

61 In the crystal structure of a V3F.FdUMP binary complex, the nucleotide is bound in an alte

62 In vivo, FdUMP[10] was active against a syngeneic AML model with

63 Escherichia coli TS in ternary complex with FdUMP and the inhibitor 10-propargyl-5,8-dideazafolic ac

64 , TS protein was altered upon treatment with FdUMP, but 5-FU toxicity seemed to be largely RNA-based,