ライフサイエンスコーパス: ET-743

1 olecular basis for the antitumor activity of Et 743.

2 ced the differentiation process initiated by ET-743.

3 We also explored the method of action of ET-743.

4 adipocytic differentiation-based response to ET-743.

5 Ecteinascidin 743 (ET-743), a highly promising marine-based antitumor agent

6 We also found that ET-743, a potent antineoplastic agent, suppressed MDR1 t

7 t physiologically relevant concentrations of ET-743 abrogate transcriptional activation of both the e

8 onal changes in the DNA than the more stable Et 743-AGC adduct.

9 lectrophoresis and (1)H NMR experiments, the Et 743-AGT adduct is less stable, has more dynamic motio

10 Et 743 alkylates guanine N2 through the minor groove of

11 It was previously shown that ET-743, an antitumor compound with an unclear mechanism

12 etween the structural modification of DNA by Et 743 and its biological potency and efficacy in tumor

13 assess the nature of the interaction between ET-743 and other antineoplastic agents using the combina

14 hese results suggest that the combination of ET-743 and paclitaxel should be assessed in clinical tri

15 the transcriptional inhibition of COL1A1 by ET-743 are not apparent, our observations suggest that t

16 gene by Trichostatin A (TSA) was blocked by ET-743 at concentrations that had minimal effect on unin

17 Surprisingly, we find that Et 743 bends DNA toward the major groove, which is a uni

18 Et 743 binds in the minor groove of DNA and alkylates N2

19 Moreover, ET-743 blocked induction of Gal4 fusion proteins by TSA

20 of the reversible nature of Et 743 with DNA, Et 743 can migrate from the nonfavored bonding sequence

21 We examined the cytotoxic effect of ET-743 combined with six other antineoplastic agents on

22 In the present study, we tested whether ET-743 could block activation of the MDR1 promoter by ag

23 ET-743 demonstrates clinical activity as first-line ther

24 Furthermore, ET-743 did not affect the binding of CBF or Sp1 transcri

25 ise from differences in the stability of the Et 743-DNA adduct at the 5'-AGT and 5'-AGC target sequen

26 both the reactivity and the stability of the Et 743-DNA adduct.

27 The shuffling of Et 743-DNA adducts to the more stable alkylation sites h

28 ET-743 downregulated TLS:CHOP expression, which correlat

29 nto SSc cells previously treated with 700 pM ET-743 failed to show an effect on COL1A1 promoter activ

30 ction and definitively establish the role of ET-743 for patients with these malignancies.

31 Patients were treated with 1.5 mg/m2 of ET-743 given as a 24-hour continuous intravenous (IV) in

32 h exhibits poor activity in cellular assays, Et 743 has shown good efficacy as an antitumor agent.

33 he marine natural product ecteinascidin 743 (Et 743) has been prepared and evaluated as antitumor age

34 ential treatment with paclitaxel followed by ET-743 increased the antitumor effects in nude mice bear

35 lysis of SW620 cells treated with TSA and/or ET-743 indicated that activation of TSA-responsive promo

36 Phthalascidin and Et 743 induce DNA-protein cross-linking and, although th

37 d to examine the extent and direction of the Et 743-induced bend.

38 Of the numerous Ets isolated, Et 743 is presently being evaluated in phase II clinical

39 ranscription factor (NF-Y), we now show that ET-743 is a more general inhibitor of activated transcri

40 rts, leads us to suggest a mechanism whereby ET-743 is a novel, potent, and general inhibitor of acti

41 These results indicate that ET-743 is a potent inhibitor of COL1A1 transcription.

42 ET-743 is a promising new option for the management of s

43 ET-743 is therefore the prototype for a distinct class o

44 Ecteinascidin 743 (ET-743) is a chemotherapeutic agent that binds with sequ

45 Ecteinascidin 743 (ET-743) is a potent antitumor agent from the Caribbean t

46 Ecteinascidin-743 (ET-743) is a promising chemotherapeutic agent currently

47 concentration and total plasma clearance of ET-743 (mean +/- standard deviation), 1.04 +/- 0.48 ng/m

48 of Chou and Talalay to better understand how ET-743 might be used clinically.

49 However, treatment with 700 pM ET-743 of stably transfected NIH 3T3 cells expressing a

50 Therefore, we examined the effects of ET-743 on the increased COL1A1 expression in SSc fibrobl

51 Ecteinascidin 743 (Et 743), one of a series of structurally related antitum

52 lop rational treatment combinations, such as ET-743 plus PPARgamma agonists, for the treatment of MRC

53 ced and assembled the complete genome of the ET-743 producer, Candidatus Endoecteinascidia frumentens

54 s also greatly expanded our understanding of ET-743 production and revealed new biosynthetic genes di

55 Phthalascidin and Et 743 show undiminished potency in camptothecin- and et

56 ion that dictate the sequence selectivity of Et 743 toward its favored target sequence.

57 Pretreatment with paclitaxel for 24 h before ET-743 was the most effective combination regimen in all

58 study, DNA structural distortions induced by Et 743 were examined to provide insight into the molecul

59 ore readily synthesized and more stable than Et 743, which is currently undergoing clinical trials.

60 Here, we report that the reaction of Et 743 with DNA is reversible under nondenaturing condit

61 rect consequence of the reversible nature of Et 743 with DNA, Et 743 can migrate from the nonfavored

62 of these, phthalascidin, is very similar to Et 743 with regard to in vitro potency and mode of actio

63 n of TSA-responsive promoters was blocked by ET-743 with little affect on nonresponsive promoters.

64 Ecteinascidin 743 (ET-743, Yondelis) is a clinically approved chemotherapeu