ライフサイエンスコーパス: discodermolide

1 ers of the tubulin-polymerizing molecule (+)-discodermolide.

2 hort microtubules similar to those formed by discodermolide.

3 nts, which assembled the carbon framework of discodermolide.

4 ictyostatin's close structural congener, (+)-discodermolide.

5 e template for the bioactive conformation of discodermolide.

6 ot differ greatly from that of paclitaxel or discodermolide.

7 of C(1)-C(8) and C(15)-C(21) subunits of (+)-discodermolide.

8 and 6c both showed properties unique to (+)-discodermolide.

9 ucts, eleutherobin, epothilones A and B, and discodermolide.

10 ides retained nearly complete sensitivity to discodermolide.

11 e paclitaxel side chain is unoccupied by (+)-discodermolide.

12 practical stereocontrolled synthesis of (+)-discodermolide (1) has been completed in 10.3% overall y

13 l lines, retained significant sensitivity to discodermolide (25- and 89-fold more resistant relative

14 er-assisted structure analysis indicated (+)-discodermolide, a polyhydroxylated alkatetraene lactone

15 el total synthesis of the complex polyketide discodermolide, a promising anticancer agent of marine s

16 otal synthesis of the complex polyketide (+)-discodermolide, a promising anticancer agent of sponge o

17 Discodermolide also has unique properties that distingui

18 In the present study, photoaffinity-labeled discodermolide analogues are used to investigate their b

19 approximately 1%, of the three radiolabeled discodermolide analogues explored.

20 Three photoaffinity-labeled discodermolide analogues were synthesized, all of which

21 preparation of gram-scale quantities of (+)-discodermolide and analogues.

22 Although less potent than (+)-discodermolide and paclitaxel, compounds 6b and 6c both

23 onataxel, the epothilones, eleutherobin, and discodermolide, and rationalizes the extensive structure

24 merization assay, it was more cytotoxic than discodermolide, and, like discodermolide, demonstrated s

25 f the cell cycle, and we have now found that discodermolide arrests Burkitt lymphoma cells in mitosis

26 Potential binding modes of (+)-discodermolide at the paclitaxel binding site of tubulin

27 rmolide can effectively displace C19-[3H]BPC-discodermolide binding.

28 axol cannot effectively displace C19-[3H]BPC-discodermolide binding.

29 p-N and Arg-C enzymes suggested that C19-BPC-discodermolide binds to amino acid residues, 355-359, in

30 We confirmed that, like Taxol, discodermolide binds to the taxane binding pocket in bet

31 e, C19-[4-(4-(3)H-benzoyl-phenyl)-carbamate]-discodermolide (C19-[3H]BPC-discodermolide), was selecte

32 Similar to discodermolide, C19-BPC-discodermolide can effectively d

33 Although compared to discodermolide, C19-BPC-discodermolide revealed no hyper

34 Similar to discodermolide, C19-BPC-discodermolide can effectively displace [3H]Taxol from m

35 Discodermolide can effectively displace C19-[3H]BPC-disc

36 oup and the C14 and C16 methyl groups of (+)-discodermolide could be deleted without undermining acti

37 The natural product (+)-discodermolide (DDM) is a microtubule stabilizing agent

38 (+)-Discodermolide (DDM), a polyketide macrolide from marine

39 ore cytotoxic than discodermolide, and, like discodermolide, demonstrated synergism with Taxol.

40 Like discodermolide, dictyostatin retained antiproliferative

41 id site agents [paclitaxel, epothilones A/B, discodermolide, dictyostatin, eleutherobin, the steroid

42 A new synthesis of discodermolide employs a previously undisclosed stereose

43 rotubule stabilizing agents, epothilone D or discodermolide, followed by dosing with 1-aminoanthracen

44 e effective than taxol in inducing assembly, discodermolide had an EC50 value of 3.2 microM versus 23

45 Discodermolide had equally impressive effects on tubulin

46 ther compound examined, and dictyostatin and discodermolide had equivalent activity as inhibitors of

47 convergent stereocontrolled synthesis of (+)-discodermolide has been achieved with 2.1% overall yield

48 led to a putative binding model for C19-BPC-discodermolide in tubulin.

49 istance to discodermolide via restoration of discodermolide-induced accelerated senescence.

50 propose a role for 4E-BP1 as a regulator of discodermolide-induced accelerated senescence.

51 Discodermolide-induced polymer differed from taxol-induc

52 lly expressed mRNAs implicated in overcoming discodermolide-induced senescence.

53 Furthermore, we demonstrated that discodermolide is a competitive inhibitor with [3H]pacli

54 Discodermolide is a microtubule-stabilizing agent that i

55 Discodermolide is a potentially important antitumor agen

56 crotubule-stabilizing, antimitotic agent (+)-discodermolide is described.

57 similar to those of paclitaxel (Taxol), but discodermolide is more potent.

58 s suggest that the hypernucleation effect of discodermolide is not involved in its cytotoxic activity

59 d subtilisin digestion indicate that C19-BPC-discodermolide labels amino acid residues 305-433 in bet

60 n on the conformational effects of Taxol and discodermolide on microtubules isolated from chicken ery

61 mplementary stabilizing effects of Taxol and discodermolide on the microtubules, which may explain th

62 The effects of discodermolide on the reorganization of the microtubules

63 hich has major interactions with the M-loop, discodermolide orients itself away from this loop and to

64 ed on these findings, a small library of (+)-discodermolide-paclitaxel hybrids have been designed and

65 support continued preclinical development of discodermolide, particularly in the chemorefractory sett

66 ng agents including Taxol, epothilone B, and discodermolide produce aneuploid populations of A549 cel

67 Furthermore, this synthesis of discodermolide provides the first examples of the asymme

68 ubule rearrangement that occurred with 10 nM discodermolide required 1 microM taxol.

69 A discodermolide-resistant cell line, AD32, was generated

70 Although compared to discodermolide, C19-BPC-discodermolide revealed no hypernucleation effect in the

71 ariations in the right and left sides of the discodermolide scaffold revealed additional structure/ac

72 1 mRNA and protein, relative to the parental discodermolide-sensitive A549 cells.

73 Additionally, discodermolide stabilizes microtubules mainly via its ef

74 common building block, corresponding to the discodermolide stereotriad.

75 cal concentrations and shorter polymers with discodermolide than paclitaxel under a variety of reacti

76 tubulin assembly was also more vigorous with discodermolide than with taxol under every reaction cond

77 parison of the abilities of dictyostatin and discodermolide to induce tubulin assembly demonstrated t

78 statin inhibited the binding of radiolabeled discodermolide to microtubules more potently than any ot

79 Discodermolide-treated breast carcinoma cells displayed

80 Previous work had shown an accumulation of discodermolide-treated cells in the G2/M portion of the

81 in interphase cells much more rapidly after discodermolide treatment compared with paclitaxel treatm

82 roliferation rate and reverted resistance to discodermolide via restoration of discodermolide-induced

83 ng agents, including taxotere, epothilone B, discodermolide, vincristine, 2-methoxyestradiol, and col

84 stent with this, cell growth and response to discodermolide was confirmed in vivo using tumor xenogra

85 The marine natural product (+)-discodermolide was first isolated in 1990 and, to this d

86 enyl)-carbamate]-discodermolide (C19-[3H]BPC-discodermolide), was selected for photolabeling studies

87 Several novel analogues of (+)-discodermolide were synthesized via a convergent strateg

88 of diastereomers and structural analogues of discodermolide, which should serve as valuable probes fo

89 ne-bearing polyhydroxylated alkatetraene (+)-discodermolide, which was isolated from the sponge Disco

90 en erythrocyte tubulin (CET) of another MSA, discodermolide, whose synthetic analogues may have poten