ライフサイエンスコーパス: discodermolide

1 hort microtubules similar to those formed by discodermolide.

2 nts, which assembled the carbon framework of discodermolide.

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

4 e template for the bioactive conformation of discodermolide.

5 ot differ greatly from that of paclitaxel or discodermolide.

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

7 e paclitaxel side chain is unoccupied by (+)-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 practical stereocontrolled synthesis of (+)-discodermolide (1) has been completed in 10.3% overall y

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

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

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

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

16 Discodermolide also has unique properties that distingui

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

38 Like discodermolide, dictyostatin retained antiproliferative

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

40 A new synthesis of discodermolide employs a previously undisclosed stereose

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

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

43 Discodermolide had equally impressive effects on tubulin

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

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

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

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

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

49 Discodermolide-induced polymer differed from taxol-induc

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

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

52 Discodermolide is a microtubule-stabilizing agent that i

53 Discodermolide is a potentially important antitumor agen

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

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

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

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

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

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

60 The effects of discodermolide on the reorganization of the microtubules

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

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

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

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

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

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

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

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

69 1 mRNA and protein, relative to the parental discodermolide-sensitive A549 cells.

70 Additionally, discodermolide stabilizes microtubules mainly via its ef

71 common building block, corresponding to the discodermolide stereotriad.

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

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

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

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

76 Discodermolide-treated breast carcinoma cells displayed

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

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

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

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

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

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

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

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

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

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

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