ライフサイエンスコーパス: adaphostin

1 g bortezomib, lenalidomide, enzastaurin, and adaphostin.

2 species (ROS) in the cytotoxic mechanism of adaphostin.

3 1-resistant K562 cells remained sensitive to adaphostin.

4 observed when intact cells were treated with adaphostin.

5 medium and that the highest concentration of adaphostin (3000-fold over extracellular concentrations)

6 Consistent with a mitochondrial site for adaphostin action, adaphostin-induced ROS production was

7 Adaphostin also caused a decrease in the level of the an

8 Adaphostin also induced cleavage and dephosphorylation o

9 Here we show the antimyeloma cytotoxicity of adaphostin and carried out expression profiling of adaph

10 Interactions between the tyrphostin adaphostin and proteasome inhibitors (eg, MG-132 and bor

11 ells with marginally toxic concentrations of adaphostin and proteasome inhibitors synergistically pot

12 ite-directed agent STI571 and the tyrphostin adaphostin are undergoing evaluation as bcr/abl kinase i

13 Collectively, these results identify adaphostin as a mechanistically distinct CML-selective a

14 Further preclinical development of adaphostin as a novel agent for the treatment of CLL app

15 esults not only outline a mechanism by which adaphostin can damage both myeloid and lymphoid leukemia

16 Further study demonstrated that adaphostin caused intracellular peroxide production foll

17 Exposure of cells to adaphostin concentrations > or =0.75 microM for interval

18 ading of isolated mitochondria to equivalent adaphostin concentrations caused inhibition of uncoupled

19 Adaphostin demonstrated selectivity for CML myeloid prog

20 he potential molecular mechanism(s) by which adaphostin elicits its anti-proliferative effect(s).

21 Moreover, adaphostin enhanced the production of ROS by succinate-c

22 Consistent with these results, 24-hour adaphostin exposure inhibited CML granulocyte colony-for

23 Further analysis demonstrated that adaphostin had no effect on pyruvate or succinate dehydr

24 However, this effect of adaphostin in adherent cells/solid tumor models has not

25 vestigated the anti-proliferative effects of adaphostin in the human prostate cancer cell line PC-3.

26 Adaphostin increased the level of reactive oxygen specie

27 Initial studies demonstrated that adaphostin induced apoptosis in a variety of Bcr/abl- ce

28 Moreover, the combination of STI571 + adaphostin induced more cytotoxicity in K562 cells and i

29 Immunoblots demonstrated adaphostin induced poly(adenosine diphosphate-ribose) po

30 istolated) Akt also significantly attenuated adaphostin-induced apoptosis, but protection was less th

31 We also observed adaphostin-induced c-Abl cleavage in immunoblot analysis

32 sion by small interfering RNA confirmed that adaphostin-induced c-Jun up-regulation triggers downstre

33 istance examined remained fully sensitive to adaphostin-induced cell death.

34 ly active MEK1 construct markedly diminished adaphostin-induced cytochrome c and AIF release, JNK act

35 This adaphostin-induced G(1) arrest was associated with an in

36 ng of the hydroquinone moiety is a source of adaphostin-induced ROS and identify complex III as a pot

37 he antioxidant N-acetylcysteine blocked both adaphostin-induced ROS generation and apoptosis.

38 a mitochondrial site for adaphostin action, adaphostin-induced ROS production was diminished by >75%

39 These findings not only indicate that adaphostin induces apoptosis selectively in CLL B cells

40 age of caspase-3 substrates, suggesting that adaphostin induces apoptosis.

41 ese findings demonstrate that the tyrphostin adaphostin induces multiple perturbations in signal tran

42 Instead, adaphostin inhibited reduced decylubiquinone-induced cyt

43 We demonstrate that adaphostin inhibits the proliferation of PC-3 cells by i

44 Adaphostin is a dihydroquinone derivative that is underg

45 Adaphostin is a tyrphostin that was originally intended

46 Furthermore, we have determined that the adaphostin-mediated cell cycle arrest of PC-3 cells is d

47 fy for the first time a signaling cascade of adaphostin-mediated G(1) phase-specific cell cycle arres

48 ts (e.g., L-N-acetylcysteine; L-NAC) opposed adaphostin-mediated mitochondrial dysfunction, Raf-1/MEK

49 , enforced activation of MEK failed to block adaphostin-mediated ROS generation.

50 wth factor receptor-c-Met is involved in the adaphostin-mediated signaling events that regulate p38 M

51 Adaphostin/MG-132 lethality as well as mitochondrial dam

52 Finally, the adaphostin/MG-132 regimen displayed similar toxicity tow

53 of the JNK pathway significantly diminished adaphostin/MG-132-mediated lethality.

54 f or MEK/ERK activation partially diminished adaphostin/MG-132-mediated ROS generation, suggesting th

55 of the tyrphostin tyrosine kinase inhibitor adaphostin (NSC 680410) have been examined in human leuk

56 Adaphostin (NSC 680410), an analog of the tyrphostin AG9

57 Adaphostin (NSC680410), a small molecule congener of tyr

58 e mode of action, we examined the effects of adaphostin on numerous imatinib-resistant leukemia model

59 y, these data suggest that ROS generation by adaphostin overcomes even the most potent imatinib resis

60 They also suggest that adaphostin-related oxidative stress acts upstream of per

61 staining revealed that the concentration of adaphostin required to induce 50% cell death (IC50) at 2

62 Treatment of K562 cells with 10 microM adaphostin resulted in decreased p210(bcr/abl) polypepti

63 nown chemical properties of dihydroquinones, adaphostin simultaneously underwent oxidation to the cor

64 ty of the investigational antileukemic agent adaphostin to induce apoptosis in CLL B cells and synerg

65 stin and carried out expression profiling of adaphostin-treated multiple myeloma (MM) cells to identi

66 Additionally, we found that adaphostin treatment induced a decrease in the phosphory

67 When adaphostin was combined with fludarabine (F-ARA-AMP), a

68 ance liquid chromatography demonstrated that adaphostin was concentrated by up to 300-fold in cells r

69 he present study, the mechanism of action of adaphostin was investigated in greater detail in vitro.

70 ntiangiogenic activity of our tool compound, adaphostin, was subsequently shown in a zebrafish model

71 t potentiating oxidative damage by combining adaphostin with proteasome inhibitors warrants attention