ライフサイエンスコーパス: SCH66336

1 that Ras effector pathways are inhibited by SCH66336.

2 c resolution of a series of intermediates of SCH66336 (1), by either enzymatic acylation of the penda

3 SCH66336, a farnesyl transferase inhibitor in developmen

4 protein synthesis, as early as 3 hours after SCH66336 administration.

5 eEF2K, also occurred at least 12 hours after SCH66336 administration.

6 Treatment with SCH66336 also induced near-complete regression of papill

7 dy, we investigated the molecular effects of SCH66336, an FTI, in head and neck squamous cell carcino

8 ate binding site of Pgp, a quality unique to SCH66336 and its analogues, although not inherent to far

9 Here we report that combination therapy with SCH66336 and SCH58500 has synergistic or additive antipr

10 Greater combined efficacy for SCH66336 and SCH58500 was also observed in vivo in the D

11 arnesyltransferase inhibitors--the tricyclic SCH66336 and the methylquinolone R115777--as single agen

12 and fatigue were dose-limiting at 400 mg of SCH66336 b.i.d.

13 The FTI SCH66336 blocks HRAS farnesylation and delocalizes it fr

14 A further benefit of coadministration of SCH66336 could be reduced chemotherapy dosage, hence, lo

15 ines harboring HRAS, NRAS or KRAS mutations, SCH66336 delocalized, inhibited signaling and preferenti

16 SCH66336 did not inhibit S6 phosphorylation in cells exp

17 This observation indicates that SCH66336 directly interacts with the substrate binding s

18 lid tumors received 92 courses of escalating SCH66336 doses given orally twice a day (b.i.d.) for 7 d

19 ntly, expression of Rheb-CSVL also abrogated SCH66336 enhancement of tamoxifen- and docetaxel-induced

20 alternative prenylation, and plays a role in SCH66336 enhancement of the anti-tumor response to other

21 Moreover, SCH66336 enhances STI571-induced apoptosis in STI571-sen

22 Moreover, low concentrations of SCH66336 exhibit synergy with the Pgp substrate/inhibito

23 The farnesyltransferase inhibitor SCH66336 exhibits antitumor activity in vitro and in viv

24 effect of the farnesyl transferase inhibitor SCH66336 in an in vivo murine model of Bcr/Abl-positive

25 or combination clinical trials of STI571 and SCH66336 in CML patients and suggest that combination th

26 toxicities, and biological effectiveness of SCH66336 in inhibiting FT in vivo.

27 in cell culture was completely inhibited by SCH66336, indicating a lack of alternative prenylation.

28 We showed that SCH66336 induced phosphorylation (inactivation) of eukar

29 tively active form of Akt rescued cells from SCH66336-induced apoptosis.

30 SCH66336 inhibits farnesylation of RAS and other protein

31 h SCH66336 was demonstrated, confirming that SCH66336 inhibits protein farnesylation in vivo.

32 SCH66336 is a p.o.-active, farnesyl protein transferase

33 These results suggest that SCH66336 is a potent apoptosis inducer in HNSCC cells an

34 conclude that farnesyl transferase inhibitor SCH66336 is able to revert early signs of leukemia and s

35 SCH66336 is one of the first FT inhibitors to undergo cl

36 Lonafarnib (SCH66336) is a farnesyl transferase inhibitor (FTI) that

37 hat the farnesyl transferase inhibitor (FTI) SCH66336 (lonafarnib) inhibits the proliferation of STI5

38 on stroma and made them resistant to the FTI SCH66336/lonafarnib to model emerging drug resistance in

39 inactivation of eEF2 is a novel mechanism of SCH66336-mediated growth inhibition and that this effect

40 rine cell line that is leukemogenic in mice, SCH66336 potently inhibited soft agar colony formation,

41 analysis of BCR/ABL-BaF3 cells treated with SCH66336 revealed G2/M blockade, consistent with recent

42 he efficacy of the three-drug combination of SCH66336, SCH58500, and paclitaxel was also examined in

43 Furthermore, SCH66336 selectively inhibited the hematopoietic colony

44 that of ABL tyrosine kinase inhibition, FTI SCH66336 shows promise for the treatment of BCR/ABL-indu

45 SCH66336 significantly inhibited daunorubicin transport

46 We found that SCH66336 suppressed growth and induced apoptosis of huma

47 SCH66336 suppressed protein kinase B/Akt activity as wel

48 In contrast, nearly all mice treated with SCH66336 survived and have remained disease-free for mor

49 SCH66336 treatment also inhibited the phosphorylation of

50 es eEF2, was observed only at 12 hours after SCH66336 treatment.

51 he current study, the clinical candidate FTI SCH66336 was characterized for its ability to inhibit BC

52 buccal mucosa cells of patients treated with SCH66336 was demonstrated, confirming that SCH66336 inhi

53 However, SCH66336 was more inhibitory than dominant-negative Ras

54 Additionally, by an ATP-hydrolysis assay, SCH66336 was shown to decrease Pgp-mediated ATP hydrolys

55 he farnesyltransferase inhibitor lonafarnib (SCH66336) was conducted in children with recurrent or pr

56 e provided protection against the effects of SCH66336, whereas knockdown of endogenous ATP11a using s

57 mbining a Ras pathway inhibitor (lonafarnib, SCH66336) with a proteasome inhibitor (bortezomib, Velca

58 Treatment with SCH66336 would be predicted to be synergistic with coadm