ライフサイエンスコーパス: UCN-01

1 in human serum, a property not possessed by UCN-01.

2 n inhibitory peptide of NF-kappaB (SN50) and UCN-01.

3 examples include perifosine, lovastatin, and UCN-01.

4 bitor caffeine, or the Chk1 kinase inhibitor UCN-01.

5 nsistent with the potency and selectivity of UCN-01.

6 ediated apoptosis by bryostatin 1 but not by UCN-01.

7 S-phase checkpoint that was dysregulated by UCN-01.

8 re of the Chk1 kinase domain in complex with UCN-01.

9 were inhibited by the Chk1 kinase inhibitor UCN-01.

10 tal salivary concentration was 111 nmol/L of UCN-01.

11 T-ALL cells influences their sensitivity to UCN-01.

12 sphorylated in irradiated cells treated with UCN-01.

13 ial targets of G(2) checkpoint abrogation by UCN-01.

14 piridol displaying more potent activity than UCN-01.

15 rrest in S phase with high concentrations of UCN-01.

16 st in G1 even at very high concentrations of UCN-01.

17 y the structurally distinct radiosensitizer, UCN-01.

18 tment, and this effect was also abrogated by UCN-01.

19 n locus were abrogated by the Chk1 inhibitor UCN-01.

20 e I clinical trial of FU in combination with UCN-01.

21 had no effect on the area under the curve of UCN-01.

22 rwent both S and G(2) phase progression with UCN-01.

23 n combination with once a month infusions of UCN-01.

24 was refractory to the cell cycle effects of UCN-01.

25 transfected cells were 6-7-fold resistant to UCN-01.

26 ys were relevant for the induction of p21 by UCN-01.

27 Flavopiridol (0.1 mcmol/L) and UCN-01 (1 mcmol/L) also induced striking decreases in th

28 ells with a minimally toxic concentration of UCN-01 (150 nM) for 24 hours resulted in mitogen-activat

29 d with either staurosporine (50 nM; 6 hr) or UCN-01 (300 nM; 6 hr) after a 1-hr preincubation, exposu

30 We have reported that UCN-01 (7-hydroxystaurosporine) abrogates DNA damage-ind

31 UCN-01 (7-hydroxystaurosporine) is a cell-cycle checkpoi

32 UCN-01 (7-hydroxystaurosporine) is a potent antitumor ag

33 K inhibitor, LY294002, and an Akt inhibitor, UCN-01 (7-hydroxystaurosporine), both synergistically se

34 UCN-01 (7-hydroxystaurosporine), currently in clinical t

35 e cdk modulator tested in clinical trials is UCN-01 (7-hydroxystaurosporine).

36 G2 arrest was blocked by UCN-01, a CHK1 inhibitor, but proceeded in CHK2 knock-ou

37 UCN-01, a kinase inhibitor that effectively abrogates ch

38 We have previously demonstrated that UCN-01, a potent protein kinase inhibitor currently in p

39 UCN-01, a protein kinase inhibitor currently undergoing

40 Caffeine or UCN-01 abolishes the extreme radioresistance with the st

41 UCN-01 abrogated S and G(2) arrest in the p53 mutant bre

42 The staurosporine analog UCN-01 abrogated this G2 arrest and sensitized the resis

43 of Chk1 kinase with 7-hydroxystaurosporine (UCN-01) abrogated the checkpoint pathway as indicated by

44 ells arrested at the G2 checkpoint, in which UCN-01 abrogates cell cycle arrest, permitting cells to

45 Because UCN-01 abrogates checkpoint responses, this observation

46 It has been shown previously that UCN-01 abrogates DNA-damage-induced G(2) checkpoint most

47 re-sensitive Cdc2 mutations, to determine if UCN-01 abrogates G2 arrest through a Cdc2-dependent path

48 Our results suggest that UCN-01 abrogates G2 checkpoint function through inhibiti

49 nt human colon carcinoma HT29 cells and that UCN-01 abrogates the S-phase arrest or delay induced by

50 nal anticancer agent 7-hydroxystaurosporine (UCN-01) abrogates the G2 checkpoint in tumor cells and s

51 Having established that UCN-01 acted through Cdc2, we next assessed UCN-01's eff

52 taxia telangiectasia-mutated, are targets of UCN-01 action in vivo.

53 ciferase reporter plasmids and observed that UCN-01 activated the full-length p21(waf1/cip1) promoter

54 e pathways was required for p21 induction as UCN-01 activated this pathway, and genetic or chemical M

55 ent apoptotic activities of flavopiridol and UCN-01 against cultured B-CLL cells suggest that they ma

56 nduced cytotoxicity in p53-proficient cells, UCN-01 also blocked TMZ-induced Chk1 activation and tran

57 PD184352/UCN-01 also dramatically reduced clonogenic survival in

58 UCN-01 also had no effect on the association of p21 with

59 Because UCN-01 also inhibits protein kinase C (PKC), we screened

60 Consistent with such an upstream action, UCN-01 also promoted the hyperphosphorylation (activatio

61 mplex role, inhibition of Chk1 activity with UCN-01 also reduced mitotic exit.

62 Chk1/Chk2 inhibitor 7-hydroxystaurosporine (UCN-01) also increases camptothecin-induced gammaH2AX fo

63 UCN-01, an anticancer agent currently in Phase I clinica

64 UCN-01, an inhibitor of protein kinase C, Chk1, and cycl

65 elium, which was also markedly attenuated by UCN-01 and by CAS1609.

66 Inhibitors of Chk1, UCN-01 and caffeine, induced mitosis and abnormal nuclea

67 Interactions between UCN-01 and HMG-CoA reductase inhibitors (ie, statins) ha

68 ccordingly, abrogation of Chk1 activity with UCN-01 and its expression with shChk1 increased sensitiv

69 of U937 cells to subtoxic concentrations of UCN-01 and L744832 resulted in a dramatic increase in mi

70 e of Bim in synergistic interactions between UCN-01 and MEK1/2 inhibitors in human multiple myeloma c

71 In contrast, cotreatment of cells with UCN-01 and PD184352 did not substantially increase c-Jun

72 However, coexposure of U937 cells to UCN-01 and PD184352 induced a marked increase in p38 MAP

73 ombined exposure to the checkpoint abrogator UCN-01 and pharmacologic MEK1/2 inhibitors were examined

74 nteractions between the checkpoint abrogator UCN-01 and several pharmacological inhibitors of the mit

75 ions were observed in the structures between UCN-01 and the Chk1 kinase domain.

76 Interactions between the Chk1 inhibitor UCN-01 and the farnesyltransferase inhibitor L744832 wer

77 he protein kinase C (PKC) and Chk1 inhibitor UCN-01 and the heat shock protein 90 (Hsp90) antagonist

78 eported discrepancies in the pharmacology of UCN-01 and the influence of p53 status on treatment outc

79 6 cells to minimally toxic concentrations of UCN-01 and various statins (eg, lovastatin, simvastatin,

80 e inhibition of the XPA-ERCC1 interaction by UCN-01 and with the effect of UCN-01 on the phosphorylat

81 vating SAPK/JNK in leukemia cells exposed to UCN-01 and, in so doing, dramatically increase mitochond

82 interactions between 7-hydroxystaurosporine (UCN-01) and mitogen-activated protein kinase kinase 1/2

83 two PKC inhibitors, 7-hydroxystaurosporine (UCN-01) and N,N,N-trimethylsphingosine, and by two NO do

84 ant to wortmannin, sensitive to caffeine and UCN-01, and related to cyclin-dependent kinase phosphory

85 prolonged G2 arrest that can be targeted by UCN-01, and second, a tetraploid G1 arrest that can be t

86 ssibility that the PKC inhibitory actions of UCN-01 are responsible for synergistic interactions.

87 status in either the presence or absence of UCN-01, arguing against a causal relationship between th

88 The recommended phase II dose of UCN-01 as a 72-hour CIV is 42.5 mg/m(2)/d for 3 days.

89 1 was required for the cell cycle effects of UCN-01, as HCT116 lacking p21 (HCT116 p21(-/-)) was refr

90 Avid plasma protein binding of UCN-01, as measured during the trial, dictated a change

91 bition of Chk1 activity with Chk1 inhibitor (UCN-01, AZD7762, or CHIR-124) in normal cells increases

92 Lastly, cells incubated with UCN-01 before F-ara-A addition did not arrest in S-phase

93 Unfortunately, UCN-01 binds avidly to human plasma proteins, limiting b

94 Similar to flavopiridol, UCN-01 blocks cell cycle progression and promotes apopto

95 Whereas bryostatin 1 and UCN-01 both markedly enhanced ara-C-induced mitochondria

96 int of CNDAC-arrested cells was abrogated by UCN-01 but also in a minor population of cells that esca

97 od mononuclear cells after administration of UCN-01 but did not correlate with toxicity or activity.

98 uct failed to block apoptosis induced by Bay/UCN-01 but significantly attenuated MEK inhibitor (U0126

99 se C (PKC) inhibitor 7-hydroxystaurosporine (UCN-01) but not by the Cdc2 inhibitor, flavopiridol.

100 -2 mutant protein protected cells from ara-C/UCN-01- but not ara-C/bryostatin 1-mediated lethality.

101 nation of weekly infusions of FU and monthly UCN-01 can be administered safely and warrants further s

102 UCN-01 can be administered safely as an initial 72-hour

103 n together, these observations indicate that UCN-01 can modulate both Chk1 and Chk2 in intact cells a

104 We report that UCN-01 cannot induce mitosis in DNA-damaged FT210 cells

105 tion status of either XPA or ERCC1; however, UCN-01 caused dephosphorylation of an unidentified XPA-b

106 Here we report that UCN-01 caused loss of both serine 216 phosphorylation an

107 High concentrations of UCN-01 caused rapid activation of Cdc25C, which is attri

108 the p53 mutant cells, low concentrations of UCN-01 caused S phase cells to progress to G(2) before u

109 for the first time that p21 is required for UCN-01 cell cycle arrest.

110 on of growth with any measurable IC50 at low UCN-01 concentrations (i.e. 0 - 80 nM).

111 of growth with any measurable IC(50) at low UCN-01 concentrations (i.e. 0-80 nM).

112 that the Hsp90 antagonist 17-AAG potentiates UCN-01 cytotoxicity in a variety of human leukemia cell

113 ddition we show that inhibition of Chk1 with UCN-01 decreases dissociation of RPA from the chromatin

114 s leukemia (AML) blasts exposed to ara-C and UCN-01 demonstrated a selective loss in cloning potentia

115 The first phase I trial of UCN-01 demonstrated a very prolonged half-life.

116 The first clinical trial of UCN-01 demonstrated very prolonged half-life (approximat

117 lly lower than that required to inhibit PKC; UCN-01 did not demonstrate this selectivity for checkpoi

118 Coadministration of 17-AAG and UCN-01 did not modify expression of Hsp90, Hsp27, phosph

119 rogation and subsequent apoptosis induced by UCN-01 do not necessarily correlate with reproductive ce

120 checkpoint abrogator 7-hydroxystaurosporine (UCN-01) dramatically induces apoptosis in a variety of h

121 cells to a marginally toxic concentration of UCN-01 (e.g., 150 nM) for 18 h resulted in phosphorylati

122 In addition, UCN-01 efficiently abrogated both the initiation and mai

123 ic concentrations of 17-AAG (eg, 400 nM) and UCN-01 (eg, 75 nM) triggered a pronounced increase in mi

124 These results suggest a mechanism by which UCN-01 enhances the cytotoxicity of agents that cause an

125 This novel mechanism, by which UCN-01 exerts its antiproliferative effect, represents a

126 receded Cdc2 dephosphorylation (Tyr15) after UCN-01 exposure.

127 Subsequent incubation with UCN-01 failed to abrogate arrest.

128 The minimal promoter region required for UCN-01 (from -110 bp to the transcription start site) wa

129 UCN-01 had no effect on PKCzeta and inhibited kinase act

130 In vitro phosphorylation revealed that UCN-01 had no effect on the phosphorylation/dephosphoryl

131 UCN-01 has interesting preclinical features: it inhibits

132 Hence, UCN-01 has multiple effects depending on concentration a

133 11-7082, SN-50) and the checkpoint abrogator UCN-01 have been examined in human multiple myeloma (MM)

134 of normal and tumor cells with high doses of UCN-01 (i.e. 300 nM) revealed a necessary role for a fun

135 was 100-fold more resistant to inhibition by UCN-01 (IC50, 1040 nM).

136 monstrated with the protein kinase inhibitor UCN-01 in a phosphoserine-dependent manner.

137 Thus, use of UCN-01 in combination with ara-C decreases Chk1 phosphor

138 clinical trial of ara-C in combination with UCN-01 in patients with relapsed AML.

139 However, inhibition of Chk1 by UCN-01 in S-phase-arrested cells resulted in an abrogati

140 nvestigated the growth inhibitory effects of UCN-01 in several normal and tumor-derived human breast

141 In 36 primary T-ALL cells, the IC50s of UCN-01 in the 27 p16 (-) cells (43+/-52 nM) was signific

142 This resistance to UCN-01 in the p53 wild-type cells correlated with suppre

143 ntrast, Cds1 was refractory to inhibition by UCN-01 in vitro, and Cds1 was still phosphorylated in ir

144 ombining IUdR and caffeine-like drugs (e.g., UCN-01) in p53-deficient human tumors may lead to a grea

145 Failure to abrogate G2 arrest was not due to UCN-01-inactivation at the elevated temperature because

146 Although not in itself toxic, UCN-01 increased the cytotoxicity of TMZ 5-fold, primari

147 kinase C (PKC) inhibitors staurosporine and UCN-01, indicating a role for PKC in monocyte activation

148 The findings suggest that flavopiridol and UCN-01 induce apoptosis of B-CLL cells through different

149 Flavopiridol and UCN-01 induced concentration-dependent apoptosis of most

150 e in the p21 mRNA half-life, suggesting that UCN-01 induced p21 at the transcriptional level.

151 in SN38-mediated induction of p21(WAF1), and UCN-01 induced S, but not G(2) progression.

152 it was unable to protect them from PD184352/UCN-01-induced apoptosis despite enhancing Akt activatio

153 diated adherence conferred resistance to Bay/UCN-01-induced apoptosis.

154 s, there was no p21(Waf1/Cip1) induction nor UCN-01-induced apoptosis.

155 d to prevent MEK1/2 inhibitors from blocking UCN-01-induced Bim(EL) phosphorylation/degradation or ce

156 erence, remained fully sensitive to PD184352/UCN-01-induced cell death.

157 They also suggest a role for Chk1 in UCN-01-induced ERK1/2 activation, implying the existence

158 Although Bay modestly blocked UCN-01-induced extracellular signal-regulated kinase (ER

159 which have wild-type Cdc2, were sensitive to UCN-01-induced G2 checkpoint abrogation.

160 gnificantly attenuated MEK inhibitor (U0126)/UCN-01-induced lethality.

161 related apoptotic pathways to MEK inhibitors/UCN-01-induced leukemic cell death.

162 e MEK inhibitor PD184352 (10 microM) blocked UCN-01-induced MAPK activation and was accompanied by ma

163 PD184352/UCN-01-induced mitochondrial dysfunction and apoptosis w

164 sed MEK inhibitors (e.g., PD184352 or U0126)/UCN-01-induced mitochondrial dysfunction, activation of

165 se C (PKC) inhibitor 7-hydroxystaurosporine (UCN-01) induces apoptosis independently of p53 and prote

166 purified Wee1Hu was relatively resistant to UCN-01-inhibition.

167 f normal and AT fibroblasts with caffeine or UCN-01, inhibitors of ATR (AT mutated and Rad3 related)

168 e-inducible checkpoint, we hypothesized that UCN-01 inhibits a component of the signal transduction p

169 UCN-01 inhibits Chk1/2, which should activate the mitosi

170 rted by in vitro kinase assays, showing that UCN-01 inhibits Chk2 immunoprecipitated from HCT116 cell

171 eloid leukemia cells by bryostatin 1 but not UCN-01 involves activation of the extrinsic, receptor-me

172 se II dose of FU in combination with monthly UCN-01 is 2,600 mg/m(2).

173 The small molecule UCN-01 is a cyclin-dependent kinase (CDK) modulator show

174 UCN-01 is a potent inhibitor of the S- and G2-M-phase ce

175 ery 4 weeks (in second and subsequent cycles UCN-01 is administered as a 36-h infusion).

176 Based on this novel feature, UCN-01 is administered as a 72-h continuous infusion eve

177 n of the DNA damage-induced G2 checkpoint by UCN-01 is mediated through the inhibition of the Cdc25C

178 ndicating that G(2) checkpoint abrogation by UCN-01 is p53 independent.

179 7-Hydroxystaurosporine (UCN-01) is a selective protein kinase C inhibitor in cli

180 ond cdk modulator tested in clinical trials, UCN-01, is a PKC inhibitor that can also modulate cdk ac

181 A significantly reduced the lethality of the UCN-01/L744832 regimen.

182 tutively active MEK significantly attenuated UCN-01/L744832-induced apoptosis.

183 and MEK resulted in further protection from UCN-01/L744832-mediated lethality.

184 but not dominant-negative caspase-8 blocked UCN-01/L744832-mediated mitochondrial dysfunction and ap

185 indicate that exposure of leukemic cells to UCN-01 leads to activation of the MAPK cascade and that

186 Potentiation of UCN-01 lethality by lovastatin was associated with disru

187 gative caspase-9 dramatically diminished Bay/UCN-01 lethality without altering JNK or cdc2/cdk1 activ

188 orylation, significantly sensitized cells to UCN-01 lethality.

189 UCN-01 markedly potentiated the cytotoxicity of CPT also

190 Moreover, UCN-01 may abrogate checkpoints induced by genotoxic str

191 Our results suggest that agents like UCN-01 may be useful as a p16-selective therapy for T-AL

192 Although UCN-01 may inhibit several serine-threonine kinases, the

193 ity remained unchanged, which suggested that UCN-01 may interrupt IR-induced p53 response by inhibiti

194 f CPT-induced S- and G2-phase checkpoints by UCN-01 may provide an effective strategy for enhancing t

195 apacity of PD98059 but not PD184352 to block UCN-01-mediated Bim(EL) phosphorylation and to potentiat

196 ether, these findings indicate that although UCN-01-mediated Chk1 inhibition and Cdc2 activation are

197 ally, coadministration of R115777 diminished UCN-01-mediated ERK1/2 activation and markedly potentiat

198 Collectively, these findings argue that UCN-01-mediated ERK1/2 activation leads to Bim(EL) phosp

199 at pRb and not p53 function is essential for UCN-01-mediated G1 arrest.

200 Bay/UCN-01-mediated lethality involved mitochondrial dysfunc

201 espectively, significantly attenuated 17-AAG/UCN-01-mediated lethality.

202 icantly reduced susceptibility to lovastatin/UCN-01-mediated lethality.

203 0125 or D-JNKI1 peptide markedly reduced Bay/UCN-01-mediated mitochondrial dysfunction and apoptosis

204 Coadministration of L744832 blocked UCN-01-mediated phosphorylation of mitogen-activated pro

205 f cells with S65A Bim, a mutant resistant to UCN-01-mediated phosphorylation, significantly sensitize

206 of Cdc2 sensitized cells to the lethality of UCN-01/MEK inhibitor regimen, whereas Cdc2 knockdown by

207 y CD138(+) MM cells were also susceptible to UCN-01/MEK inhibitor-mediated apoptosis.

208 of Bim(EL) by shRNA substantially diminished UCN-01/MEK inhibitor-mediated Bax/Bak activation and apo

209 MEK1 significantly protected cells from the UCN-01/MEK1/2 inhibitor regimen without modifying Cdc2 a

210 on of either Bcl-2 or Bcl-x(L) did not alter UCN-01/MEK1/2 inhibitor-mediated modifications in Bim(EL

211 Preliminary evidence suggests UCN-01 modulation of both PKC substrate phosphorylation

212 ur results show the different sensitivity to UCN-01 of normal compared to tumor cells is dependent on

213 (NER) pathway, we determined the effects of UCN-01 on NER by measuring its effects on the interactio

214 The effect of UCN-01 on the cell cycle is thus quite different from st

215 interaction by UCN-01 and with the effect of UCN-01 on the phosphorylation/dephosphorylation of an XP

216 o M of the cyclin-dependent kinase inhibitor UCN-01 or 1 micro M of the P-glycoprotein inhibitor tari

217 e to irinotecan and a Chk1 inhibitor (either UCN-01 or AZD7762), either as single agents or in combin

218 platelets, and this was inhibited by either UCN-01 or CAS1609.

219 toxic concentrations of the Chk1 inhibitors UCN-01 or Chk1i modestly induced DNA damage, accompanied

220 actions between Src and Chk1 inhibitors (eg, UCN-01 or Chk1i) were examined in vitro and in vivo.

221 Trials of shorter infusions of UCN-01 or in combination with standard chemotherapeutic

222 pon treatment with protein kinase inhibitors UCN-01 or SB203580.

223 Addition of caffeine, UCN-01, or inhibitors of checkpoint pathways or silencin

224 The Chk1 inhibitor, 7-hydroxystaurosporine (UCN-01), overcomes both S and G(2) arrest preferentially

225 An inhibitor of Chk1 kinase activity, UCN-01, overcomes the HuCdc6 mediated G(2) arrest indica

226 By inhibiting a p53-independent pathway, UCN-01 overrode DOX-induced G2 arrest and instead induce

227 Lastly, although UCN-01 +/- PD184352 did not induce p21(CIP1), stable exp

228 down by siRNA enhanced lethality mediated by UCN-01/PD184352.

229 FU and UCN-01 pharmacokinetics were obtained on all patients, a

230 UCN-01 potentiated the cytotoxicity of CPT and reduced b

231 n shown in some, but not all, instances that UCN-01 potentiates the cytotoxicity of DNA-damaging agen

232 n kinase C inhibitor 7-hydroxystaurosporine (UCN-01) potentiates the cytotoxic effects of fluorouraci

233 In addition, UCN-01 potently inhibited the ability of Chk1 to phospho

234 Here we show that UCN-01 prevented IR-induced p53 up-regulation and p53 ph

235 UCN-01 prevented the increase of cyclin A/cyclin-depende

236 progression induced by low concentrations of UCN-01, probably because Cdc25C is also inhibited by the

237 Moreover, UCN-01 promoted the accumulation of p21 at the mRNA leve

238 We have reported previously that UCN-01 promotes G(1)-S cell cycle arrest in a battery of

239 mpared with untreated cells, suggesting that UCN-01 reduced the XPA-ERCC1 interaction.

240 ese findings suggest that the MEK inhibitors/UCN-01 regimen primarily induces leukemic cell apoptosis

241 The Chk1 specific inhibitor UCN-01 repressed all of these effects.

242 Sequential treatment with SN-38 followed by UCN-01 resulted in enhancement of cytotoxicity by apopto

243 Exposure of U266 or RPMI8226 cells to UCN-01 resulted in ERK1/2 activation-associated Bim(EL)

244 Coexposure to statins and UCN-01 resulted in inactivation of ERK1/2 and Akt, accom

245 Coadministration of PD184352 and UCN-01 resulted in reduced binding of the cdc25C phospha

246 versely, concurrent treatment with SN-38 and UCN-01 resulted in S-phase checkpoint override, an ampli

247 lls to Bay 11-7082 (Bay) in combination with UCN-01 resulted in the abrogation of NF-kappaB/DNA bindi

248 Cotreatment of U937 cells with PD184352 and UCN-01 resulted in the activation of procaspase-3, -9, a

249 of cells to ara-C and bryostatin 1 (but not UCN-01) resulted in sustained release of tumor necrosis

250 treated with bryostatin 1, staurosporine, or UCN-01 revealed the appearance of a slowly migrating spe

251 ic regulators are downstream consequences of UCN-01's actions.

252 UCN-01 acted through Cdc2, we next assessed UCN-01's effect on the Cdc2-inhibitory kinase, Wee1Hu, a

253 In contrast, UCN-01-stimulated decreases in antiapoptosis proteins we

254 Finally, coadministration of BMS354825 and UCN-01 suppressed human MM tumor growth in a murine xeno

255 his effect was observed at concentrations of UCN-01 that alone were not cytotoxic and had no detectab

256 acy of drugs such as 7-hydroxystaurosporine (UCN-01) that abrogate S and G(2) arrest.

257 agents caffeine and 7-hydroxystaurosporine (UCN-01) that inhibit the checkpoint kinases ATM/ATM and

258 int activation since 7-hydroxystaurosporine (UCN-01), the specific Chk1 inhibitor CHIR-124, or transf

259 ffeine, the nonspecific inhibitor of ATR, or UCN-01, the nonspecific inhibitor of CHK1, but also the

260 C1 proteins was elevated in cells exposed to UCN-01, the treatment resulted in a decreased ERCC1 leve

261 /2 activation and antagonized the ability of UCN-01 to activate ERK1/2.

262 horylated Akt kinase declined on addition of UCN-01 to the ara-C infusion, an action accompanied by a

263 tely 600 h), due to high binding affinity of UCN-01 to the human alpha-1-acid glycoprotein.

264 hk1 kinase inhibitor 7-hydroxystaurosporine (UCN-01) to F-ara-A-arrested S-phase cells resulted in a

265 rogator of p53-independent checkpoint (e.g., UCN-01) to the DOX-PTX sequence.

266 Selectivity of UCN-01 toward Chk1 over cyclin-dependent kinases can be

267 To study UCN-01 transcriptional activation of p21, we used severa

268 The UCN-01 treated normal cells arrested in G1 phase and dis

269 ing of ERCC1 to XPA in nuclear extracts from UCN-01-treated cells compared with untreated cells, sugg

270 n of Bim(EL) with both Bcl-2 and Bcl-x(L) in UCN-01-treated cells, leading to Bax/Bak conformational

271 found that Wee1Hu was indeed inactivated in UCN-01-treated cells, possibly just prior to Cdc2 activa

272 prevention of Ras and ERK1/2 activation, in UCN-01-treated cells, resulting in the synergistic induc

273 activity was found in the cell extracts from UCN-01-treated cells.

274 d after immunoprecipitation of cytosols from UCN-01-treated HL60 cells.

275 derwent apoptosis 3 h after the beginning of UCN-01 treatment.

276 The mean maximal plasma concentration of UCN-01 was 33.5 micromol/L.

277 UCN-01 was administered once every 4 weeks, immediately

278 to As(2)0(3), apoptosis induced by PD184352/UCN-01 was not blocked by the free-radical scavenger N-a

279 ara-C lethality by bryostatin 1 (but not by UCN-01) was reversed by coadministration of TNF soluble

280 d the structural basis of Chk1 inhibition by UCN-01, we determined the crystal structure of the Chk1

281 n 1 and the PKC inhibitors staurosporine and UCN-01 were examined with respect to modulation of 1-[be

282 C and Chk1 inhibitor 7-hydroxystaurosporine (UCN-01) were compared with respect to potentiation of 1-

283 rs flavopiridol and 7 hydroxy-staurosporine (UCN-01) were examined for their effects on B-cell chroni

284 The ability of UCN-01, when combined with PD184352, to antagonize cdc25

285 ppressed the combined effects of LY294002 or UCN-01, whereas dominant-negative Akt expression was suf

286 checkpoint abrogator 7-hydroxystaurosporine (UCN-01), which markedly potentiates camptothecin cytotox

287 by nucleoside analogues sensitizes cells to UCN-01, which appears to activate signaling for death me

288 from staurosporine, a structural analogue of UCN-01, which arrests normal cells in both G1 and G2, wh

289 ed with otherwise nontoxic concentrations of UCN-01, which caused rapid onset of apoptosis without ce

290 ch down-regulates PKC, and staurosporine and UCN-01, which directly inhibit the enzyme, circumvent re

291 ata demonstrate the NER-inhibitory action of UCN-01, which is associated with the inhibition of the X

292 ry epithelial cells w were very sensitive to UCN-01 with an IC(50) of 10nM tumor cells displayed litt

293 mary epithelial cells were very sensitive to UCN-01 with an IC50 of 10 nM, tumor cells displayed litt

294 e findings suggest that a strategy combining UCN-01 with disruption of the IkappaB kinase (IKK)/Ikapp

295 kinase 1 (cTAK1) were potently inhibited by UCN-01 with IC50s of 11 and 27 nM, respectively.

296 tiple signaling pathways, e.g., by combining UCN-01 with MEK inhibitors, may represent a novel antile