ライフサイエンスコーパス: cyclopamine

1 iofacial defects by a known human teratogen, cyclopamine.

2 presence of the Smoothened (SMO) inhibitor, cyclopamine.

3 ent + ethionine (MCDE) diets with or without cyclopamine.

4 aining neural tube with DiI/CSRE and applied cyclopamine.

5 ty and better aqueous solubility compared to cyclopamine.

6 l class of hedgehog antagonists derived from cyclopamine.

7 reated with the Hedgehog signaling inhibitor cyclopamine.

8 e Shh signal transduction pathway inhibitor, cyclopamine.

9 ed oligodendrocytes, even in the presence of cyclopamine.

10 f Shh signaling: anti-Shh (5E1) antibody and cyclopamine.

11 o produce verazine, a predicted precursor to cyclopamine.

12 activity but are structurally distinct from cyclopamine.

13 g antagonism of the Shh signaling pathway by cyclopamine.

14 oo, the appearance of OLPs was suppressed by cyclopamine.

15 -/-) basal forebrain and this was blocked by cyclopamine.

16 cyclic DE ring junction found in jervine and cyclopamine.

17 and small molecule inhibitors vismodegib and cyclopamine.

18 COT-1 cells were treated with SMO antagonist cyclopamine.

19 ; the transducer of Hh signaling) inhibitor, cyclopamine.

20 cell death in contrast to the Smo inhibitor cyclopamine.

21 anism similar to that of the known teratogen cyclopamine.

22 rtion of the Veratrum alkaloids jervine (1), cyclopamine (2), and veratramine (3) is reported.

23 in some ways shares similarities to that of cyclopamine, a commonly used pathway inhibitor.

24 Exposure of the gpc1 morphants to cyclopamine, a Hedgehog antagonist, partially rescued th

25 Cyclopamine, a hedgehog pathway inhibitor, significantly

26 h pathway activity, which is suppressible by cyclopamine, a Hh pathway antagonist.

27 The administration of cyclopamine, a Hh signaling inhibitor, decreases both in

28 discovery of Shh pathway inhibitors such as cyclopamine, a naturally occurring alkaloid and ornithin

29 Cyclopamine, a plant Veratrum alkaloid, is a natural pro

30 ain unclear, the direct inhibition of Smo by cyclopamine, a plant-derived steroidal alkaloid, suggest

31 We find that cyclopamine, a potent antagonist of Shh signaling, can d

32 Cyclopamine, a potent inhibitor of hedgehog signalling,

33 consistently express the GLI genes and that cyclopamine, a SHH signaling inhibitor, inhibits the pro

34 Exposure to cyclopamine, a steroid alkaloid that blocks Sonic hedgeh

35 , we investigate the biosynthetic pathway to cyclopamine, a steroid alkaloid that shows promising ant

36 nds act similarly to the Hedgehog antagonist cyclopamine, a teratogenic plant alkaloid, which had bee

37 Using this system, we demonstrate that cyclopamine, a widely used Hh antagonist, induces a cili

38 when cotreated with the Smoothened inhibitor cyclopamine, A549 cells became more sensitive to schwein

39 Blockade of Shh signaling with cyclopamine abolished the Shh-mediated induction of Gli1

40 ng pathway with a pharmacological inhibitor, cyclopamine, abolished the CEPO-induced neurogenesis.

41 a V. californicum RNA-seq dataset using the cyclopamine accumulation profile as a predefined model f

42 ne derivatives or other compounds that mimic cyclopamine action in binding to and antagonizing Smooth

43 ahelical bundle in a manner that antagonizes cyclopamine action.

44 hat the Smoothened receptor (Smo) antagonist cyclopamine acts as a potent and selective inhibitor of

45 Finally, in a rodent CCA in vivo model, cyclopamine administration increased apoptosis in CCA ce

46 Cyclopamine also can reverse the retention of partially

47 armacologic inhibition of Shh signaling with cyclopamine also hindered fibroblast activation and exac

48 Cyclopamine also suppresses cell growth in vitro and cau

49 Together, our data demonstrate that cyclopamine alters APP processing and Abeta generation b

50 more newborn astrocytes were found in the HI+cyclopamine (an antagonist of the hedgehog protein)+UCBM

51 s, SAG (an Hh agonist) up-regulated, whereas cyclopamine (an Hh antagonist) repressed OPN expression

52 escued the inhibition of cell growth by KAAD-cyclopamine, an antagonist of hedgehog signaling element

53 on in the orJ retina is further inhibited by cyclopamine, an antagonist of Hh signaling.

54 In Huh7.5 cells, we found that cyclopamine, an Hh pathway antagonist, reduced HCV RNA l

55 to normal primary liver SEC with or without cyclopamine, an Hh signaling inhibitor.

56 We find that cyclopamine, an inhibitor of Hh signaling, causes strong

57 for BBS-mediated SCLC proliferation, because cyclopamine, an inhibitor of the Shh pathway, hampered t

58 LgDel embryos treated with cyclopamine, an Shh inhibitor, or carrying mutations in

59 IPI-926 (compound 28), a novel semisynthetic cyclopamine analogue with substantially improved pharmac

60 onjugated ketone led to the discovery of new cyclopamine analogues with improved pharmaceutical prope

61 igated the effects of Hedgehog inhibition by cyclopamine and 5E1 in cultured human CCC cell lines and

62 In addition, cyclopamine and 5E1 inhibited the growth of CCC xenograf

63 Cyclopamine and 5E1 treatments effectively inhibited cel

64 c areas and a decrease in mitotic figures in cyclopamine and 5E1-treated CCC xenograft tumors.

65 avorable pharmacokinetic profile relative to cyclopamine and compound 2.

66 GDC-0449 in the micromolar range, but not by cyclopamine and CUR61414.

67 ffects of two hedgehog signaling inhibitors, cyclopamine and forskolin, on gonad explant cultures.

68 aling in the regenerating fin by exposure to cyclopamine and found a dose-dependent inhibition of fin

69 IP combination drug delivery of paclitaxel, cyclopamine and gossypol, resulting in tumor growth inhi

70 lly safer and less expensive alternatives to cyclopamine and its pharmaceutical analogues for cancer

71 t develop on pharyngeal or ventral tongue in cyclopamine and jervine cultures, or in the tongue midli

72 The steroidal alkaloids, cyclopamine and jervine, that specifically disrupt the S

73 The activation is suppressed by cyclopamine and other inhibitors of Hedgehog signaling a

74 Our data provide strong evidence that cyclopamine and perhaps other SMO antagonists are potent

75 Cyclopamine and sonic hedgehog (shh) mRNA overexpression

76 eviously identified include the plant sterol cyclopamine (and its therapeutically useful synthetic mi

77 l effects by the hedgehog pathway inhibitor, cyclopamine, and 4) unresponsiveness of Smoothened-/- mo

78 gically inhibiting the Hedgehog pathway with cyclopamine, and maximal rescue occurred when embryos we

79 d by shh overexpression cannot be rescued by cyclopamine, and no further embryonic muscle growth occu

80 dorsalized by the sonic hedgehog antagonist cyclopamine, and that express, as a total population, ca

81 and tongue cultures with standard medium or cyclopamine, and was conspicuously localized in the base

82 g in vitro and in vivo models, we identified cyclopamine as a novel regulator of gamma-secretase-medi

83 Cyclopamine at concentrations of 20-100 nM blocks the re

84 d chick embryos with the hedgehog antagonist cyclopamine at various stages of limb development.

85 rescue occurred when embryos were exposed to cyclopamine between 5.5 and 13 hours post-fertilization.

86 competed with BODIPY (boron-dipyrromethene)-cyclopamine binding at different FZDs and inhibited WNT-

87 GSA-10 does not recognize the classic bodipy-cyclopamine binding site.

88 and pharmacological dissection of two BODIPY-cyclopamine binding sites.

89 y in various cell-based assays and of BODIPY-cyclopamine binding to human Smo.

90 protein yield structural insights regarding cyclopamine binding to the Smoothened receptor.

91 The Hedgehog antagonist cyclopamine blocked expression of the Hh pathway targets

92 Inhibition of the SHH pathway with cyclopamine blocks the Gli response and significantly re

93 s did not compete with fluorescently labeled cyclopamine, BODIPY-cyclopamine, for direct binding to S

94 presence of the smoothened (SMO) antagonist, cyclopamine, both in vitro in the mouse basal cell carci

95 sterol transport, we show that the action of cyclopamine cannot be explained by inhibition of intrace

96 Combination of gemcitabine and cyclopamine completely abrogated metastases while also s

97 ntaining two drug conjugates: HPMA copolymer-cyclopamine conjugate (P-CYP) preferentially toxic to ca

98 Apoptotic induction caused by cyclopamine could be rescued in part by enforced express

99 Intrathecal or peripheral administration of cyclopamine (CP), a specific inhibitor of Sonic Hedgehog

100 Cyclopamine (CPA), a potent inhibitor of the Hedgehog pa

101 We applied the hedgehog signaling inhibitor, cyclopamine (Cyc), to chick embryos after CNCC ablation

102 articles (MSNs) containing an SHh inhibitor, cyclopamine (CyP), and the combination of chemotherapeut

103 We demonstrate that cyclopamine decreases Abeta generation by altering APP r

104 nes) by both Sonic hedgehog and PDGF-BB in a cyclopamine-dependent manner in CCA cells.

105 ess Mad3 in response to Shh stimulation in a cyclopamine-dependent manner.

106 These efforts have focused largely on cyclopamine derivatives or other compounds that mimic cy

107 Treatment with cyclopamine did not affect inhibition of germ cell meios

108 In wild-type mice, cyclopamine did not affect renal Shh expression but did

109 Pretreatment of these cells with cyclopamine did not shift the cisplatin IC50.

110 rthermore, the treatment of INS-1 cells with cyclopamine diminishes endogenous insulin mRNA expressio

111 on of Hh pathway signaling by treatment with cyclopamine does not block prostate formation in explant

112 terol synthesis inhibitor AY-9944 shows that cyclopamine does not induce malformations by interfering

113 ort here that chronic oral administration of cyclopamine dramatically reduces ( approximately 66%) UV

114 This extracortial sink is a cyclopamine drug-conjugated, collagen-based hydrogel.

115 Exposing avian embryos to cyclopamine during critical periods of craniofacial deve

116 Blocking maternal hedgehog signaling by cyclopamine eliminates primary motoneurons, but not medi

117 septation should occur, embryos treated with cyclopamine exhibited pulmonary atresia, pulmonary steno

118 The results suggests that cyclopamine expands the endodermal region where Shh sign

119 th fluorescently labeled cyclopamine, BODIPY-cyclopamine, for direct binding to Smoothened.

120 ion of the SHH pathway was down-regulated by cyclopamine, further confirming that cyclopamine inhibit

121 f embryogenesis with the steroidal alkaloid, cyclopamine, further reveals that the requirement for a

122 Unlike cyclopamine, GANT61 induced transient cellular accumulat

123 ersely, inhibition of Hh signaling with KAAD-cyclopamine, Gli antagonists or antibody to Shh reduced

124 confirm the role of Gli1, hedgehog inhibitor cyclopamine, Gli1 siRNA and Gli1(-/-) mouse embryonic fi

125 The steroidal alkaloid cyclopamine has both teratogenic and antitumor activitie

126 Tongues cultured with cyclopamine have a dose-dependent expansion of Shh and B

127 re loaded with paclitaxel (cytotoxic agent), cyclopamine (hedgehog inhibitor), and gossypol (Bcl-2 in

128 ouble mutants and could be phenocopied using cyclopamine in culture.

129 peutic efficacy of the Hh pathway antagonist cyclopamine in preclinical models of medulloblastoma, th

130 is sufficient to confer virus resistance to cyclopamine in vitro and that cyclopamine is able to red

131 the production of steroidal alkaloids (e.g., cyclopamine) in corn lily.

132 oligonucleotides or the teratogenic alkaloid cyclopamine, in order to dissect the separate roles of H

133 otably, inhibition of hedgehog signalling by cyclopamine induced apoptosis and blocked proliferation

134 Cyclopamine induced malformation of both foregut and ant

135 In comparison, the classical Smo inhibitor, cyclopamine, induced modest cytotoxicity.

136 Shh treatment blocked cyclopamine-induced anoikis.

137 Cyclopamine-induced malformations in chick embryos are a

138 These findings suggest that cyclopamine-induced teratogenesis is due to a more direc

139 Regenerated spinal cords expressed Shh, and cyclopamine inhibited CT induction.

140 Cyclopamine inhibited Hh-pathway activation and inductio

141 Cyclopamine inhibited OLP development in cultures of mou

142 Smo agonist stimulated and a Smo antagonist (cyclopamine) inhibited both phosphorylation of Smo by GR

143 ary localization, whereas the Smo antagonist cyclopamine inhibits ciliary localization.

144 Cyclopamine inhibits hRSV through a novel, Smo-independe

145 ated by cyclopamine, further confirming that cyclopamine inhibits the SHH signaling pathway; SHH down

146 Cyclopamine instead acts independently of Smo to decreas

147 infusing the neuroblast migration inhibitor cyclopamine into HVC of male Gambel's white-crowned spar

148 Attenuation of CIPN by cyclopamine (intradermal and intraganglion), which inhib

149 en-membered D-ring semisynthetic analogue of cyclopamine, IPI-269609 (2), was shown to have greater a

150 Cyclopamine is a teratogenic steroidal alkaloid that cau

151 resistance to cyclopamine in vitro and that cyclopamine is able to reduce virus titers in a mouse mo

152 nanoluciferase (Nluc) and binding of BODIPY-cyclopamine is assessed by quantifying resonance energy

153 ive total synthesis of the Veratrum alkaloid cyclopamine is disclosed.

154 Supply of cyclopamine is limited, as the current source is solely

155 at the potent antagonism of Shh signaling by cyclopamine is not a general property of steroidal alkal

156 We have tested whether this activity of cyclopamine is related to disruption of cellular cholest

157 In cultures with cyclopamine, jervine, or blocking antibody, fungiform pa

158 aling pathway was disrupted with addition of cyclopamine, jervine, or the 5E1 blocking antibody.

159 emorgin C or inhibition of Hh signaling with cyclopamine-KAAD abrogated the stroma-induced chemotoler

160 w that inhibition of SHH/GLI1 signaling with cyclopamine-KAAD, as well as silencing GLI1 gene express

161 commercially available SMO ligands (SANT-1, cyclopamine-KAAD, SAG1.3 and purmorphamine), and pharmac

162 ignaling by smoothened (SMO) antagonist KAAD-cyclopamine (keto-N-aminoethylaminocaproyldihydrocinnamo

163 Our results also indicate that cyclopamine may act by influencing the balance between a

164 hat treatment with the Hh pathway antagonist cyclopamine may lead to rapid resolution of the disease.

165 Antagonists of this pathway such as cyclopamine may therefore be useful for treatment of bas

166 as/Fas ligand interactions are necessary for cyclopamine-mediated apoptosis in these cells, a process

167 Cyclopamine-mediated inhibition of the Shh signaling med

168 Cyclopamine-mediated reduction in anoikis resistance was

169 s modulatory effect is distinct from that of cyclopamine mimics, from Hh-mediated regulation, and fro

170 tly resistant or have acquired resistance to cyclopamine mimics.

171 dramatically shift the IC50 concentration of cyclopamine needed to inhibit Gli activity in these cell

172 ther affected by blocking Shh signaling with cyclopamine nor by genetic removal of several BMP activi

173 LI2 could rescue the antagonistic effects of cyclopamine on OPN expression.

174 Second, by comparing the effects of cyclopamine on Shh signaling with those of compounds kno

175 ion of two separate binding sites for BODIPY-cyclopamine on the SMO transmembrane core in live cells

176 Inhibition of Shh signaling, by addition of cyclopamine or a function-blocking antibody, resulted in

177 Blocking the pathway with cyclopamine or anti-SHH antibodies inhibits the prolifer

178 Conversely, when Hh signaling was blocked by cyclopamine or by removing Smoothened (Smo), a positive

179 We show that cyclopamine or synthetic derivatives with improved poten

180 e metastatic prostate cancer cell lines with cyclopamine or through GLI1 RNA interference leads to in

181 g of the Wnt and Hh pathways using CAY10404, cyclopamine, or itraconazole significantly reduced the m

182 Local delivery of the Shh inhibitor, cyclopamine, or Shh silencing both recapitulated this ef

183 poietic progenitors and leukemic stem cells; cyclopamine preferentially reduced "ALDH-high" cells by

184 y activity, and blocking the Hh pathway with cyclopamine prevented colobomas in ptch2(uta1) mutant em

185 ss, the chemical inhibitor of Shh signaling, cyclopamine, produced a graded inhibition of Gli gene ex

186 The steroidal alkaloid cyclopamine produces cyclopia and holoprosencephaly when

187 In an orthotopic xenograft model, cyclopamine profoundly inhibited metastatic spread; only

188 signaling with increasing concentrations of cyclopamine progressively reduces insulin promoter activ

189 not due to inhibition of Smoothened (Smo) by cyclopamine; rather, we find that neither maternal nor z

190 Instead, cyclopamine redirects APP-CTFs to the lysosome.

191 on of versican and collagen type IX, whereas cyclopamine reduced expression of these chondroitin sulf

192 e pharmacological inhibitor of Shh signaling cyclopamine reduced hippocampal neural progenitor prolif

193 In addition, cyclopamine reduced matrix expression and mitigated fibr

194 Inhibition of Hh signaling by cyclopamine reduced PLK2, but not PLK1 or PLK3, messenge

195 ls, treatment with the Smoothened inhibitor, cyclopamine, reduced miR-25 expression, suggesting Hedge

196 reatic cancer cell lines, Hh inhibition with cyclopamine resulted in down-regulation of snail and up-

197 hway using the pharmacological Hh inhibitor, cyclopamine, results in an overall decrease in osteoclas

198 Blocking signaling with cyclopamine reveals that the crucial stage, for both cre

199 Cyclopamine reveals the capacity of a broad region of th

200 Cyclopamine reversed these effects.

201 These observations reveal the mechanism of cyclopamine's teratogenic and antitumor activities and f

202 We found that cyclopamine significantly arrested the growth of KCOT-1

203 d NOTCH signaling pathway and confirmed that cyclopamine significantly arrested the growth of KCOT-1

204 dary heart field with the hedgehog inhibitor cyclopamine significantly reduced proliferation.

205 urthermore, inhibition of Shh signaling with cyclopamine stimulated Six1(-/-) lungs to grow and branc

206 on of solanidine, an alkaloid that resembles cyclopamine structurally but that does not disrupt Shh s

207 vitro and in rat UGS explants cultured with cyclopamine, suggesting that SHH-signalling is not criti

208 Hh pathway blockade with cyclopamine suppressed GLI1 activation and enhanced tumo

209 Here, we show that cyclopamine tartrate (CycT) strongly suppresses the grow

210 -aminoethylaminoethylcaproyldihydrocinnamoyl cyclopamine, the Gli2 ASO was still able to inhibit prol

211 l as cultured vibrissa explants treated with cyclopamine to block Shh signaling.

212 sonic hedgehog signaling through addition of cyclopamine to cultures.

213 the presence or absence of the Hh inhibitor cyclopamine to determine whether Hh-pathway activation d

214 Using cyclopamine to inhibit hedgehog signaling, we show that

215 tory effect is mediated by direct binding of cyclopamine to the heptahelical bundle of Smoothened (Sm

216 Comparison of the effects of cyclopamine to those of the holoprosencephaly-inducing c

217 Treatments with cyclopamine, to block Hh signaling at different stages,

218 nfusion of Shh and a Shh receptor inhibitor, cyclopamine, to ischemic animals further elevated and su

219 nd cortical trajectories resembling those of cyclopamine-treated cIN.

220 ed from the neural tube in the CNCC-ablated, cyclopamine-treated embryos but not in untreated CNCC-ab

221 Somites in cyclopamine-treated embryos show Pax7 expression through

222 holesterol does not restore Shh signaling in cyclopamine-treated explants.

223 hibited metastatic spread; only one of seven cyclopamine-treated mice developed pulmonary micrometast

224 Our in vivo studies established that DIM- or cyclopamine-treated ovarian cancer cells under suspensio

225 Both antibody-treated and cyclopamine-treated tongue explants also are smaller tha

226 In Shh(-/-) or cyclopamine-treated wild-type (WT) lung, we found that G

227 Cyclopamine treatment alone significantly reduced anoiki

228 Cyclopamine treatment before stage 20 can rescue the eff

229 In ovo, cyclopamine treatment before the secondary heart field a

230 These data demonstrate that cyclopamine treatment decreases gamma-secretase-mediated

231 In addition, cyclopamine treatment decreases the rate of APP-CTF degr

232 Cyclopamine treatment has the opposite effect, causing a

233 Cyclopamine treatment of murine medulloblastoma cells bl

234 Specifically, cyclopamine treatment reduced APP-C-terminal fragment (C

235 rmacological inhibition of Hh signaling with cyclopamine treatment resulted in nearly complete loss o

236 Using organ cultures and cyclopamine treatment, we showed downregulation of COUP-

237 pear aberrantly at the ventral midline after cyclopamine treatment, while dorsal cell types normally

238 E14 Gli2(-/-) UGS that could be inhibited by cyclopamine treatment.

239 Later (15-20 h) cyclopamine treatments disrupt anterior expression of nk

240 locking Hh signaling both pharmacologically (cyclopamine treatments) and genetically (zebrafish Hh pa

241 ed with the HI+PBS group (P<0.01) and the HI+cyclopamine+UCBMC group (P<0.01).

242 The acid sensitive D-ring of cyclopamine was homologated utilizing a sequence of chem

243 Moreover, the inhibitory effect of cyclopamine was reversed by overexpressing ip6k2.

244 Interestingly, the SMOH inhibitor cyclopamine was unable to uncouple the effects of OPN on

245 Finally, by blocking Shh activity with cyclopamine, we find evidence that continued Shh activit

246 elucidate the early stages of the pathway to cyclopamine, we interrogated a V. californicum RNA-seq d

247 were treated with the Hh receptor antagonist cyclopamine, we observed no effect on tumor burden or bo

248 ose-dependent manner and that the effects of cyclopamine were abolished by adding SHH protein.

249 The activity of FGF2 is unaffected by cyclopamine, which blocks Hedgehog signalling, demonstra

250 ere we show that the plant-derived teratogen cyclopamine, which inhibits the Hh response, is a potent

251 on was obtained using the steroidal alkaloid cyclopamine, which specifically blocks HH signaling.