ライフサイエンスコーパス: cyclopamine

1 iofacial defects by a known human teratogen, cyclopamine.

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

3 ty and better aqueous solubility compared to cyclopamine.

4 l class of hedgehog antagonists derived from cyclopamine.

5 reated with the Hedgehog signaling inhibitor cyclopamine.

6 e Shh signal transduction pathway inhibitor, cyclopamine.

7 ed oligodendrocytes, even in the presence of cyclopamine.

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

9 activity but are structurally distinct from cyclopamine.

10 g antagonism of the Shh signaling pathway by cyclopamine.

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

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

13 and small molecule inhibitors vismodegib and cyclopamine.

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

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

16 cell death in contrast to the Smo inhibitor cyclopamine.

17 o produce verazine, a predicted precursor to cyclopamine.

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

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

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

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

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

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

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

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

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

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

28 Cyclopamine, a potent inhibitor of hedgehog signalling,

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

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

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

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

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

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

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

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

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

38 ahelical bundle in a manner that antagonizes cyclopamine action.

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

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

41 Cyclopamine also can reverse the retention of partially

42 Cyclopamine also suppresses cell growth in vitro and cau

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

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

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

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

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

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

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

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

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

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

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

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

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

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

57 Cyclopamine and 5E1 treatments effectively inhibited cel

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

59 avorable pharmacokinetic profile relative to cyclopamine and compound 2.

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

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

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

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

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

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

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

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

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

69 Cyclopamine and sonic hedgehog (shh) mRNA overexpression

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

113 Unlike cyclopamine, GANT61 induced transient cellular accumulat

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

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

116 The steroidal alkaloid cyclopamine has both teratogenic and antitumor activitie

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

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

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

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

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

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

123 Cyclopamine induced malformation of both foregut and ant

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

125 Shh treatment blocked cyclopamine-induced anoikis.

126 Cyclopamine-induced malformations in chick embryos are a

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

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

129 Cyclopamine inhibited Hh-pathway activation and inductio

130 Cyclopamine inhibited OLP development in cultures of mou

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

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

133 Cyclopamine inhibits hRSV through a novel, Smo-independe

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

135 Cyclopamine instead acts independently of Smo to decreas

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

137 Cyclopamine is a teratogenic steroidal alkaloid that cau

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

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

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

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

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

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

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

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

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

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

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

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

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

151 Cyclopamine-mediated inhibition of the Shh signaling med

152 Cyclopamine-mediated reduction in anoikis resistance was

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

154 tly resistant or have acquired resistance to cyclopamine mimics.

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

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

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

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

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

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

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

162 We show that cyclopamine or synthetic derivatives with improved poten

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

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

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

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

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

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

169 The steroidal alkaloid cyclopamine produces cyclopia and holoprosencephaly when

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

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

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

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

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

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

176 In addition, cyclopamine reduced matrix expression and mitigated fibr

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

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

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

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

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

182 Cyclopamine reveals the capacity of a broad region of th

183 Cyclopamine reversed these effects.

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

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

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

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

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

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

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

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

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

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

194 sonic hedgehog signaling through addition of cyclopamine to cultures.

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

196 Using cyclopamine to inhibit hedgehog signaling, we show that

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

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

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

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

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

202 Somites in cyclopamine-treated embryos show Pax7 expression through

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

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

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

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

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

208 Cyclopamine treatment alone significantly reduced anoiki

209 Cyclopamine treatment before stage 20 can rescue the eff

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

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

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

213 Cyclopamine treatment has the opposite effect, causing a

214 Cyclopamine treatment of murine medulloblastoma cells bl

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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