ライフサイエンスコーパス: PXR

1 PXR ablation inhibited high-fat diet (HFD)-induced obesi

2 PXR activation by PCN in high-fat diet fed mice also inc

3 PXR also contributes to the dysregulation of these proce

4 PXR also has been implicated as a regulator of the growt

5 PXR antagonists 20 and 24 (IC50 = 14 muM), in addition t

6 PXR associates with multiple corepressors that attenuate

7 PXR bound to the FGF19 promoter in both human colon tumo

8 PXR expression was increased, and PXR protein accumulate

9 PXR indirectly activated the IGFBP1 gene by repressing t

10 PXR is a key regulator of pregnancy induced glucuronidat

11 PXR maintains biliary bile acid homeostasis and may be d

12 PXR plays a vital role in the drug metabolism pathway, a

13 PXR prevented CGD via its coordinate regulation of the b

14 PXR-deficient (Nr1i2(-/-)) mice showed a distinctly "lea

15 After administering a PXR agonist, changes in mRNA of most PXR-direct target g

16 ld) and its target, Cyp2b10 (220-fold), in a PXR-dependent manner.

17 Interestingly, a PXR variant with a naturally occurring deletion of a con

18 A luciferase reporter assay on a PXR-transfected HepG2 cell line identified compounds 19-

19 tribromoethanol (Avertin) in vivo, abrogates PXR-mediated resistance to 7-ethyl-10-hydroxycamptotheci

20 determine whether they bind to and activate PXR.

21 mechanism by which these chemicals activate PXR remains unknown.

22 molecule CAR inhibitors that do not activate PXR.

23 Amprenavir efficiently activated PXR and induced PXR target gene expression in vitro and

24 that ketoconazole binds to ligand-activated PXR and antagonizes receptor control of gene expression.

25 -->C mutation and rifampicin (RIF)-activated PXR.

26 Statin-activated PXR scaffolds the protein phosphatase 2C (PP2C) and SGK2

27 sm by which BPA interacts with and activates PXR and examined selected BPA analogues to determine whe

28 Non-phosphorylated SGK2 co-activates PXR-mediated trans-activation of promoters of gluconeoge

29 vity relationship studies of the most active PXR antagonist from the series (compound 20, IC50 = 11 m

30 e variable with similarities of 60%-100% and PXR, CAR, DAX1 and SHP were least conserved among specie

31 metabolism and transport (CYP3A5, ABCB1, and PXR) were analyzed in kidney transplant recipients (1995

32 ned to study the interaction between BPA and PXR.

33 ne whether this gene is regulated by CAR and PXR in vivo, transgenic mice expressing the entire UGT2B

34 ion of CYP1A, CYP2B6 and CYP3A4 (for CAR and PXR), and CYP2C8 (for PXR) gene expression.

35 ement of beta-catenin in the AhR-, CAR-, and PXR-mediated induction of CYP1A, CYP2B6 and CYP3A4 (for

36 nfluent resulted in a decrease in CYP3A4 and PXR expression back to levels observed in subconfluent c

37 ating control cells increased the CYP3A4 and PXR protein levels.

38 egnane X receptor (PXR), in HPH, HepaRG, and PXR-knockout HepaRG cells.

39 PXR expression was increased, and PXR protein accumulated in the nuclei during confluent g

40 onicasterol E represents a FXR modulator and PXR agonist that might hold utility in treatment of live

41 ication between the intestinal symbionts and PXR regulates mucosal integrity through a pathway that i

42 blish PXR as a novel therapeutic target, and PXR antagonists may be used for the prevention and treat

43 We investigated the toxicity and PXR antagonist effect of FLB-12 in vivo.

44 ing male PXR-humanized (hPXR) transgenic and PXR-knock-out (PXR-KO) mice in comparison to wild-type (

45 t for "xenobiotic metabolism signaling" and "PXR/RXR activation" pathways.

46 colon cancer cells in vitro, and attenuates PXR-mediated acetaminophen hepatotoxicity in vivo.

47 scovery of novel bazedoxifene-scaffold-based PXR antagonists inspired by the marine sulfated steroids

48 tabolic liabilities including bioactivation, PXR activation, as well as CYP3A4 induction and inhibiti

49 Both PXR activation and deficiency promote hepatic triglyceri

50 reas an anti-IGFBP1 antibody attenuated both PXR-induced morphological changes and migration in ShP51

51 were resistant to HFD-induced obesity, both PXR-KO and hPXR mice exhibited impaired induction of glu

52 We further show that both PXR and RXRalpha bind to the transcriptional coregulator

53 ligands, the FGF19 promoter was activated by PXR only in cancer cells.

54 CAR, PXR and ESR1 were found to be the most important trans-r

55 that involves the energy status of the cell, PXR regulation, and drug sensitivity.

56 rfering RNA knockdown of HNF4alpha connected PXR-mediated gene regulation with the PXR-induced cellul

57 Decreased PXR binding to the CYP3A4 proximal promoter was found in

58 Activation of AMPK was shown to downregulate PXR activity and, consistent with that, potentiate the r

59 Our results may help to establish PXR as a novel therapeutic target, and PXR antagonists m

60 wildtype (WT) and Pxr-null mice, we examined PXR-mediated regulation of chronic EtOH-induced hepatic

61 epG2-derived ShP51 cells that stably express PXR showed epithelial-mesenchymal transition (EMT)-like

62 Interestingly, control-fed PXR-KO mice exhibited hepatomegaly, hyperinsulinemia, an

63 An FGF21-PXR signaling pathway may be involved in decreased hepat

64 One fluorescent PXR probe is currently commercially available; however,

65 nd CYP3A4 (for CAR and PXR), and CYP2C8 (for PXR) gene expression.

66 hydroxyl groups as hydrogen-bond donors for PXR antagonistic activity.

67 ), in the context of indole, is a ligand for PXR in vivo, and IPA downregulated enterocyte TNF-alpha

68 5 bp, forming a novel DR-(5 n+4) pattern for PXR binding.

69 We now report a novel role for PXR as a critical negative regulator of innate immunity

70 In summary, we discovered an apical role for PXR in regulating innate immunity.

71 ha-IGFBP1 pathway is an essential signal for PXR-induced morphological changes and migration.

72 The GADD45beta gene is a direct target for PXR, eliciting cell signals to regulate various cellular

73 The most frequent PXR DNA-binding motif is the AGTTCA-like direct repeat w

74 Therefore, we generated a roadmap of hepatic PXR bindings in the entire mouse genome [chromatin immun

75 which BPA interacts with and activates human PXR.

76 FL in its function as a high-affinity human PXR ligand.

77 describe a BODIPY FL-vinblastine-based human PXR time-resolved fluorescence resonance energy transfer

78 Upon xenobiotic activation of ectopic human PXR, human hepatocellular carcinoma HepG2 cells were fou

79 its analogues are potent agonists for human PXR (hPXR) but do not affect mouse PXR activity.

80 IPY FL), as a high-affinity ligand for human PXR with a Kd value of 673 nM.

81 ng the expression and functionality of human PXR (hPXR).

82 between the ligand-binding domains of human PXR and RXRalpha.

83 ides a model for exploring the role of human PXR in the metabolic syndrome.

84 s used to successfully test a panel of human PXR ligands.

85 nus carpio) primary hepatocytes to the human PXR agonist rifampicin (RIF) on expression of target gen

86 icularly mycolic acids, crosstalk with human PXR (hPXR) by interacting with its promiscuous ligand bi

87 This study identifies PXR as both a positive and negative regulator of the UGT

88 rmed a mass spectrometric screen to identify PXR-associated proteins.

89 and to avoid the reported species barrier in PXR function, we adopted an in vivo mouse model expressi

90 tagonist binding on the surface or buried in PXR indicates novel aspects to the mechanism of receptor

91 esterol levels in wild-type mice, but not in PXR-deficient mice.

92 The decreased bile acid pool size in PXR-/- mice that received lithogenic diets was associate

93 ic and pharmacokinetic properties, including PXR activation, CYP2C9 inhibition, and CYP3A4 TDI, sever

94 direct target genes correlate with increased PXR binding.

95 BPA and its analogues can also induce PXR target gene expression in human LS180 cells.

96 enavir efficiently activated PXR and induced PXR target gene expression in vitro and in vivo.

97 Finally, vemurafenib strongly induced PXR activity in vitro, but only weakly induced PXR in vi

98 R activity in vitro, but only weakly induced PXR in vivo.

99 These results provide new insights into PXR-mediated cellular responses toward xenobiotics inclu

100 compared our screen results identifying key PXR residues to those predicted by computational methods

101 Cell-based reporter assays, in silico ligand-PXR docking studies, and site-directed mutagenesis were

102 losed, it is not optimal for studying ligand-PXR interactions.

103 HFD)-induced obesity was examined using male PXR-humanized (hPXR) transgenic and PXR-knock-out (PXR-K

104 Amprenavir-mediated PXR activation stimulated the expression of several key

105 structural information was used to modulate PXR affinity for a related CCR1 antagonist compound that

106 MP-activated protein kinase (AMPK) modulates PXR transcriptional activity and that pharmacologically

107 ering a PXR agonist, changes in mRNA of most PXR-direct target genes correlate with increased PXR bin

108 for human PXR (hPXR) but do not affect mouse PXR activity.

109 Altogether, although the mouse PXR promotes HFD-induced obesity, the hPXR mouse carries

110 ligand specificities between human and mouse PXRs, the role of PXR in high fat diet (HFD)-induced obe

111 her xenobiotic or hormonal receptors, namely PXR, AHR, and vitamin D receptor, which regulate major x

112 ne such inhibitor, CINPA1 (CAR inhibitor not PXR activator 1), capable of reducing CAR-mediated trans

113 Of note, PXR deficiency suppressed these changes and steatosis.

114 ation and downregulation of lipin-1, a novel PXR target gene.

115 lpha but not 10 other NRs in vivo, while NRs PXR, FXRalpha, Rev-Erbalpha appear to bind adjacent to H

116 tor of CYP3A4 Furthermore, decreased nuclear PXR was observed in mouse liver and Huh7 cells after FGF

117 Wild-type, PXR-null (PXR-/-), and CGD-sensitive C57L mice were placed on a li

118 Activation of PXR by BPA may explain some of the adverse effects of BP

119 Here we report that the activation of PXR by pregnenolone 16alpha-carbonitrile (PCN) in AKR/J

120 Activation of PXR was found to be sufficient to enhance the neoplastic

121 Activation of PXR, but not of the closely related constitutive androst

122 CAR inverse-agonists are also activators of PXR, rendering them mechanistically counterproductive in

123 This review highlights areas of PXR regulation that require further clarification and su

124 The metabolic benefit of PXR ablation was opposite to the reported prodiabetic ef

125 Mechanistically, the metabolic benefits of PXR ablation were associated with the inhibition of c-Ju

126 , we showed that p53 inhibits the binding of PXR to the CYP3A4 promoter.

127 The ob/ob mice deficient of PXR showed increased oxygen consumption and energy expen

128 of CYP3A4, and siRNA-mediated knock-down of PXR in confluent cells resulted in decreased CYP3A4 expr

129 4 muM), in addition to the downregulation of PXR expression, exhibited inhibition of PXR-induced CYP3

130 work provides the first in vivo evidence of PXR DNA-binding signatures in the mouse genome, paving t

131 Evolution of PXR and CAR exhibited unexpected multiple patterns and t

132 pathway, and a comprehensive examination of PXR-associated proteins will provide greater insight int

133 tiating hESCs, and stable over-expression of PXR in hepatic-induced hESCs failed to enhance expressio

134 -hybrid screen that examined mutant forms of PXR.

135 ese results verify the important function of PXR in lipid and energy metabolism and suggest that PXR

136 In the past several years, the function of PXR in the regulation of xenobiotic metabolism has been

137 we have now demonstrated a novel function of PXR, that of eliciting p38 mitogen-activated protein kin

138 erstanding of the nonxenobiotic functions of PXR that can be explored for relevant therapeutic applic

139 ts uncover SLC13A5 as a novel target gene of PXR and may contribute to drug-induced steatosis and met

140 ous cancer cells indicates the importance of PXR as a drug target for countering multidrug resistance

141 lls is caused by the endogenous induction of PXR as a result of cell-cell contact inhibited prolifera

142 n of PXR expression, exhibited inhibition of PXR-induced CYP3A4 expression, which illustrates their p

143 al hUGT1 hepatocytes through interruption of PXR by small interfering RNA.

144 Loss of PXR sensitized mice to lithogenic diet-induced CGD, char

145 However, the molecular mechanism of PXR-mediated activation of ethanol (EtOH)-induced steato

146 Modulation of PXR transactivation has revealed the selective and orall

147 The overexpression of PXR in various cancer cells indicates the importance of

148 residues within the ligand-binding pocket of PXR that constitute points of interaction with amprenavi

149 itable for development as chemical probes of PXR function as well as potential PXR-directed therapeut

150 h PXR; enhancing RIF-mediated recruitment of PXR to the -82T-->C harboring CYP2B6 promoter; and loopi

151 dogenous, non-ligand-dependent regulation of PXR and CYP3A4, possibly of physiologic and pharmacologi

152 f BPA and its analogues on the regulation of PXR target genes in human LS180 cells.

153 site that are associated with regulation of PXR-mediated SLC13A5 induction.

154 f the cell cycle and a negative regulator of PXR, was more highly expressed in proliferating control

155 as been extensively studied, and the role of PXR as a xenobiotic sensor has been well established.

156 es between human and mouse PXRs, the role of PXR in high fat diet (HFD)-induced obesity was examined

157 disease and demonstrate a potential role of PXR in mediating the adverse effects of HIV PIs in human

158 e uncovered an unexpected endobiotic role of PXR in obesity and type 2 diabetes.

159 These recent discoveries of the role of PXR in the physiologic and pathophysiologic conditions o

160 discovered previously unidentified roles of PXR in inflammatory response, cell proliferation, and ce

161 ther understanding the multifaceted roles of PXR in liver.

162 define the antagonist binding surface(s) of PXR, we developed a novel assay to identify key amino ac

163 Yeast high throughput screens of PXR mutants define a unique region for ketoconazole bind

164 12)] that antagonizes the activated state of PXR with limited effects on other related nuclear recept

165 The unique structure of PXR allows the binding of many drugs and drug leads to i

166 Three different co-crystal structures of PXR LBD with Adnectin-1 and CCR1 (CC chemokine receptor-

167 The structures of PXR with Adnectin-1 reveal specificity of Adnectin-1 in

168 ization chaperones to generate structures of PXR with compounds of interest.

169 f antagonist binding sites on the surface of PXR and suggest new avenues to regulate this receptor fo

170 Gln-272, and Phe-264 on the AF-2 surface of PXR.

171 A5 gene is a novel transcriptional target of PXR, and altered expression of SLC13A5 affects lipid acc

172 Thus, relatively selective targeting of PXR by antagonists is feasible and warrants further inve

173 f HNF4alpha to loop the promoter and that of PXR to repress the promoter activity.

174 her, these data advance our understanding of PXR, the master regulator of drug metabolism gene expres

175 assay to identify key amino acid residues on PXR based on a yeast two-hybrid screen that examined mut

176 manized (hPXR) transgenic and PXR-knock-out (PXR-KO) mice in comparison to wild-type (WT) mice.

177 synthetic strategy, and rifaximin, a potent PXR agonist, demonstrated that conicasterol E is an FXR

178 contrast with mammals, where CTZ is a potent PXR-agonist.

179 mprenavir, a widely used HIV PI, as a potent PXR-selective agonist.

180 probes of PXR function as well as potential PXR-directed therapeutics.

181 Collectively our data indicate potential PXR involvement in regulating selected genes involved in

182 line identified compounds 19-24 as promising PXR antagonists.

183 Compared with ketoconazole, a prototypical PXR antagonist, FLB-12 is significantly less toxic to he

184 The prototypical PXR activator rifampicin markedly induced the mRNA and p

185 ed the cloning of the human nuclear receptor PXR and demonstrated that it mediates CYP3A induction.

186 The human nuclear xenobiotic receptor PXR recognizes a range of potentially harmful drugs and

187 benz yl)oxime (CITCO)], pregnane X receptor (PXR) [rifampicin], and peroxisome proliferator-activated

188 inds to and antagonizes pregnane X receptor (PXR) activation.

189 Upon treatment with the pregnane X receptor (PXR) activator rifampicin (RIF), human hepatocellular ca

190 ic sensors, such as the pregnane X receptor (PXR) and constitutive androstane receptor (CAR), may und

191 Statins utilize pregnane X receptor (PXR) and serum/glucocorticoid regulated kinase 2 (SGK2)

192 estinal flora, activate pregnane X receptor (PXR) and subsequent CYP3A4 and CYP2C9 expression in hPSC

193 tane receptor (CAR) and pregnane X receptor (PXR) are xenobiotic sensors that enhance the detoxificat

194 the xenobiotic receptor pregnane X receptor (PXR) has a role in pathogenesis of CGD.

195 s heterodimeric partner pregnane X receptor (PXR) in mice.

196 clear factor-4alpha, or pregnane X receptor (PXR) in PHHs.

197 The pregnane X receptor (PXR) is a key regulator of xenobiotic metabolism and dis

198 The pregnane X receptor (PXR) is a master regulator of xenobiotic clearance and i

199 The pregnane X receptor (PXR) is a master regulator of xenobiotic metabolism, and

200 Pregnane X receptor (PXR) is a nuclear receptor considered to be a master xen

201 The human pregnane X receptor (PXR) is a promiscuous nuclear receptor that functions as

202 Pregnane X receptor (PXR) is a xenobiotic receptor that regulates the detoxif

203 The nuclear receptor pregnane X receptor (PXR) is activated by a range of xenochemicals, including

204 Pregnane X receptor (PXR) is known to function as a xenobiotic sensor to regu

205 The nuclear pregnane X receptor (PXR) plays a central role in regulating xenobiotic metab

206 In mammals the pregnane X receptor (PXR) plays a key role in the regulation of a suite of ge

207 ane receptor (CAR), and pregnane X receptor (PXR) regulate and alter the metabolism of xenobiotic sub

208 The human pregnane X receptor (PXR) regulates genes involved in drug metabolism and dis

209 The pregnane X receptor (PXR) regulates the metabolism and excretion of xenobioti

210 By employing a pregnane X receptor (PXR) reporter gene assay to prioritize compounds for fur

211 Pregnane X receptor (PXR) was originally characterized as a transcription fac

212 ear localization of the pregnane X receptor (PXR), a key transcriptional regulator of CYP3A4 Furtherm

213 Pregnane X receptor (PXR), a member of the NR1I nuclear receptor family, acts

214 xpression levels of the pregnane X receptor (PXR), a nuclear receptor most similar to CAR in primary

215 n shown to activate the pregnane X receptor (PXR), a nuclear receptor that functions as a master regu

216 nt reports suggest that pregnane X receptor (PXR), a xenobiotic nuclear receptor important for defens

217 Pregnane X receptor (PXR), acting as a xenobiotic-activated transcription fac

218 AhR), activation of the pregnane X receptor (PXR), activation of the estrogen receptor (ER), adaptive

219 The pregnane X receptor (PXR), along with its sister receptor constitutive andros

220 ells overexpressing the pregnane X receptor (PXR), but not in hepatoma cells in which PXR was knocked

221 targets of hCAR and the pregnane X receptor (PXR), in HPH, HepaRG, and PXR-knockout HepaRG cells.

222 le of nuclear receptor, pregnane X receptor (PXR), in M. tuberculosis infection in human monocyte-der

223 ng the nuclear receptor pregnane X receptor (PXR), which acts as a xenobiotic sensor to regulate xeno

224 Here, using a pregnane X receptor (PXR)-humanized mouse model, we found that co-treatment w

225 coid, progestogenic and pregnane X receptor (PXR)-like activities (mug standard-EQ/g of sorbent range

226 , suggesting that other pregnane X receptor (PXR)-regulated pathways may contribute more significantl

227 the xenobiotic sensor, pregnane X receptor (PXR).

228 in a process involving pregnane X receptor (PXR).

229 The pregnane X receptor (PXR, NR1I2) is a xenobiotic-sensing nuclear receptor tha

230 Pregnane X receptor (PXR, NR1I2), a member of the superfamily of nuclear rece

231 Recently, the pregnane X receptor (PXR, NR1I2), initially characterized as a xenobiotic sen

232 e that wild-type p53 can negatively regulate PXR by physically associating with it.

233 quired but not sufficient for p53 to repress PXR activity.

234 Upon activation by RIF, PXR indirectly interacted with the enhancer, decreasing

235 cancer growth in the presence of a specific PXR ligand results from tumor-specific induction of FGF1

236 directed synthesis of a relatively specific PXR inhibitor has remained elusive.

237 conazole genetically interacts with specific PXR surface residues.

238 This gluconeogenic statin-PXR-SGK2 signal is not present in mice, in which statin

239 Here, the novel statin/PXR/SGK2-mediated signaling pathway has now been charact

240 mal cLogD values and the discovery of subtle PXR SAR that was not lipophilicity dependent.

241 hich illustrates their potential to suppress PXR-regulated phase-I drug metabolism.

242 s, in particular the glucocorticoids, target PXR as a positive regulator of human glucuronidation.

243 In this study, we demonstrate that PXR augments M. tuberculosis survival inside the host ma

244 These data demonstrated that PXR regulated pathogen-induced inflammation and host def

245 We determined that PXR is expressed in liver, acts through a DNA response e

246 These structures establish that PXR and RXRalpha form a heterotetramer unprecedented in

247 These findings establish that PXR signaling contributes to ALD development and suggest

248 Given our finding that PXR activation by rifampicin (RIF) represses the estroge

249 It is now clear, however, that PXR plays many other roles in addition to its xenobiotic

250 These results indicate that PXR activates the GADD45beta gene, increasing p38 MAPK p

251 Recent studies indicate that PXR may also play an important role in the regulation of

252 We observed that PXR activity was induced under high-glucose conditions.

253 unoprecipitation (ChIP) assays revealed that PXR activation by RIF disrupted enhancer-promoter commun

254 l-based reporter and ChIP assays showed that PXR targeted the distal enhancer of the HNF4alpha P1 pro

255 tributes to ALD development and suggest that PXR antagonists may provide a new approach for ALD thera

256 lipid and energy metabolism and suggest that PXR represents a novel therapeutic target for prevention

257 The PXR ligand rifampicin further increased the expression o

258 ression of all target genes measured and the PXR antagonist ketoconazole (KET) inhibited responses of

259 MP may be explained, at least partly, by the PXR-dependent transcriptional inhibition of ATX expressi

260 First the PXR-responsive enhancer was delineated to a 100 bp seque

261 In C57L mice given the PXR agonist, pregnenolone-16alpha-carbonitrile, or the h

262 ss than 0.2% of the biological effect in the PXR activation, adaptive stress response, and fish embry

263 horylation-deficient mutation (S350A) in the PXR protein significantly induced the CYP3A4 transcripti

264 FLB-12 significantly inhibits the PXR-activated loss of righting reflex to 2,2,2-tribromoe

265 In an independent model, introducing the PXR(-/-) allele into the ob/ob background also improved

266 C harboring CYP2B6 promoter; and looping the PXR-bound distal phenobarbital-responsive enhancer modul

267 ,-dichloropyridyloxy)] (TCPOBOP) but not the PXR ligand pregnenolone 16alpha-carbonitrile.

268 th higher affinity when they are part of the PXR/RXRalpha heterotetramer complex than they do when ea

269 d for by the inhibitory effect of LXR on the PXR-responsive transactivation of Cyp3a11.

270 n type III domain ((10)Fn3), that target the PXR ligand binding domain (LBD) interactions with the st

271 s cell system, we demonstrated here that the PXR-HNF4alpha-IGFBP1 pathway is an essential signal for

272 d not interact with p53, indicating that the PXR-p53 interaction is specific.

273 nction" mutants that were "resistant" to the PXR antagonist effects of ketoconazole.

274 clear factor 4alpha (HNF4alpha) bound to the PXR-responsive enhancer, and activated the enhancer by l

275 rized the molecular mechanism underlying the PXR-mediated repression of the HNF4alpha gene.

276 nected PXR-mediated gene regulation with the PXR-induced cellular responses, showing that the knockdo

277 Furthermore, we were able to show that this PXR-mediated phenotype required FGF19 signaling.

278 t that modulation of bioavailability through PXR-mediated regulation of drug transporters (e.g., by o

279 toxin protoporphyrin IX in the liver through PXR-mediated alteration of the heme biosynthesis pathway

280 Thus, PXR and p53 appear to play important yet opposing roles

281 Thus, PXR represses human SULT1E1, possibly attenuating the in

282 Thus, PXR serves to repress UGT1A1 gene expression during deve

283 ues that are involved in binding of SRC-1 to PXR.

284 l to evaluate whether lead compounds bind to PXR.

285 g to evaluate whether lead compounds bind to PXR.

286 K activation exhibits an inverse relation to PXR activity.

287 azole and a 10-fold induction in response to PXR agonist rifampicin.

288 both cell types proliferated in response to PXR ligands, the FGF19 promoter was activated by PXR onl

289 Wild-type, PXR-null (PXR-/-), and CGD-sensitive C57L mice were plac

290 ne a molecular mechanism that might underlie PXR-driven colon tumor growth and malignancy.

291 Employing reverse genetics, where PXR has been genetically deleted, hUGT1/Pxr(-/-) mice sh

292 nsitivity to chemotherapeutic drugs, whereas PXR contributes to chemoresistance in many cancer cells.

293 WT mice showed greater weight gain, whereas PXR-KO mice gained less weight due to their resistance t

294 or (PXR), but not in hepatoma cells in which PXR was knocked down.

295 or suppressor protein p53 can associate with PXR and downregulate its activity.

296 icasterol E is an FXR modulator endowed with PXR agonistic activity.

297 such synergism by directly interacting with PXR; enhancing RIF-mediated recruitment of PXR to the -8

298 e p53 by competing with its interaction with PXR, suggesting that protein-protein interaction is requ

299 f-function p53 mutant (R175H) interacts with PXR but does not repress its activity.

300 Together with pregnane X (PXR) and aryl hydrocarbon (AHR) receptors, it is referre