ライフサイエンスコーパス: CYP2D6

1 tic metabolizing enzyme cytochrome P450 2D6 (CYP2D6).

2 ntibody type 1 targeting cytochrome P4502D6 (CYP2D6).

3 l as non-MHC genes (IL-1RA, IL-6, IL-10, and CYP2D6).

4 nd replace it with allelic variants of human CYP2D6.

5 uration in clinically relevant genes such as CYP2D6.

6 ght be in strong linkage disequilibrium with CYP2D6.

7 tions of P-glycoprotein, villin, CYP1A1, and CYP2D6.

8 potentiation of HNF4alpha transactivation of CYP2D6.

9 tion of HNF4alpha-induced transactivation of CYP2D6.

10 s and also in cells expressing mitochondrial CYP2D6.

11 predominantly endoplasmic reticulum-targeted CYP2D6.

12 ferentiated neurons expressing mitochondrial CYP2D6.

13 sing the two frequent human protein isoforms CYP2D6.1 and CYP2D6.2 and an as yet undescribed variant

14 frequent human protein isoforms CYP2D6.1 and CYP2D6.2 and an as yet undescribed variant of this enzym

15 Immune responses to CYP2D6(245-254) were the strongest both at diagnosis and

16 CD8 T cell targets on CYP2D6-in particular CYP2D6(245-254)-may be the focus of novel immune interve

17 g for cytochromes P450 (CYPs) 2D6 (CYP2D6*4, CYP2D6*3, CYP2D6*5, and CYP2D6*6) and 2E1 (cl/c2), multi

18 CYP2D6 (*4 and *6) and CYP3A5 (*3) genotypes were determ

19 Women with the CYP2D6 *4/*4 genotype had worse relapse-free time (RF-ti

20 In the multivariate analysis, women with the CYP2D6 *4/*4 genotype still tended to have worse RFS (ha

21 n tamoxifen-treated patients, women with the CYP2D6 *4/*4 genotype tend to have a higher risk of dise

22 Significant within-family association of CYP2D6*4 alleles and AS was demonstrated.

23 r the most frequent poor metabolizer allele (CYP2D6*4) was not associated with increased susceptibili

24 enes coding for cytochromes P450 (CYPs) 2D6 (CYP2D6*4, CYP2D6*3, CYP2D6*5, and CYP2D6*6) and 2E1 (cl/

25 chromes P450 (CYPs) 2D6 (CYP2D6*4, CYP2D6*3, CYP2D6*5, and CYP2D6*6) and 2E1 (cl/c2), multidrug resis

26 CYPs) 2D6 (CYP2D6*4, CYP2D6*3, CYP2D6*5, and CYP2D6*6) and 2E1 (cl/c2), multidrug resistance 1 (MDR1

27 Cytochrome P450 2D6 (CYP2D6), a major drug-metabolizing enzyme, is responsibl

28 For CYP2D6, a clear relationship between polar surface area

29 rectly position a range of substrates in the CYP2D6 active site with the known sites of metabolism ab

30 The measured CYP3A4 and CYP2D6 activities also failed to predict the susceptible

31 CYP2D6 activity can also be reduced by concomitant use o

32 yb5 can be a major determinant of CYP3A4 and CYP2D6 activity in vivo, with a potential impact on the

33 xylase activity and that HNF4alpha regulates CYP2D6 activity in vivo.

34 ky had genotypes associated with extremes in CYP2D6 activity that may have affected their response to

35 gest that women who carry one or two variant CYP2D6 alleles that encode enzymes with null or reduced

36 ent ways: (1) rapid discrimination of common CYP2D6 alleles, (2) high-resolution haplotyping for asso

37 e or more of the numerous drugs sensitive to CYP2D6 allelic composition.

38 ust approach for the expression of different CYP2D6 allelic variants in transgenic mice and thus can

39 We also show that WBC express CYP2D6, an enzyme capable of synthesizing morphine from

40 rphisms in the drug-metabolizing enzyme gene CYP2D6 and a number of linked microsatellites that is bo

41 of seven simple nucleotide polymorphisms in CYP2D6 and also to assay repeat number variation at five

42 Weak linkage was also demonstrated between CYP2D6 and AS.

43 achieved different effects in patients with CYP2D6 and beta1-receptor polymorphisms.

44 yrosol formation and supported findings that CYP2D6 and CYP2A6 mediated this reaction.

45 n the x-ray crystal structure coordinates of CYP2D6 and CYP2C8 showed that despite lacking the N-term

46 Human breast CYP2D6 and CYP2D7P (from a pseudogene) mRNAs were previo

47 s of blood THMs, including factors affecting CYP2D6 and CYP2E1 activity.

48 man CYP450 proteins CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 are the major drug-metabolizing isofor

49 s with baculosomes further demonstrated that CYP2D6 and CYP3A4 could transform tyrosol into hydroxyty

50 out affinity for the major drug-metabolizing CYP2D6 and CYP3A4 enzymes and CYP21A2, with the latter r

51 2A6 and CYP2E1) or this region and alpha2-3 (CYP2D6 and CYP3A4) and suggested variation in the affini

52 imilarity and genetic recombinations between CYP2D6 and evolutionarily related pseudogenes CYP2D7 and

53 phase clinically important haplotypes at the CYP2D6 and HLA loci.

54 cation, deletion and fusion events involving CYP2D6 and its evolutionarily related cousin CYP2D7.

55 s no association between any polymorphism of CYP2D6 and Parkinson's disease, but two of 10 dinucleoti

56 egulation of P450 expression (especially for CYP2D6) and more complex trans-regulation of P450 activi

57 compounds and their metabolites from CYP1A2, CYP2D6, and CYP3A4 and a mixture of the three P450s desi

58 P enzymes including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 and the crucial steroidogenic enzymes

59 major enzymes detected were CYP1B1, CYP2B6, CYP2D6, and CYP3A4 with mean values of 2.5, 2.6, 2.7, an

60 not inhibited by an anti-CYP2C11 or an anti-CYP2D6 antibody.

61 opaminergic neurons expressing mitochondrial CYP2D6 are fully capable of activating the pro-neurotoxi

62 had identified a region 115 kb downstream of CYP2D6 as enhancer for CYP2D6, containing two completely

63 riate HLA-DR molecule and recognition of the CYP2D6 autoantigenic sequence were critical to the syner

64 riate HLA-DR molecule and recognition of the CYP2D6 autoantigenic sequence were critical to the syner

65 Tam metabolism by CYP2D6 coexpressed with P450 reductase in a baculovirus

66 115 kb downstream of CYP2D6 as enhancer for CYP2D6, containing two completely linked single nucleoti

67 so analyzed commercial DNA samples for their CYP2D6 copy numbers and confirmed that our results were

68 n-metabolizing enzymes GSTT1, GSTM1, CYP1A1, CYP2D6, CYP2C19, SULT1A1, and NQO1 were previously deter

69 We sequenced CYP2D6, CYP2C8, CYP2C9, CYP3A4, and SLCO1B1 and tested 7

70 n metabolizing-enzyme genes (such as CYP3A4, CYP2D6, CYP2C9, CYP1A2, CYP2E1 and UGT1A4) in THLE-2 cel

71 , membrane-associated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 are responsi

72 ot only a mixed inhibitor of CYP2B6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4, but also a non-competitive in

73 ha-thujone by human CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 occurs with up to 80% C-4 met

74 50 enzymes (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A5).

75 enzymes analysed in these three groups were: CYP2D6, CYP2E1, NAD(P)H-menadione reductase, glutathione

76 o detectable effect on expression of CYP1A1, CYP2D6, cytochrome b5, liver or intestinal fatty acid bi

77 to, or within, the cytochrome P450 2D6 gene (CYP2D6, debrisoquine hydroxylase) located at chromosome

78 The patients with CYP2D6 deficiency also appeared more likely to experienc

79 Twelve of the patients were CYP2D6 deficient, and four carried the *1Xn or *2Xn alle

80 it is difficult to predict pathways of human CYP2D6-dependent drug metabolism on the basis of animal

81 mice and thus can help to evaluate potential CYP2D6-dependent interindividual differences in drug res

82 ene (GSTM1) or the cytochrome P450 2D6 gene (CYP2D6) did not show a significant association with the

83 bstrates of a major drug-metabolizing enzyme CYP2D6 display increased elimination during pregnancy, b

84 sessment of the consequences of differential CYP2D6 drug metabolism, we have developed a novel straig

85 CYP2D6 gene, could affect the disposition of CYP2D6 drug substrates.

86 To characterize the CYP2D6 enhancer element, we applied chromatin conformati

87 cause large inter-individual variability in CYP2D6 enzyme activity and are currently used as biomark

88 s highly polymorphic gene which encodes the (CYP2D6) enzyme, involved in the metabolism of 20-25% of

89 to have a strong DDI through the CYP3A4 and CYP2D6 enzymes, respectively.

90 Mitochondrial CYP2D6 expressing Neuro-2A cells produced higher levels

91 sed SHP (by approximately 50%) and decreased CYP2D6 expression (by 1.5-fold) in Tg-CYP2D6 mice, the m

92 Several novel SNPs associated with CYP2D6 expression and enzyme activity were validated in

93 uced cholestasis increases SHP and represses CYP2D6 expression in Tg-CYP2D6 mice in part through ERal

94 The rate of deficiency in CYP2D6 expression in these Caucasian state psychiatric h

95 YP2D6) mice as an animal model where hepatic CYP2D6 expression is increased during pregnancy.

96 However, the enhancer effect on CYP2D6 expression, and the causative variant, remained t

97 the previously identified enhancer region in CYP2D6 expression, expanding the number of candidate var

98 th the enhancer element and SNP rs5758550 on CYP2D6 expression, supporting consideration of rs5758550

99 a high dose led to 2- to 3-fold decreases in CYP2D6 expression.

100 e effects of estrogen-induced cholestasis on CYP2D6 expression.

101 P knockdown led to a significant increase in CYP2D6 expression.

102 alpha), a known transcriptional activator of CYP2D6 expression.

103 Patients found to be CYP2D6 extensive metabolizers (EM) remained on 20 mg and

104 coadministered with tamoxifen interfere with CYP2D6 function, thereby reducing endoxifen concentratio

105 6 substrates, a mouse line carrying both the CYP2D6 gene and the HNF4alpha conditional mutation was g

106 Single nucleotide polymorphisms in the CYP2D6 gene are not uncommon, and some alleles code for

107 ple, we tested an 890 kb region flanking the CYP2D6 gene associated with poor drug-metabolizing activ

108 abolism of a natural toxin or antigen by the CYP2D6 gene may increase susceptibility to AS.

109 Association of alleles of the CYP2D6 gene was examined by both case-control and within

110 a transgenic mouse line expressing the human CYP2D6 gene was generated.

111 Allelic variants of the CYP2D6 gene, a member of the cytochrome P450 gene superf

112 known to regulate in vitro expression of the CYP2D6 gene, could affect the disposition of CYP2D6 drug

113 The complete wild-type CYP2D6 gene, including its regulatory sequence, was micr

114 to extensively characterize variation in the CYP2D6 gene.

115 rated tissues, all of which showed excellent CYP2D6 genotype agreement.

116 demiology studies on the association between CYP2D6 genotype and breast cancer recurrence report wide

117 no clinically important association between CYP2D6 genotype and breast cancer survival in tamoxifen-

118 the first algorithm to computationally infer CYP2D6 genotype at basepair resolution from HTS data.

119 CYP2D6 genotype did not predict treatment outcome for ei

120 Accounting for CYP2D6 genotype status did not change these estimates.

121 Thirty-one studies of the association of CYP2D6 genotype with breast cancer survival have yielded

122 Endoxifen clearance was unaffected by CYP2D6 genotype.

123 genic metabolite, are reduced in women whose CYP2D6 genotypes confer poor enzyme function.

124 ata on the frequency of cytochrome P450-2D6 (CYP2D6) genotypes in state psychiatric hospital patients

125 CYP2D6 genotyping is recommended prior to treatment deci

126 We argue that a recommendation for CYP2D6 genotyping of candidates for tamoxifen therapy, a

127 n, supporting consideration of rs5758550 for CYP2D6 genotyping panels to yield more accurate phenotyp

128 We examined the feasibility of using CYP2D6 genotyping to determine optimal tamoxifen dose an

129 s of specific sequences of p53, p16, CYP1A1, CYP2D6, GSTM1 and GSTM3 were performed independently on

130 olizing enzymes such as cytochrome P450 2D6 (CYP2D6) has been postulated to underlie antidepressant i

131 CYP2D6 have been intensively studied, but the role of CY

132 Associations with CYP2D6 have either been absent altogether or have involv

133 d debrisoquine were significantly altered in CYP2D6-HBN mice, the AUC0-8 h being increased approximat

134 olol alpha-hydroxylation were observed using CYP2D6-HBN microsomes, indicating a significant role for

135 expression of a known positive regulator of CYP2D6, hepatocyte nuclear factor 4alpha (HNF4alpha), di

136 data presented in this study show that only CYP2D6 humanized mice but not wild-type mice display sig

137 fe significantly reduced (6.9 +/- 1.6 h), in CYP2D6 humanized mice compared with wild-type animals (1

138 of HNF4alpha, DEB 4-hydroxylase activity in CYP2D6 humanized mice decreased more than 50%.

139 The CYP2D6 humanized mice represent an attractive model for

140 e liver, intestine, and kidney from only the CYP2D6 humanized mice.

141 Here, we introduce CYP2D6-humanized (Tg-CYP2D6) mice as an animal model whe

142 in the livers of pregnant versus nonpregnant CYP2D6-humanized (tg-CYP2D6) mice was compiled via micro

143 In CYP2D6-humanized transgenic (Tg-CYP2D6) mice, cholestasi

144 d to investigate whether T-regs specific for CYP2D6 immunodominant regions and restricted by the appr

145 d to investigate whether T-regs specific for CYP2D6 immunodominant regions and restricted by the appr

146 uide for the use of medications that inhibit CYP2D6 in patients administered tamoxifen.

147 se in the expression and activity of hepatic CYP2D6 in Tg-CYP2D6 mice.

148 CD8 T cell targets on CYP2D6-in particular CYP2D6(245-254)-may be the focus of

149 d KLF9 expression is in part responsible for CYP2D6 induction during pregnancy via the potentiation o

150 cription factors potentially responsible for CYP2D6 induction during pregnancy, a panel of genes diff

151 owing high in vitro permeability and lacking CYP2D6 inhibition as main optimization parameters.

152 ico ADMET models for Caco-2 permeability and CYP2D6 inhibition were also successfully applied for thi

153 prove compound aqueous solubility and reduce CYP2D6 inhibition, which led to the discovery of compoun

154 achieve the therapeutic effect regardless of CYP2D6 inhibition.

155 amage, which is effectively prevented by the CYP2D6 inhibitor quinidine.

156 imary dopaminergic neurons was attenuated by CYP2D6 inhibitor, quinidine, and also partly by monoamin

157 CYP2D6 is a highly polymorphic human gene responsible fo

158 CYP2D6 is expressed on the hepatocyte surface, and it ca

159 CYP2D6 is highly polymorphic gene which encodes the (CYP

160 onsistent with our previous observation that CYP2D6 is responsible for the metabolic activation of ta

161 CYP2D6 is the key enzyme responsible for the conversion

162 CYP2D6 is the key enzyme responsible for the generation

163 ports of associations between alleles of the CYP2D6 locus (nearby on 22q13) and IPD, although inconsi

164 vided informed consent were genotyped at the CYP2D6 locus during their hospital stay.

165 ification from loss of heterozygosity at the CYP2D6 locus.

166 on of CYP3A4-mediated triazolam turnover and CYP2D6-mediated bufuralol and debrisoquine turnover on a

167 insights into mechanisms underlying altered CYP2D6-mediated drug metabolism during pregnancy, laying

168 and showed greatly reduced susceptibility to CYP2D6-mediated metabolism.

169 pharmacology, toxicology, and physiology of CYP2D6-mediated metabolism.

170 ity that may have affected their response to CYP2D6 medications.

171 ly to experience side effects in response to CYP2D6 medications.

172 ecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-l

173 tudies demonstrated that women with impaired CYP2D6 metabolism have lower endoxifen concentrations an

174 ides substantial drug exposure unaffected by CYP2D6 metabolism, acceptable toxicity, and promising an

175 moxifen dosing in patients with intermediate CYP2D6 metabolism.

176 king its metabolic liability associated with CYP2D6 metabolism.

177 d are currently used as biomarker to predict CYP2D6 metabolizer phenotype.

178 nes cover a wide spectrum of different human CYP2D6 metabolizer phenotypes.

179 CYP2D6 metabolizes nearly 25% of clinically used drugs.

180 KLF9 to CYP2D6 promoter in the livers of tg-CYP2D6 mice during pregnancy.

181 es SHP and represses CYP2D6 expression in Tg-CYP2D6 mice in part through ERalpha transactivation of S

182 In transgenic (Tg)-CYP2D6 mice, SHP knockdown led to a significant increase

183 reased CYP2D6 expression (by 1.5-fold) in Tg-CYP2D6 mice, the magnitude of differences being much sma

184 ression and activity of hepatic CYP2D6 in Tg-CYP2D6 mice.

185 reased hepatic levels during pregnancy in Tg-CYP2D6 mice.

186 Here, we introduce CYP2D6-humanized (Tg-CYP2D6) mice as an animal model where hepatic CYP2D6 exp

187 nant versus nonpregnant CYP2D6-humanized (tg-CYP2D6) mice was compiled via microarray experiments fol

188 In CYP2D6-humanized transgenic (Tg-CYP2D6) mice, cholestasis triggered by administration of

189 on-functional alleles of the cytochrome P450 CYP2D6 might be poor candidates for adjuvant tamoxifen t

190 rgeting suspected enhancer regions decreased CYP2D6 mRNA expression by 70%, only upon deletion of the

191 ith dinucleotide repeat markers mapping near CYP2D6 on ch22q13.

192 The cytochrome P450 mono-oxygenase gene, CYP2D6 on chromosome 22q13 (ch22q13), has been inconsist

193 address this, we crossed mice humanized for CYP2D6 or CYP3A4 with mice carrying a hepatic Cyb5 delet

194 y the polymorphic cytochrome P-450 2D6 gene (CYP2D6), oxidizes tamoxifen to its most active metabolit

195 city was obtained by coculturing T-regs with CYP2D6-peptide-loaded semimature dendritic cells (smDCs)

196 city was obtained by coculturing T-regs with CYP2D6-peptide-loaded semimature dendritic cells (smDCs)

197 Binding affinity of CYP2D6 peptides to HLA-A2 was predicted by the algorithm

198 Seven CYP2D6 peptides with high HLA-A2 binding affinity coloca

199 We examined the association between CYP2D6 polymorphisms and Parkinson's disease in a case-c

200 ot occur at concentrations observed in human CYP2D6 poor metabolizers.

201 sults from deletion and mutation analysis of CYP2D6 promoter activity identified a KLF9 putative bind

202 that KLF9 itself is a weak transactivator of CYP2D6 promoter but significantly enhances CYP2D6 promot

203 ssay showed increased recruitment of KLF9 to CYP2D6 promoter in the livers of tg-CYP2D6 mice during p

204 However, HNF4alpha recruitment to CYP2D6 promoter increased at term pregnancy, accompanied

205 f CYP2D6 promoter but significantly enhances CYP2D6 promoter transactivation by hepatocyte nuclear fa

206 decreases in the recruitment of HNF4alpha to CYP2D6 promoter.

207 , SHP repressed HNF4alpha transactivation of CYP2D6 promoter.

208 the transactivation of cytochrome P450 2D6 (CYP2D6) promoter by hepatocyte nuclear factor (HNF) 4alp

209 si-synthetic data set in which data from the CYP2D6 region are embedded within simulated data on 100K

210 effectors targeting identical or overlapping CYP2D6 regions.

211 effectors targeting identical or overlapping CYP2D6 regions.

212 rder to probe the potential for differential CYP2D6 regulation in lung normal tissue and tumors.

213 We investigated CYP2D6-specific CD8 T cell human leukocyte antigen (HLA)

214 Conclusion: HLA-A2-restricted, CYP2D6-specific CD8 T cell immune responses vary accordi

215 CYP2D6-specific CD8 T cell reactivity was tested at diag

216 Intensity of CYP2D6-specific CD8 T cell responses correlated with dis

217 nd frequency of circulating and intrahepatic CYP2D6-specific CD8 T cells via tetramer staining.

218 y, IFN-gamma production, and cytotoxicity of CYP2D6-specific CD8 T cells were higher at diagnosis tha

219 T-regs generated under CYP2D6-specific conditions and cocultured with smDCs are

220 Conclusion: T-regs generated under CYP2D6-specific conditions and cocultured with smDCs are

221 CYP2D6-specific protein expression was detected in the l

222 CYP2D6-specific regulatory T cells (CYP2D6 T-regs) were

223 CYP2D6-specific regulatory T cells (CYP2D6 T-regs) were

224 moxifen metabolism and the evidence relating CYP2D6 status to breast cancer outcomes in tamoxifen-tre

225 le studies have examined the relationship of CYP2D6 status to breast cancer outcomes in tamoxifen-tre

226 or preclinical pharmacological evaluation of CYP2D6 substrates because of marked species differences

227 inical evidence indicates that metabolism of CYP2D6 substrates is increased during pregnancy, but the

228 a gene modulates in vivo pharmacokinetics of CYP2D6 substrates, a mouse line carrying both the CYP2D6

229 ficant individual differences in response to CYP2D6 substrates.

230 P2C19, and CYP17A1 but not that of CYP2E1 or CYP2D6, suggesting that the b(5) interaction varies amon

231 hondrion-targeted human cytochrome P450 2D6 (CYP2D6), supported by mitochondrial adrenodoxin and adre

232 quence were critical to the synergistic smDC-CYP2D6 T-reg immunoregulatory functions, and lack of eit

233 quence were critical to the synergistic smDC-CYP2D6 T-reg immunoregulatory functions, and lack of eit

234 semimature dendritic cells (smDCs), and smDC-CYP2D6 T-regs also expressed high levels of FOXP3 (forkh

235 semimature dendritic cells (smDCs), and smDC-CYP2D6 T-regs also expressed high levels of FOXP3 (forkh

236 CYP2D6-specific regulatory T cells (CYP2D6 T-regs) were obtained from peptide-pulsed monocyt

237 CYP2D6-specific regulatory T cells (CYP2D6 T-regs) were obtained from peptide-pulsed monocyt

238 ificantly boosted the suppressive ability of CYP2D6 T-regs.

239 ificantly boosted the suppressive ability of CYP2D6 T-regs.

240 ell immune responses to cytochrome P450IID6 (CYP2D6), the autoantigen of autoimmune hepatitis type 2

241 ell immune responses to cytochrome P450IID6 (CYP2D6), the autoantigen of autoimmune hepatitis type 2

242 orphic dinucleotide repeat markers linked to CYP2D6 to determine whether the association was present

243 ts demonstrate a significant contribution by CYP2D6 to the catalysis of tam-4-hydroxylation by human

244 aplotypes for investigating the evolution of CYP2D6 variation.

245 on results that Hosking et al. obtained near CYP2D6 were almost identical before and after marker sel

246 of 10 dinucleotide repeat markers linked to CYP2D6 were associated with the disease.

247 ressing predominantly mitochondrion-targeted CYP2D6 were more sensitive to MPTP-mediated mitochondria

248 mes (cytochrome P450 3A4 and 2D6 [CYP3A4 and CYP2D6]) were also measured in these 17 patients.

249 Moreover, docking into the CYP2D6 X-ray structure provided a reliable alignment for