ライフサイエンスコーパス: leflunomide

1 matic drugs (DMARDs) (either methotrexate or leflunomide).

2 ture and DDX21 occupancy changes prompted by leflunomide.

3 ations of A77 1726, the active metabolite of leflunomide.

4 ients with rheumatoid arthritis treated with leflunomide.

5 disrupted with increasing concentrations of leflunomide.

6 brogated by treatment of Jurkat T cells with leflunomide.

7 the in vivo immunosuppressive activities of leflunomide.

8 educing agents did not reverse the effect of leflunomide.

9 s an Src protein tyrosine kinase, p56lck, by leflunomide.

10 ved in the Z form during the ring opening of leflunomide.

11 e reversed the antiproliferative activity of leflunomide.

12 The active metabolite of leflunomide.

13 pendent antigen responses were suppressed by leflunomide.

14 eritis have responded to the immunomodulator leflunomide.

15 were switched from mycophenolate mofetil to leflunomide.

16 and treated with varying doses of FK778 and leflunomide.

17 kg to cohorts or animals receiving FK778 and leflunomide.

18 Allograft recipients (n=6) administered leflunomide (10 mg/kg/24 hr) rejected their allografts i

19 oup of allograft recipients was treated with leflunomide (10 mg/kg/24 hr/orally) and cyclosporine (5

20 (mean +/- SD) for > or =6 months were given leflunomide, 10-20 mg/day.

21 the immunosuppressive activities of low-dose leflunomide (15 mg/kg/day) and partially antagonized the

22 Our data demonstrate that the ability of leflunomide (25-100 microM) to inhibit MLC and CTLL-4 ce

23 Toxicities associated with high-dose leflunomide (35 mg/kg/day) were anemia, diarrhea, and pa

24 he immunosuppressive activities of high-dose leflunomide (35 mg/kg/day).

25 k2 levels were decreased, in the presence of leflunomide, 48 hr after stimulation.

26 lanted with hamster hearts were treated with leflunomide (5 mg/kg/day by gavage) for 14-21 days and C

27 of leflunomide, after a single treatment of leflunomide (5, 15, and 35 mg/kg).

28 agonized the immunosuppressive activities of leflunomide (5, 15, and 35 mg/kg/day) in the allotranspl

29 r hearts were treated for 50 or 75 days with leflunomide (5, 15, and 35 mg/kg/day; gavage) alone or i

30 ins Clinical Compound Library and identified leflunomide, a dihydroorotate dehydrogenase inhibitor wi

31 We show that the active metabolite of leflunomide, a drug approved for treatment of arthritis,

32 Leflunomide, a drug for rheumatoid arthritis, has been r

33 A77 1726 (LEF) is the active metabolite of leflunomide, a recently approved immunosuppressive agent

34 vities reported for the active metabolite of leflunomide, A77 1726, are inhibition of tyrosine phosph

35 Brequinar and the active metabolite of leflunomide, A77 1726, have been clearly shown to inhibi

36 The immunosuppressive metabolite of leflunomide, A77 1726, inhibits the enzymatic activity o

37 fied for the immunosuppressive metabolite of leflunomide, A77 1726: inhibition of dihydroorotate dehy

38 Leflunomide abrogates the effective transcription elonga

39 This indicated that leflunomide acted as a pyrimidine synthesis inhibitor, t

40 These studies revealed that leflunomide acted comparably to rapamycin, but was disti

41 Taken together, these data suggest that leflunomide acts as a tyrosine kinase inhibitor to block

42 he p65 subunit of NF-kappaB, suggesting that leflunomide acts downstream of NIK.

43 concentrations in Lewis rats and the dose of leflunomide administered.

44 levels of A77 1726, the active metabolite of leflunomide, after a single treatment of leflunomide (5,

45 monstrated equivalent inhibitory activity of leflunomide against multi-drug-resistant CMV isolates.

46 ssible mechanisms for inhibitory activity of leflunomide against rheumatoid arthritis.

47 roven NK virus nephropathy (BKN) with either leflunomide alone (n=17) or leflunomide plus a course of

48 Leflunomide, alone or in combination, has potential util

49 We in this study show that leflunomide also blocks NF-kappaB reporter gene expressi

50 Leflunomide also increased the risk (HR 1.2 [95% confide

51 estricted to TNF-induced activation, because leflunomide also inhibited NF-kappa B activation induced

52 Leflunomide also inhibited TNF-induced activation of AP-

53 Leflunomide also suppressed the TNF-activated NF-kappa B

54 Data generated by these studies distinguish leflunomide among immunosuppressants as uniquely capable

55 These findings imply that leflunomide, an effective immunosuppressive agent, shows

56 Leflunomide, an inhibitor of protein kinase activity and

57 Leflunomide, an inhibitor of protein kinase activity and

58 phenyl)-7(t-butyl)pyrazol(3,4-d)pyramide and leflunomide, an Src kinase inhibitor, suppressed both UV

59 The leflunomide analog, FK778, is a selective pyrimidine syn

60 Thirty-four patients (17 treated with leflunomide and 17 with methotrexate) had usable baselin

61 e basis, we have investigated the effects of leflunomide and A771726 on the activity of purified reco

62 ate inhibition of MLC by the combinations of leflunomide and brequinar sodium or mycophenolic acid.

63 at a brief treatment with the combination of leflunomide and CsA profoundly modifies the humoral xeno

64 A 7-day treatment with leflunomide and CsA was able to convert xenoreactivity f

65 ceiving hamster hearts by the combination of leflunomide and CsA.

66 The combination of two immunosuppressants, leflunomide and cyclosporin A (CsA), completely inhibits

67 ecipients were administered a combination of leflunomide and cyclosporine (10 mg/kg/24 hr and 5 mg/kg

68 The combination of leflunomide and cyclosporine controlled myocutaneous all

69 The immunosuppressive effects of leflunomide and cyclosporine were evaluated in a rat neu

70 igated the effect of two immunosuppressants, leflunomide and cyclosporine, on the spleen of rats with

71 ed inhibitory effects on other viruses, both leflunomide and FK778 can augment HBV replication.

72 Here, we show that leflunomide and FK778 strongly enhance hepatitis B virus

73 The inhibitors of pyrimidine synthesis, leflunomide and FK778, have been reported to exert broad

74 Leflunomide and its active metabolite teriflunomide inhi

75 Leflunomide and its active metabolite, A771726, are stru

76 Combination therapy with leflunomide and methotrexate provides statistically sign

77 milar capacity to detect greater efficacy of leflunomide and methotrexate versus placebo in this clin

78 ificant pharmacokinetic interactions between leflunomide and methotrexate were noted.

79 rse effects, pharmacokinetic measurements of leflunomide and methotrexate, and clinical response by A

80 andomized, active-controlled trial comparing leflunomide and methotrexate.

81 ndicated reduction of inflammation with both leflunomide and methotrexate.

82 In the leflunomide and placebo groups, 46.2% and 19.5% of patie

83 Differences between leflunomide and placebo were 30-36%, and differences bet

84 important differences between methotrexate, leflunomide and sulfasalazine monotherapies; early disea

85 Of these drugs, leflunomide and teriflunomide could suppress SOCE signif

86 rheumatoid arthritis or multiple sclerosis (leflunomide and teriflunomide) and have been investigate

87 o inadvertently become pregnant while taking leflunomide and undergo the washout procedure.

88 ate pregnancy outcomes in women who received leflunomide and were treated with cholestyramine during

89 limus (rapamycin), mycophenolate mofetil and leflunomide (and its malononitriloamide analogs).

90 108 pregnant women with RA not treated with leflunomide, and 78 healthy pregnant women were enrolled

91 y a combination of immunosuppressive agents, leflunomide, and cyclosporine.

92 esented showing that dehydroepiandrosterone, leflunomide, and methotrexate are effective in treating

93 bolites, such as methotrexate, azathioprine, leflunomide, and mycophenolate, are often used as altern

94 g synthetic DMARDs (limited to methotrexate, leflunomide, and sulfasalazine) or among anti-tumor necr

95 Leflunomide (Arava), a drug widely used for treatment of

96 ive concentration, and selectivity index for Leflunomide are 39.7+/-6.9, 11.3+/-2.8, and 3.8+/-0.8 mi

97 Women treated with leflunomide are advised to avoid pregnancy; those who be

98 sed in a stepwise fashion, ciprofloxacin and leflunomide are effective and safe treatments for BK vir

99 Methotrexate and leflunomide are teratogenic and should be avoided during

100 Cidofovir and Leflunomide are used empirically in the treatment of BK

101 In a drug screen, we identified leflunomide as an agent that reduces apoptosis and activ

102 as an adverse event in patients treated with leflunomide between November 1998 and January 2000.

103 Leflunomide blocked the degradation of I kappa B alpha a

104 ammatory stimuli, including TNF, but whether leflunomide blocks NF-kappa B activation is not known.

105 heumatoid arthritis led us to postulate that leflunomide blocks TNF signaling.

106 eatment of a human T cell line (Jurkat) with leflunomide blocks TNF-mediated NF-kappa B activation in

107 ity, more recent studies have suggested that leflunomide can also inhibit pyrimidine synthesis.

108 previous biochemical studies indicated that leflunomide can inhibit src-family tyrosine kinase activ

109 2 with 5-fluorouracil or the DHODH inhibitor leflunomide caused regressions of multiple colorectal xe

110 Current studies do not support the usage of leflunomide, cidofovir, quinolones, or IVIGs.

111 Leflunomide combined with cyclosporine prevented whole l

112 Leflunomide diminished the tyrosine phosphorylation of J

113 umatoid arthritis (RA) who were treated with leflunomide during pregnancy (95.3% of whom received cho

114 d new disease-modifying antirheumatic drugs (leflunomide, etanercept, and infliximab) in their choice

115 rheumatic drugs (DMARDs) have been approved: leflunomide, etanercept, and infliximab.

116 osporine, hydroxychloroquine, sulfasalazine, leflunomide, etanercept, and infliximab.

117 These findings, in demonstrating that leflunomide exerts antiviral activity against HSV-1 by m

118 ntrast to currently approved anti-CMV drugs, leflunomide exerts no inhibitory effect on the accumulat

119 Leflunomide exerts these effects by inhibiting the trans

120 Infants in both the leflunomide-exposed and non-leflunomide-exposed RA group

121 were no significant differences between the leflunomide-exposed and non-leflunomide-exposed RA group

122 ants in both the leflunomide-exposed and non-leflunomide-exposed RA groups were born smaller and earl

123 nces between the leflunomide-exposed and non-leflunomide-exposed RA groups.

124 ed risk of adverse pregnancy outcomes due to leflunomide exposure among women who undergo cholestyram

125 Two studies of inadvertent leflunomide exposure during early pregnancy suggest that

126 e form of tacrolimus (MR-4), a new analog of leflunomide (FK 778), and several novel compounds (PG 49

127 ently counteracted the stimulatory effect of leflunomide, FK778, and MPA on HBV replication.

128 le for the enhancement of HBV replication by leflunomide, FK778, and MPA.

129 Treatment with leflunomide, FK778, or MPA may bear the risk to enhance

130 d including the adjunctive use of cidofovir, leflunomide, fluoroquinolones, and intravenous immunoglo

131 U.S. Food and Drug Administration, including leflunomide, flutamide, and nimodipine.

132 ) and treated with varying doses of FK778 or leflunomide for 28 days.

133 Fifty-three patients received leflunomide from 5 days to more than 430 days, and 37 pa

134 15-deoxyspergulin, mycophenolate mofetil, or leflunomide from day 0, 7, or 14 until day of graft remo

135 iscriminate further the action on T cells of leflunomide from other immunosuppressive agents, we perf

136 dition of exogenous uridine, suggesting that leflunomide functions as a pyrimidine synthesis inhibito

137 A number of studies demonstrate that leflunomide functions both as a pyrimidine synthesis inh

138 In this study we demonstrate that leflunomide functions to inhibit murine B cell antibody

139 milar in both treatment groups (23.1% in the leflunomide group and 24.8% in the placebo group), as we

140 = 179 +/- 19 nM), while the parent compound, leflunomide, had no inhibitory effect at concentrations

141 The combination of methotrexate and leflunomide has therapeutic potential in RA.

142 itionally described an FDA approved prodrug, leflunomide (IC(50), 6.8 microM), that seems to be a PXR

143 625 copies/mL, and patients were switched to leflunomide if BK viral load did not decrease after 2 mo

144 of dihydroorotate dehydrogenase (DHODH) with leflunomide impacts nucleotide pools by reducing pyrimid

145 eating BK viremia using fluoroquinolones and leflunomide in PRTR.

146 We investigated the effects of leflunomide in vivo and report that amelioration of lymp

147 ested that the immunosuppressive efficacy of leflunomide in vivo is related to inhibition of DHO-DHas

148 Exposure of patient-derived colonoids to leflunomide increased cell survival, polarity, and trans

149 tosis (XIAP); incubation of these cells with leflunomide increased levels of phosphorylated AKT and X

150 1, and the immunosuppressive small-molecule leflunomide, induced intestinal immunotolerance and redu

151 ddx21-deficient zebrafish show resistance to leflunomide-induced stress.

152 itial in vitro experiments demonstrated that leflunomide inhibited B cell antibody production by decr

153 These data further confirmed that leflunomide inhibited B cell progression through the S p

154 Leflunomide inhibited IgG1 secretion in this model in a

155 Leflunomide inhibited virus replication in the lungs of

156 We hypothesized that leflunomide inhibits LPS-induced IgG secretion by inhibi

157 We previously reported that leflunomide inhibits LPS-stimulated B cell proliferation

158 Leflunomide inhibits Polyoma virus replication in vitro

159 hat the experimental immunosuppressive agent leflunomide inhibits production of cytomegalovirus by in

160 100 microM), and support the hypothesis that leflunomide inhibits pyrimidine synthesis in T cells.

161 Previously, we have demonstrated that leflunomide inhibits TNF-induced NF-kappaB activation by

162 gest that A77 1726, the active metabolite of leflunomide, inhibits the activity of JAK1 and JAK3.

163 sformation of antirheumatic fluorescent drug leflunomide into its active metabolite teriflunomide thr

164 Leflunomide is a novel immunosuppressive and antiinflamm

165 Our results thus indicate that leflunomide is a potent inhibitor of NF-kappa B activati

166 Leflunomide is a potential therapeutic option for posttr

167 Leflunomide is a pyrimidine biosynthesis inhibitor that

168 Leflunomide is an anti-inflammatory drug primarily used

169 Leflunomide is an experimental drug with demonstrated ab

170 Leflunomide is an immune suppressive drug with anti vira

171 Leflunomide is an immunosuppressive drug capable of inhi

172 Leflunomide is an immunosuppressive drug capable of inhi

173 enzymatic assays, however, demonstrate that leflunomide is an inhibitor of several protein tyrosine

174 he in vivo mechanism of immunosuppression by leflunomide is complex and is affected by at least the f

175 The in vitro activity of Cidofovir and Leflunomide is modest, and the selectivity index is low.

176 iseases in MRL/MpJ-lpr/lpr (lpr/lpr) mice by leflunomide is not accompanied by reduced PyN concentrat

177 roorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neu

178 hamster hearts into Lewis rats treated with leflunomide (Lef) continuously at 15 mg/kg/day.

179 Leflunomide (Lef) is a novel immunosuppressant that can

180 safety data comparing methotrexate (MTX) and leflunomide (LEF) monotherapy, in combination with biolo

181 effects of the immunosuppressants FK506 and leflunomide (Lef) on the survival of hamster hearts and

182 this study was to investigate the effect of Leflunomide (Lef), alone or in combination with a subopt

183 orted previously that the immunosuppressant, leflunomide (Lef), can prevent allogeneic and xenogeneic

184 o novel agents, 15-deoxyspergualin (DSG) and leflunomide (LEF), with reported anti-B-cell and/or anti

185 nd, randomized, controlled trials have shown leflunomide (LEF; 20 mg/day, loading dose 100 mg x 3 day

186 The novel leflunomide (LFM) analog, HMR 279, potentiates the immun

187 ated with cyclosporine (CsA, 10 mg/kg p.o.), leflunomide (LFM, 20 mg/kg p.o.), or rapamycin (RPM, 6 m

188 ty in vivo lends support to the promise that leflunomide may be effective for clinical islet transpla

189 olony formation demonstrated dose-dependent, leflunomide-mediated inhibition of EC proliferation.

190 eceptor (Pgr) signalling strongly suppressed leflunomide-mediated neural crest effects in zebrafish.

191 res were employed for the rational design of leflunomide metabolite (LFM) analogs with a high likelih

192 FK778 is a new derivative of the active leflunomide metabolite A77 1726.

193 anti-Fas-resistant NALM-6-UM1 cells with the leflunomide metabolite analog alpha-cyano-beta-methyl-be

194 Data from a clinical trial of leflunomide, methotrexate, and placebo treatment over 1

195 disease processes led us to hypothesize that leflunomide might act directly upon the endothelial cell

196 The isoxazole ring opening in a leflunomide molecule was modeled at the B3LYP-D3/6-311++

197 This review focuses on those drugs (leflunomide, mycophenolate mofetil, sirolimus, tacrolimu

198 ouble-blind clinical trial to receive either leflunomide (n = 18) or methotrexate (n = 21) therapy fo

199 t analysis and immunohistochemical staining, leflunomide neither interferes with transcription of imm

200 The suppressive effects of leflunomide on TNF signaling were completely reversible

201 Some mice were pretreated with leflunomide or 6-mercaptopurine.

202 e IgG1 promoter decreased in the presence of leflunomide or leflunomide plus uridine.

203 Leflunomide or matching placebo added to existing methot

204 d in patients treated with ciprofloxacin and leflunomide (P<0.001) with only a small reduction in imm

205 ng the different methods, in patients taking leflunomide, placebo, and methotrexate, respectively, we

206 BKN) with either leflunomide alone (n=17) or leflunomide plus a course of cidofovir (n=9) and followe

207 Immunosuppression with the combination of leflunomide plus CsA completely prevents xenograft rejec

208 Leflunomide plus methotrexate is generally well tolerate

209 decreased in the presence of leflunomide or leflunomide plus uridine.

210 suggest that the primary mechanism by which leflunomide prevents autoimmune and lymphoproliferative

211 ended our previous work and demonstrate that leflunomide prevents T cell progression induced by phyto

212 Previous in vitro studies have revealed that leflunomide primarily inhibits interleukin-2-stimulated

213 Leflunomide, rapamycin, and cyclosporine effectively pre

214 microM) for the 5, 15, and 35 mg/kg doses of leflunomide, respectively.

215 In zebrafish with disruption of ttc7a, leflunomide restores gut motility, reduces intestinal tr

216 ies with LPS activated B cells revealed that leflunomide retained its inhibitory activity when added

217 However, the mechanism of leflunomide's antiarthritis activity and is not fully un

218 Leflunomide seems to possess substantial immune suppress

219 Methotrexate and leflunomide should not be used.

220 During metabolic reaction, absorption of leflunomide split into two bands resembling absorption s

221 he pyrimidine biosynthetic enzyme DHODH with leflunomide substantially impaired CRC liver metastatic

222 Switching from mycophenolate mofetil to leflunomide successfully cleared verrucae vulgares and m

223 dies, FTY720 (or tacrolimus), everolimus and leflunomide suppressed indirect activation of T cells, e

224 Leflunomide suppressed TNF-induced phosphorylation of I-

225 Leflunomide suppressed TNF-induced reactive oxygen inter

226 e of LPS-stimulated B cells we observed that leflunomide targets two different stages in cell cycle t

227 easured by IRE was significantly better with leflunomide than with methotrexate over 4 months of ther

228 Five of 70 patients who had begun leflunomide therapy had significant weight loss that cou

229 The duration of leflunomide therapy ranged from 1 to 24 months (median 3

230 l load and higher viral load at the start of leflunomide therapy were associated with failure to supp

231 s replication in vitro and closely monitored leflunomide therapy with specifically targeted blood lev

232 uorescence spectra reveal slow conversion of leflunomide to E and Z forms of teriflunomide in aqueous

233 ive metabolite of the anti-inflammatory drug leflunomide to the target cavities of the P. falciparum

234 The patient was taking prednisone and leflunomide to treat rheumatoid arthritis.

235 Administration of leflunomide to ttc7a(-/-) zebrafish increased gut motili

236 ater environment conditions, confirming easy leflunomide-to-teriflunomide interconversion.

237 duction of multiple clinical CMV isolates in leflunomide-treated human fibroblasts and endothelial ce

238 restored proliferation and IgM secretion to leflunomide-treated LPS-stimulated B cells, as determine

239 Leflunomide treatment was associated with a significantl

240 screen for restoration of neural crest after leflunomide treatment.

241 ntified drugs that increased cell viability; leflunomide (used to treat patients with inflammatory co

242 ent signal cascade components suggested that leflunomide was acting on a common component required fo

243 e agents, we performed kinetic studies where leflunomide was added either after the initiation of mix

244 0.001), and treatment with ciprofloxacin and leflunomide was associated with improved eGFR (P<0.001).

245 Leflunomide was dosed to a targeted blood level of activ

246 In preclinical reproductive studies, leflunomide was found to be embryotoxic and teratogenic.

247 Leflunomide was initiated after a median of three episod

248 adverse events requiring discontinuation of leflunomide were encountered.

249 The side effects of ciprofloxacin and leflunomide were recorded in each patient.

250 er than MTX (azathioprine, cyclosporine, and leflunomide) were also associated with an increased risk

251 F] receptor) and a global immunosuppressant (leflunomide) were performed to determine their relative

252 h the de novo pyrimidine synthesis inhibitor leflunomide, which is not toxic to the mice, and which d

253 ysed metabolism of the immunomodulatory drug leflunomide, which likewise undergoes redox-mediated Kem

254 Leflunomide, which prevents acute xenograft rejection, p

255 cell proliferation with the combinations of leflunomide with cyclosporine or with rapamycin.