ライフサイエンスコーパス: leflunomide

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

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

3 ients with rheumatoid arthritis treated with leflunomide.

4 disrupted with increasing concentrations of leflunomide.

5 brogated by treatment of Jurkat T cells with leflunomide.

6 the in vivo immunosuppressive activities of leflunomide.

7 educing agents did not reverse the effect of leflunomide.

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

9 e reversed the antiproliferative activity of leflunomide.

10 The active metabolite of leflunomide.

11 pendent antigen responses were suppressed by leflunomide.

12 eritis have responded to the immunomodulator leflunomide.

13 were switched from mycophenolate mofetil to leflunomide.

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

15 and treated with varying doses of FK778 and leflunomide.

16 kg to cohorts or animals receiving FK778 and leflunomide.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

46 Leflunomide, alone or in combination, has potential util

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

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

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

50 Leflunomide also inhibited TNF-induced activation of AP-

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

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

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

54 Leflunomide, an inhibitor of protein kinase activity and

55 Leflunomide, an inhibitor of protein kinase activity and

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

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

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

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

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

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

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

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

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

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

66 The combination of leflunomide and cyclosporine controlled myocutaneous all

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

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

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

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

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

72 Leflunomide and its active metabolite teriflunomide inhi

73 Leflunomide and its active metabolite, A771726, are stru

74 Combination therapy with leflunomide and methotrexate provides statistically sign

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

76 ificant pharmacokinetic interactions between leflunomide and methotrexate were noted.

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

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

79 ndicated reduction of inflammation with both leflunomide and methotrexate.

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

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

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

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

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

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

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

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

88 108 pregnant women with RA not treated with leflunomide, and 78 healthy pregnant women were enrolled

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

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

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

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

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

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

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

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

97 Methotrexate and leflunomide are teratogenic and should be avoided during

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

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

100 Leflunomide blocked the degradation of I kappa B alpha a

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

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

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

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

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

106 Leflunomide combined with cyclosporine prevented whole l

107 Leflunomide diminished the tyrosine phosphorylation of J

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

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

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

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

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

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

114 Leflunomide exerts these effects by inhibiting the trans

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

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

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

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

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

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

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

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

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

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

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

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

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

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

129 15-deoxyspergulin, mycophenolate mofetil, or leflunomide from day 0, 7, or 14 until day of graft remo

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

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

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

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

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

135 = 179 +/- 19 nM), while the parent compound, leflunomide, had no inhibitory effect at concentrations

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

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

138 625 copies/mL, and patients were switched to leflunomide if BK viral load did not decrease after 2 mo

139 eating BK viremia using fluoroquinolones and leflunomide in PRTR.

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

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

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

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

144 Leflunomide inhibited IgG1 secretion in this model in a

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

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

147 Leflunomide inhibits Polyoma virus replication in vitro

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

149 100 microM), and support the hypothesis that leflunomide inhibits pyrimidine synthesis in T cells.

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

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

152 Leflunomide is a novel immunosuppressive and antiinflamm

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

154 Leflunomide is a potential therapeutic option for posttr

155 Leflunomide is a pyrimidine biosynthesis inhibitor that

156 Leflunomide is an experimental drug with demonstrated ab

157 Leflunomide is an immune suppressive drug with anti vira

158 Leflunomide is an immunosuppressive drug capable of inhi

159 Leflunomide is an immunosuppressive drug capable of inhi

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

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

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

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

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

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

166 Leflunomide (Lef) is a novel immunosuppressant that can

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

188 Leflunomide or matching placebo added to existing methot

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

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

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

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

193 Leflunomide plus methotrexate is generally well tolerate

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

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

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

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

198 Leflunomide, rapamycin, and cyclosporine effectively pre

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

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

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

202 Leflunomide seems to possess substantial immune suppress

203 Methotrexate and leflunomide should not be used.

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

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

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

207 Leflunomide suppressed TNF-induced phosphorylation of I-

208 Leflunomide suppressed TNF-induced reactive oxygen inter

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

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

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

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

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

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

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

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

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

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

219 Leflunomide treatment was associated with a significantl

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

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

222 0.001), and treatment with ciprofloxacin and leflunomide was associated with improved eGFR (P<0.001).

223 Leflunomide was dosed to a targeted blood level of activ

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

225 Leflunomide was initiated after a median of three episod

226 adverse events requiring discontinuation of leflunomide were encountered.

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

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

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

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

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

232 Leflunomide, which prevents acute xenograft rejection, p

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