ライフサイエンスコーパス: atovaquone

1 ty of the bovine bc1 complex (Ki = 80 nm) to atovaquone.

2 erential sensitivity of these two species to atovaquone.

3 e bc(1) complexes resistant to inhibition by atovaquone.

4 or this study we focus on the anti-malarial, atovaquone.

5 new antimalarial agents: 5-fluoroorotate and atovaquone.

6 line and a broad spectrum antiparasitic drug atovaquone.

7 an endochin-like quinolone (ELQ) prodrug and atovaquone.

8 fected patients receiving treatment doses of atovaquone.

9 to established antimalarials chloroquine and atovaquone.

10 ng clinical isolates harboring resistance to atovaquone.

11 cross-resistance with the antimalarial drug atovaquone.

12 that are resistant to the anti-malarial drug atovaquone.

13 intaining little to no cross-resistance with atovaquone.

14 sensitivity of the cytochrome bc1 complex to atovaquone.

15 ve either enhanced or reduced sensitivity to atovaquone.

16 developed in 122 of 536 patients assigned to atovaquone (15.7 cases per 100 person-years), as compare

17 mg twice daily (BID) for 14 days followed by atovaquone 1500 mg BID for 14 days, or vice-versa, with

18 open-label, randomized trial comparing daily atovaquone (1500-mg suspension) with daily dapsone (100

19 0 subjects receiving EFV in combination with atovaquone 750 mg BID achieved an atovaquone C avg>18.5

20 ggest that the currently recommended dose of atovaquone 750 mg BID for treatment of mild to moderate

21 of 10 subjects receiving EFV-based cART plus atovaquone 750 mg BID had an atovaquone C avg>15 microg/

22 Subjects were randomly assigned to atovaquone 750 mg twice daily (BID) for 14 days followed

23 The subjects were assigned to receive either atovaquone (750 mg every 12 hours) and azithromycin (500

24 Atovaquone, a 2-hydroxynaphthoquinone, is a competitive

25 roximately 200 fold) than that observed with atovaquone, a licensed bc(1)-specific antimalarial drug.

26 t parasites with different concentrations of atovaquone, a mitochondrial inhibitor, the recovery of d

27 Resistance to atovaquone, a second-line agent, may also be developing.

28 Atovaquone, a ubiquinone analogue, targets C. felis cyto

29 etermine the pharmacokinetics of aerosolized atovaquone (administered with and without a synthetic su

30 llowing dose regimens: (1) 250 milligrams of atovaquone and 100 milligrams of proguanil (250/100 mill

31 milligrams on day -7, (4) 500 milligrams of atovaquone and 200 milligrams of proguanil (500/200 mill

32 igrams) on day -7 or, (5) 1000 milligrams of atovaquone and 400 milligrams of proguanil (1000/400 mil

33 with this protocol, such as the antimalarial Atovaquone and antitheilerial Parvaquone, thus evidencin

34 Treatment combining atovaquone and azithromycin (A&A) has been associated wi

35 that infects domestic cats, is treated with atovaquone and azithromycin (A&A).

36 therapy in 65 percent of those who received atovaquone and azithromycin and 73 percent of those who

37 or the treatment of babesiosis, a regimen of atovaquone and azithromycin is as effective as a regimen

38 We describe the emergence of atovaquone and azithromycin resistance associated with m

39 The most common adverse effects with atovaquone and azithromycin were diarrhea and rash (each

40 d by 15 percent of the subjects who received atovaquone and azithromycin, as compared with 72 percent

41 In vitro response to atovaquone and cytochrome b sequence of clinical isolate

42 nnot tolerate trimethoprim-sulfamethoxazole, atovaquone and dapsone are similarly effective for the p

43 ith chloroquine resistance, a combination of atovaquone and proguanil or quinine plus tetracycline or

44 These findings establish atovaquone as a novel, clinically accessible STAT3 inhib

45 Six cases were receiving atovaquone as a prophylaxis.

46 ation because of adverse events was 3.78 for atovaquone as compared with dapsone (95 percent confiden

47 potency equal to that of orally administered atovaquone at 10 mg/kg.

48 l antimalarial agents acquired resistance to atovaquone at high frequency, but not to 5-fluoroorotate

49 The antitoxoplasmosis drug atovaquone, at a very low concentration (0.03 microM), t

50 Impressively, a combination of ELQ-334 and atovaquone, at doses as low as 5.0 mg/kg each, resulted

51 ceiving EFV-based cART had 47% and 44% lower atovaquone AUCtau than subjects not receiving cART at at

52 dose by aerosol, mean peak concentrations of atovaquone averaged 52 microg/mL in plasma and 31 microg

53 abesiosis consists of two drug combinations, atovaquone + azithromycin or quinine + clindamycin.

54 of the changes in cytochrome b structure and atovaquone binding with the mutated bc(1) complexes prov

55 of the amino acid side-chains may determine atovaquone-binding affinity, and thereby selective toxic

56 e, including amino acid substitutions in the atovaquone-binding regions of cytochrome b (cytb) and th

57 ovide the first molecular description of how atovaquone binds to the bc1 complex and explain the diff

58 These results indicate that atovaquone binds to the ubiquinol oxidation pocket of th

59 Here, we show that atovaquone blocks this domain movement by locking the ir

60 based cART plus atovaquone 750 mg BID had an atovaquone C avg>15 microg/mL, which has previously been

61 ation with atovaquone 750 mg BID achieved an atovaquone C avg>18.5 microg/mL, a concentration that ha

62 que metabolic signatures were also found for atovaquone, chloroquine, proguanil, cycloguanil and meth

63 We observed that only atovaquone collapsed DeltaPsim and inhibited parasite re

64 ge for future clinical evaluation of ELQ and atovaquone combination therapy for treatment of human ba

65 in 33% of isolates from patients exposed to atovaquone, compared with 6% from those who were not (P=

66 ructural basis for the selective toxicity of atovaquone could help in designing drugs against infecti

67 azole, with second-line therapies, including atovaquone, dapsone, and pentamide.

68 me b, the sensitivity of the yeast enzyme to atovaquone decreased (Ki = 100 nm) with no loss in activ

69 e AUCtau than subjects not receiving cART at atovaquone doses of 750 mg BID and 1500 mg BID, respecti

70 In addition, atovaquone eradicates hypoxia in FaDu, HCT116 and H1299

71 Atovaquone exposure (area under the curve) during liver

72 re common in patients with AIDS and PCP with atovaquone exposure, but the clinical significance of th

73 posure were matched with 45 patients with no atovaquone exposure.

74 carinii pneumonia (PCP) are associated with atovaquone exposure.

75 ng on the reduction of cross-resistance with atovaquone for activity against the clinical isolates W2

76 c stem cell transplantation, extended use of atovaquone for Pneumocystis prophylaxis was associated w

77 Furthermore, atovaquone had no effect on mammalian DeltaPsim.

78 the field, greatly enhancing the utility of atovaquone in malaria control.

79 Resistance to atovaquone in the field is associated with point mutatio

80 ant) and to evaluate the efficacy of inhaled atovaquone in the prevention and treatment of Pneumocyst

81 val of rats with PCP and, when combined with atovaquone, increased plasma and lung concentrations of

82 In these enzymes, the IC(50) for atovaquone increases from 25 nm for the enzyme from wild

83 In malaria parasites, atovaquone inhibits mitochondrial electron transport at

84 Atovaquone inhibits respiration in target organisms by s

85 utinely achieved clinically in human plasma, atovaquone inhibits STAT3 phosphorylation, the expressio

86 Atovaquone inhibits the bc1 complex competitively with a

87 Atovaquone is a substituted 2-hydroxynaphthoquinone that

88 Atovaquone is a substituted hydroxynaphthoquinone that i

89 Atovaquone is a substituted hydroxynaphthoquinone that i

90 Atovaquone is a ubiquinone analogue, and decreases the O

91 Atovaquone is an anti-malarial drug used in combination

92 Atovaquone is an antiparasitic drug that selectively inh

93 However, among those not receiving dapsone, atovaquone is better tolerated and may be the preferred

94 t a 7- to 10-day course of azithromycin plus atovaquone is effective for mild babesiosis.

95 Atovaquone is not a kinase inhibitor but instead rapidly

96 to a commonly used antimalarial medication, atovaquone, is apparently unable to spread.

97 A computed energy-minimized structure for atovaquone liganded to the yeast bc1 complex suggests th

98 oelii; these mutants exhibited resistance to atovaquone-mediated collapse of mitochondrial membrane p

99 expression signature of STAT3, we discovered atovaquone (Mepron), an antimicrobial approved by the US

100 Atovaquone (Mepron, 566c80) is an effective agent agains

101 lysis of recrudescent parasites after ELQ or atovaquone monotherapy identified genetic substitutions

102 roviral therapy (cART) impacted steady-state atovaquone plasma concentrations in human immunodeficien

103 A promising alternative treatment is atovaquone plus azithromycin.

104 Atovaquone pressure selects parasites with mutations in

105 artesunate-amodiaquine (2.9%) and artesunate-atovaquone-proguanil (1.0%) groups.

106 An additional group received daily atovaquone-proguanil (250-100 mg) for 9 days, starting 1

107 (cohort 1A), six participants received daily atovaquone-proguanil 1 day before CHMI (cohort 1B), and

108 oral regimen only (95 AL, 162 mefloquine, 36 atovaquone-proguanil [AP], and 17 others), and 87 were a

109 M265 1 day before CHMI and six of six in the atovaquone-proguanil cohort were protected, whereas plac

110 Indonesia or Papua New Guinea, in which case atovaquone-proguanil is best, with mefloquine or quinine

111 Single-dose atovaquone-proguanil provides effective malaria chemopro

112 re observed after artesunate-amodiaquine and atovaquone-proguanil therapies, respectively.

113 ble-blind trial to establish the efficacy of atovaquone-proguanil to prevent malaria with the goal of

114 iaquine, atovaquone-proguanil, or artesunate-atovaquone-proguanil treatment groups and followed for 2

115 Artesunate-atovaquone-proguanil was a highly effective alternative

116 Atovaquone-proguanil was characterized by a slow blood s

117 Artesunate-atovaquone-proguanil was not associated with any failure

118 istance, few alternative non-ACTs, including atovaquone-proguanil, are currently available.

119 randomly assigned to artesunate-amodiaquine, atovaquone-proguanil, or artesunate-atovaquone-proguanil

120 Allocation to DSM265, atovaquone-proguanil, or placebo was randomised by an in

121 However, the proportion of atovaquone-proguanil-treated patients with positive smea

122 also resistant to the synergistic effects of atovaquone/ proguanil combination.

123 Atovaquone/proguanil was the most commonly prescribed an

124 ochrome b genes from 2 of 4 patients who had atovaquone prophylaxis failure contained mutations resul

125 Fifteen patients with previous atovaquone prophylaxis or treatment exposure were matche

126 nce of PCP was significantly associated with atovaquone prophylaxis.

127 Atovaquone rapidly decreases the OCR by more than 80% in

128 dertaking clinical studies to assess whether atovaquone reduces tumour hypoxia in patients, thereby i

129 Atovaquone represents a class of antimicrobial agents wi

130 f this class to overcome parasite Q(o)-based atovaquone resistance and provides critical structural i

131 Based on our malaria atovaquone resistance data, a series of cytochrome b mut

132 To assess the possibility that atovaquone resistance might be developing, the genes for

133 To better understand the molecular basis of atovaquone resistance, we have introduced seven of the m

134 ative explanation for the molecular basis of atovaquone resistance.

135 e and cytochrome b sequence did not indicate atovaquone resistance.

136 viding direct proof that the mutation causes atovaquone resistance.

137 cular and biochemical characterization of an atovaquone-resistant field isolate, TM902CB.

138 To that end, we derived nine independent atovaquone-resistant malaria parasite lines by suboptima

139 have introduced seven of the mutations from atovaquone-resistant P. jirovecii into the cytochrome b

140 levels of expression, compared with the 3D7 (atovaquone-sensitive) control strain in bc(1) and cytoch

141 This suggests that atovaquone, shown to inhibit mitochondrial electron tran

142 Atovaquone targets parasite cytochrome b.

143 parasites rendered the complex resistant to atovaquone, thereby providing direct proof that the muta

144 The administration of oral atovaquone to mice inhibited tumor growth and prolonged

145 The recent, growing failure of atovaquone treatment and increased mortality of patients

146 The failure of atovaquone treatment and mortality of patients with mala

147 These effects were also observed with atovaquone treatment of primary blasts isolated from pat

148 se of reactive oxygen species resulting from atovaquone treatment.

149 ases per 100 person-years; relative risk for atovaquone vs. dapsone, 0.85; 95 percent confidence inte

150 When atovaquone was combined with surfactant, mean peak conce

151 Atovaquone was shown to inhibit the respiratory chain of

152 50% growth inhibition, while the IC(50) for atovaquone (which does not inhibit FPPS) remained the sa

153 shift of the inhibitory constant (K(i)) for atovaquone with a concomitant reduction in the V(max) of

154 ogates to model the molecular interaction of atovaquone with human and resistant pathogen enzymes.

155 We have examined the interaction of atovaquone with the bc1 complex isolated from Saccharomy