ライフサイエンスコーパス: potentiator

1 their role as 'delivery systems' or 'immune potentiators'.

2 X-770; Kalydeco), a clinically approved CFTR potentiator.

3 eptor subunit 1 sensitive to both classes of potentiator.

4 rection of modulation, rendering 5beta-DHP a potentiator.

5 ted by ivacaftor, a clinically approved CFTR potentiator.

6 of tricyclic sulfonamides as allosteric GlyR potentiators.

7 eening for mGluR5 agonists, antagonists, and potentiators.

8 closely related to their potencies as mGluR5 potentiators.

9 ity of multiple classes of allosteric mGluR1 potentiators.

10 ation of small-molecule insulin mimetics and potentiators.

11 collection for insulin-receptor agonists and potentiators.

12 s for the development of insulin mimetics or potentiators.

13 ecular mechanism of action for AMPA receptor potentiators.

14 siveness to glucose and several of its known potentiators.

15 sphorylation and binding of chloride channel potentiators.

16 eral roles for SMAD2/3 as cell-reprogramming potentiators.

17 acid type A receptors (GABAARs) rather than potentiators.

18 therapeutic benefits of CFTR correctors and potentiators.

19 ing-fused thiadiazine dioxides class of AMPA potentiators.

20 lifetime, and sensitivity to the allosteric potentiator 3-[3-(3-pyridinyl)-1,2,4-oxadiazol-5-yl]benz

21 s of both the allosteric antagonist MPEP and potentiators 3,3'-difluorobenzaldazine and 3-cyano-N-(1,

22 es the binding affinity of the AMPA receptor potentiator [(3)H]-LY450295 and confers sensitivity to d

23 nenolone sulfate) and the GluN2C/D-selective potentiator [(3-chlorophenyl)(6,7-dimethoxy-1-((4-methox

24 It has been suggested that two allosteric potentiators, 3,3'-difluorobenzaldazine and 3-cyano-N-(1

25 ructural optimization provided highly potent potentiator 32 (AM-3607), which was cocrystallized with

26 of compounds with independent corrector and potentiator activities (termed CoPo).

27 revealed 6 compounds with dual corrector and potentiator activities and 13 compounds with only potent

28 ar EC(50) for DeltaPhe508-CFTR corrector and potentiator activities by short-circuit current assay.

29 compounds with bona fide dual corrector and potentiator activities have not been identified.

30 Compounds with dual corrector and potentiator activities may be useful for single-drug tre

31 Maximal corrector and potentiator activities were comparable with those confer

32 acking conformations to elicit corrector and potentiator activities.

33 onformational requirements for corrector and potentiator activities.

34 tiator activities and 13 compounds with only potentiator activity.

35 lectivity versus M1 and M3, with no M2 or M4 potentiator activity.

36 The DeltaF508-CFTR potentiators also activated wild-type and G551D CFTR, al

37 unctionally linking allosteric AMPA receptor potentiator and antagonist sites.

38 ors, axon and dendrite pathfinders, a NeuroD potentiator and other neuronal activities.

39 orms two functions at the synapse: nonlinear potentiator and safety brake.

40 regulate the pharmacology of allosteric AMPA potentiators and antagonists in the cerebellum and hippo

41 In transfected cell systems, certain potentiators and correctors, including VX-809 and VX-770

42 address a different cellular CF defect from potentiators and correctors, our inhibitors provide an a

43 But consideration of these immune potentiators and delivery systems has become important t

44 in, in contrast to the uncharged, allosteric potentiators and inhibitors that also bind within the de

45 AMPA receptor potentiators and non-competitive antagonists represent p

46 d structural features of active and inactive potentiators and successfully predicting the activity of

47 are likely to complicate efforts to identify potentiators and/or correctors of the deltaF508 defect.

48 be recovered by pharmaceutical modulators ("potentiators" and "correctors"), but DeltaF508-CFTR can

49 linical trials combining ivacaftor (a gating potentiator) and lumacaftor (a folding corrector) have p

50 pies, microbiome-based therapies, antibiotic potentiators, and antisense approaches.

51 r low potencies, previously described mGluR5 potentiators are not useful for functional studies in na

52 ortant implications for development of AMPAR potentiators as therapeutic agents.

53 The divalent cation Zn(2+) is a potent potentiator at the strychnine-sensitive glycine receptor

54 a potentiator, or converted to inhibitor and potentiator based on concentration.

55 results obtained in previous series of AMPA potentiators belonging to 3,4-dihydro-2H-benzo- and 3,4-

56 Both potentiators bind within the dimer interface of the nond

57 Importantly, the potentiator binding site is adjacent to the "hinge" in t

58 nfers partial sensitivity of [(3)H]-LY450295 potentiator binding to displacement by non-competitive a

59 lyRalpha3cryst to afford the first described potentiator-bound X-ray cocrystal structure within this

60 st acetylcholine (ACh), and agonist ACh with potentiator Ca(2+), to give insight into the conformatio

61 nel open probability, and the dual corrector/potentiator CFFT-001 similarly disrupt interactions betw

62 rted by us for binding of the dual corrector-potentiator CFFT-001 to NBD1 (Hudson et al., 2012), sugg

63 ke firing rate was increased by the GluN2C/D potentiator CIQ and decreased by the GluN2C/D antagonist

64 ning, we infused the GluN2C/GluN2D-selective potentiator CIQ bilaterally into the basolateral amygdal

65 man subject, we speculate that corrector and potentiator combinations may have therapeutic efficacy i

66 Corrector and potentiator combinations were tested in primary cultures

67 h potentiator-only, corrector-only, and dual potentiator-corrector activities were found.

68 Previous studies showed that the AMPAR potentiators cyclothiazide and 4-[2-(phenylsulfonylamino

69 istent with these findings, an AMPA receptor potentiator delivered into the NAc decreases pain-induce

70 The dihydroisoxazole (DHI) series of AMPAR potentiators described herein originated from the identi

71 fonamides represent the first mGlu2 receptor potentiators discovered.

72 d membrane localization of CFTR, and/or CFTR potentiators, drugs that increase channel gating, to rea

73 nor previously identified allosteric mGluR1 potentiators [e.g., (S)-2-(4-fluorophenyl)-1-(toluene-4-

74 However, both a CFTR corrector and potentiator enhanced activity of protein variants genera

75 2,2',3,5'6-pentachlorobiphenyl; a potent RyR potentiator), enhanced synchronized Ca(2+) oscillations

76 sted, the most potent activator (E(act)) and potentiator (F(act)) produced large and more sustained C

77 nt at 0 Ca(2+), whereas tetrazolylbenzamide "potentiators" (F(act)) were not active at 0 Ca(2+) but r

78 antagonist GYKI-53655 displaces binding of a potentiator from brain receptors but not from recombinan

79 t with potentiators in the cocrystal disrupt potentiator function.

80 -5-methyl-4-isoxazolepropionic acid receptor potentiators has been identified using rational and stru

81 VX-770, a CFTR potentiator, has been shown to increase the activity of

82 acid (R-mTFD-MPAB), an anesthetic and GABAAR potentiator, has been shown to inhibit Torpedo alpha2bet

83 nt and stereoselective anesthetic and GABAAR potentiator, has identified a second class of intersubun

84 ("correctors") or chloride channel gating ("potentiators") have been discovered and are in clinical

85 ology of VX-770, an orally bioavailable CFTR potentiator in clinical development for the treatment of

86 potent pyridothiadiazine-type AMPA receptor potentiator in vitro, whereas the 7-chloro-substituted c

87 ide conductance was seen with correctors and potentiators in homozygous DeltaF508 cells, increased ch

88 g the binding affinities of subsequent AMPAR potentiators in rat brain homogenate, and PF-04701475 (8

89 int mutations of residues that interact with potentiators in the cocrystal disrupt potentiator functi

90 st example of the efficacy of mGlu2 receptor potentiators in these models.

91 combination with ivacaftor (VX-770), a CFTR potentiator, in patients 12 years of age or older who ha

92 trial to evaluate ivacaftor (VX-770), a CFTR potentiator, in subjects 12 years of age or older with c

93 tural classes of mGluR5-selective allosteric potentiators, including CDPPB, share a common binding si

94 s transmembrane conductance regulator (CFTR) potentiator, is approved for the treatment of patients w

95 ow residual function and respond to the CFTR potentiator ivacaftor in vitro, whereas ivacaftor alone

96 tment of G551D patients with the ion channel potentiator ivacaftor resulted in normalized neutrophil

97 cules, the CFTR corrector lumacaftor and the potentiator ivacaftor, are now used clinically to treat

98 nation with the corrector lumacaftor and the potentiator ivacaftor, it showed an additive effect, as

99 ivity of the mutants was rescued by the CFTR potentiator, ivacaftor (VX-770).

100 fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770/Kalydeco, Vertex Pharmace

101 Application of potentiators known to increase P(o) of DeltaF508 CFTR ch

102 'High-impact' AMPAR potentiators like PF-04958242 may have a role in the tre

103 a muscarinic acetylcholine receptor (mAChR) potentiator, LY2119620 (3-amino-5-chloro-N-cyclopropyl-4

104 also suggest that structurally diverse M(1) potentiators may act by distinct mechanisms and differen

105 rotein similar to the macrophage infectivity potentiator (Mip) proteins of Legionella pneumophila and

106 imerization domain of macrophage infectivity potentiator (Mip) proteins, which are proteins with pept

107 Macrophage infectivity potentiators (Mips) are a group of virulence factors enc

108 The single amino acid "P" (potentiator) mutation in the holoenzyme component GAL11

109 Recently, it was reported that the approved potentiator N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-

110 However, another mGluR5 potentiator, N-{4-chloro-2-[(1,3-dioxo-1,3-dihydro-2H-is

111 The twitch potentiator nitrate was shown to increase myoplasmic [Ca

112 Cyclothiazide (CTZ), a potentiator of AMPAR, revealed slowly rising AMPA EPSCs

113 has suggested that its product may act as a potentiator of another sex determination gene, tra-2.

114 Expression of GGT1 has been implicated as a potentiator of asthma, cardiovascular disease, and cance

115 oprotein, a powerful inflammatory signal and potentiator of atherosclerosis.

116 s contain the Th1-type cytokine IFN-gamma, a potentiator of atherosclerosis.

117 nd 2 (MRS 2219), was found to be a selective potentiator of ATP-evoked responses at rat P2X1 receptor

118 Development of a rationally designed potentiator of cancer chemotherapy, via inhibition of Bc

119 at Siva-1 or its SAH region can be used as a potentiator of cisplatin-based chemotherapy.

120 ic ether found in plant essential oils, as a potentiator of CPT cytotoxicity in Tdp1 deficient but no

121 lopment candidate with in vivo efficacy as a potentiator of deoxyribonucleic acid (DNA) damaging chem

122 g that 5-Aza-CdR should be investigated as a potentiator of IFN responsiveness in certain IFN-resista

123 ker for obesity-induced ATM infiltration and potentiator of interleukin-4 responses and point toward

124 Our study suggests that arsenic might be a potentiator of manganese toxicity.

125 , whereas a previously identified allosteric potentiator of mGluR1 has the opposite effect.

126 arboxamide (PHCCC) is a selective allosteric potentiator of mGluR4.

127 in vivo behavioral effects of an allosteric potentiator of mGluRs and suggest that potentiation of m

128 Our results establish that CMPI is a potent potentiator of nAChRs containing analpha4:alpha4 subunit

129 both an inhibitor of AChE and an allosteric potentiator of nAChRs, had similar effects.

130 A novel role for L1 as a potentiator of neuronal cell migration to extracellular

131 ticle, we identify a novel subunit-selective potentiator of NMDA receptors containing the NR2C or NR2

132 ither an inhibitory neurotransmitter or as a potentiator of NMDA-dependent excitatory neurotransmissi

133 that, in combination with Pax9, it acts as a potentiator of Pax9-induced Bmp4 transactivation.

134 tenin signaling has emerged as a significant potentiator of pluripotency: increases in the levels of

135 that Rap1 can act as either a repressor or a potentiator of Ras effector signals, depending on CD45 i

136 , raising the possibility that the nonsterol potentiator of reductase regulation is a geranylgeranyla

137 lacks allosteric agonist activity but acts a potentiator of responses to acetylcholine.

138 an unexpected role of zinc as an allosteric potentiator of small-molecule-induced activation of GPR3

139 or the prevention of cerebral ischemia, as a potentiator of statin anticancer activity.

140 The most likely potentiator of stroke risk in patients with cryptogenic

141 ll type 2 (Th2) cytokine best described as a potentiator of Th2 memory responses.

142 ated Gene 4 (PAGE4) is an IDP that acts as a potentiator of the Activator Protein-1 (AP-1) transcript

143 nctions and identified it to be an important potentiator of the antiproliferative effects of 9-cis-RA

144 Ivacaftor is a potentiator of the CFTR chloride channel and is in world

145 Ivacaftor is a potentiator of the cystic fibrosis transmembrane conduct

146 c acid (BQCA), a highly selective allosteric potentiator of the M(1) mAChR.

147 cuit, suggesting that MEF2C might serve as a potentiator of the transcriptional pathways affected in

148 -carboxylate), acts as a positive allosteric potentiator of Torpedo nACh receptor (nAChR) and binds t

149 gest that Finb/RREB-1 should be considered a potentiator of transcription, representing a distinct ca

150 genesis, and interleukin-1beta (IL-1beta), a potentiator of VEGF, were detected within 12 and 6 h, re

151 ds are among the most potent and efficacious potentiators of activation of GABA(A) receptors.

152 mes have been widely investigated for use as potentiators of anticancer therapies and as inhibitors o

153 pathogenesis of disease both as triggers and potentiators of beta-cell destruction.

154 on evaluating activity as monotherapy and as potentiators of chemotherapy.

155 re currently under clinical investigation as potentiators of cytotoxic chemotherapy and demonstrate p

156 dentified six novel classes of high affinity potentiators of defective Delta F508-CFTR Cl- channel ga

157 e Delta F508-CFTR processing, small molecule potentiators of defective Delta F508-CFTR gating may be

158 Other potentiators of GABA(A) receptors, including benzodiazep

159 -20-one (tetrahydrodeoxycorticosterone), all potentiators of GABA(A)Rs, inhibited the GABA-elicited c

160 Neuroactive steroids are efficacious potentiators of GABA-A receptors.

161 dent of IL-12 and IL-18, the well-documented potentiators of IFN-gamma expression, and is not produce

162 DNA-PK IC = 8 nM) with promising activity as potentiators of ionizing radiation-induced cytotoxicity

163 The role of bile acids as hormones and potentiators of liver cancer is also emerging.

164 Additionally, potentiators of mGlu3 may be useful in alleviating prefr

165 These data suggest that allosteric potentiators of mGluR1 act at a site that is distinct fr

166 nt class of small molecule subunit-selective potentiators of NMDA receptors.

167 e less apparent, carvacrol and thymol act as potentiators of responses evoked by submaximal concentra

168 entially inert to highly efficacious (strong potentiators of single-channel and macroscopic peak resp

169 covery of a new class of positive allosteric potentiators of the metabotropic glutamate receptor 2 (m

170 The strongest potentiators of the trigeminal response were carbonyl co

171 e designed experiments to develop allosteric potentiators of this key prostaglandin receptor.

172 ls that support specific bacterial agents as potentiators of tumorigenesis-including Fusobacterium nu

173 Positive allosteric modulators ("potentiators") of alpha-amino-3-hydroxy-5-methyl-4-isoxa

174 that act as positive allosteric modulators (potentiators) of metabotropic glutamate receptor (mGluR)

175 ompared with the use of agonists, allosteric potentiators offer potential advantages such as temporal

176 Stargazin also enhances the effect of AMPAR potentiators on channel deactivation.

177 Compounds with potentiator-only, corrector-only, and dual potentiator-c

178 Binding of spermine, an allosteric potentiator, opens the amino-terminal domain cleft of bo

179 by 8-fold, and did not show any significant potentiator or antagonist activity at other mGluR subtyp

180 ne remained an inhibitor, transformed into a potentiator, or converted to inhibitor and potentiator b

181 ing aged apoE4-KI mice with a GABAA receptor potentiator pentobarbital (PB) before and during behavio

182 g aged apoE4-KI mice with the GABAA receptor potentiator pentobarbital (PB) for 4 weeks before and du

183 eritoneal injections of the GABA(A) receptor potentiator pentobarbital at 20 mg/kg for 4 weeks rescue

184 roinjections of the allosteric AMPA receptor potentiator PEPA during the first 5 days of extinction t

185 The current study assessed whether the AMPAR potentiator PF-04958242 would attenuate ketamine-induced

186 k demonstrates that stargazin controls AMPAR potentiator pharmacology, which has important implicatio

187 ne hydrogen maleate] or the GABA(A) receptor potentiator phenobarbital, which mimics components of th

188 ,2',3,5'6-pentachlorobiphenyl), a potent RyR potentiator, phenocopies the dendrite-promoting effects

189 eptor in the presence of the alpha7-specific potentiator PNU-120596 (PNU).

190 ", normalizing DeltaF508-CFTR targeting) and potentiator ("Po", normalizing DeltaF508-CFTR channel ga

191 Furthermore, the GluN2A/B-selective potentiator (pregnenolone sulfate) and the GluN2C/D-sele

192 al. (2017) show that Wnts and Wnt signaling potentiator R-spondins have non-interchangeable roles.

193 s transmembrane conductance regulator (CFTR) potentiator recently approved for patients with CF age 6

194 In rats and nonhuman primates (NHP), AMPAR potentiators reduce spatial working memory deficits caus

195 A recombinant macrophage infectivity potentiator (rMIP) protein of Neisseria meningitidis ind

196 dict that glycans at GluN1-N440 might play a potentiator role in NMDARs.

197 Several novel potentiator scaffolds were identified with efficacy comp

198 AMPAR potentiators slow channel deactivation and desensitizati

199 We suggest that the potentiators slow deactivation by stabilizing the clamsh

200 o afford adsorption of small molecule immune potentiator (SMIP) onto alum, thereby enhancing co-deliv

201 ed the utility of a small molecule corrector/potentiator strategy, as used for DeltaF508-CFTR, to pro

202 Possible approaches for developing CFTR potentiators targeting site 1 will be discussed.

203 onic acid), a substrate-selective allosteric potentiator that augments 2-AG oxygenation by up to 3.5-

204 improved by replacement of Ivacaftor with a potentiator that does not interfere with corrector actio

205 R to the cell surface, and ivacaftor, a CFTR potentiator that enhances chloride transport of CFTR on

206 ical corrector, which helps CFTR fold, and a potentiator that increases CFTR channel activity.

207 od of overcoming such resistance is to use a potentiator that is capable of neutralizing the antiapop

208 ies represents the first class of allosteric potentiators that are selective for diheteromeric GluN2C

209 ivity analysis identified several classes of potentiators that do not impair corrector action, includ

210 t the identification and characterization of potentiators that do not interfere with F508-CFTR stabil

211 A panel of CFTR correctors and potentiators that increased DeltaF508-CFTR maturation or

212 benzo-1,4-dioxan-10-one), two AMPA receptor potentiators that preferentially slow AMPA receptor deac

213 CF patients under corrector-potentiator therapy, which enhances CFTR transport to th

214 r" to improve its cellular processing and a "potentiator" to improve its chloride channel function.

215 ucted a screen of 20,000 compounds for KCNQ2 potentiators using rubidium flux combined with atomic ab

216 mutation K1250A or pretreating with the CFTR potentiator VX-770 (Ivacaftor) imparted resistance to in

217 channel openings, background mutations or a potentiator was used to increase open duration.

218 ds were developed and their activity as AMPA potentiators was characterized.

219 Quinolinone-3-carboxamide 1, a novel CFTR potentiator, was discovered using high-throughput screen

220 reduced potentiating steroids; 5beta-reduced potentiators were only weakly affected.

221 These potentiators were shown to have no effect in the absence

222 bunit-specific NMDA receptor antagonists and potentiators were used to identify which GluN2 subunits

223 been shown to be a safe and effective immune potentiator when administered therapeutically.

224 analogue library synthesis approach provided potentiators with excellent potency and selectivity for

225 To identify novel correctors and potentiators with potentially greater efficacy on CFTR12

226 the need for appropriate delivery of immune potentiators with several 'delivery system' adjuvants su