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1 their role as 'delivery systems' or 'immune potentiators'.
2 eptor subunit 1 sensitive to both classes of potentiator.
3 rection of modulation, rendering 5beta-DHP a potentiator.
4 properties of this series as a biased GluN2 potentiator.
5 ewly-described role of elexacaftor as a CFTR potentiator.
6 X-770; Kalydeco), a clinically approved CFTR potentiator.
7 ted by ivacaftor, a clinically approved CFTR potentiator.
8 do[4,3-b]indole core as a novel chemotype of potentiators.
9 acid type A receptors (GABAARs) rather than potentiators.
10 therapeutic benefits of CFTR correctors and potentiators.
11 ing-fused thiadiazine dioxides class of AMPA potentiators.
12 eening for mGluR5 agonists, antagonists, and potentiators.
13 closely related to their potencies as mGluR5 potentiators.
14 ity of multiple classes of allosteric mGluR1 potentiators.
15 ation of small-molecule insulin mimetics and potentiators.
16 collection for insulin-receptor agonists and potentiators.
17 s for the development of insulin mimetics or potentiators.
18 ecular mechanism of action for AMPA receptor potentiators.
19 siveness to glucose and several of its known potentiators.
20 he development of antibiotics and antibiotic potentiators.
21 and remarkably, can convert inhibitors into potentiators.
22 eral roles for SMAD2/3 as cell-reprogramming potentiators.
23 of tricyclic sulfonamides as allosteric GlyR potentiators.
24 sphorylation and binding of chloride channel potentiators.
25 ew chemotype to the existing classes of CFTR potentiators.
26 n combination with small-molecule correctors/potentiators.
27 the range of CFTR mutations benefitted by co-potentiators, 14 CF-associated CFTR mutations were studi
28 lifetime, and sensitivity to the allosteric potentiator 3-[3-(3-pyridinyl)-1,2,4-oxadiazol-5-yl]benz
29 s of both the allosteric antagonist MPEP and potentiators 3,3'-difluorobenzaldazine and 3-cyano-N-(1,
30 es the binding affinity of the AMPA receptor potentiator [(3)H]-LY450295 and confers sensitivity to d
31 nenolone sulfate) and the GluN2C/D-selective potentiator [(3-chlorophenyl)(6,7-dimethoxy-1-((4-methox
32 It has been suggested that two allosteric potentiators, 3,3'-difluorobenzaldazine and 3-cyano-N-(1
33 ructural optimization provided highly potent potentiator 32 (AM-3607), which was cocrystallized with
35 revealed 6 compounds with dual corrector and potentiator activities and 13 compounds with only potent
36 ar EC(50) for DeltaPhe508-CFTR corrector and potentiator activities by short-circuit current assay.
46 and ivacaftor/tezacaftor brought together a potentiator and a class 1 corrector for F508del homozygo
50 regulate the pharmacology of allosteric AMPA potentiators and antagonists in the cerebellum and hippo
52 address a different cellular CF defect from potentiators and correctors, our inhibitors provide an a
54 in, in contrast to the uncharged, allosteric potentiators and inhibitors that also bind within the de
56 d structural features of active and inactive potentiators and successfully predicting the activity of
57 are likely to complicate efforts to identify potentiators and/or correctors of the deltaF508 defect.
58 be recovered by pharmaceutical modulators ("potentiators" and "correctors"), but DeltaF508-CFTR can
59 linical trials combining ivacaftor (a gating potentiator) and lumacaftor (a folding corrector) have p
60 ting CFTR-one boosting ion-channel function (potentiators) and the other increasing plasma membrane d
63 r low potencies, previously described mGluR5 potentiators are not useful for functional studies in na
69 results obtained in previous series of AMPA potentiators belonging to 3,4-dihydro-2H-benzo- and 3,4-
72 nfers partial sensitivity of [(3)H]-LY450295 potentiator binding to displacement by non-competitive a
73 lyRalpha3cryst to afford the first described potentiator-bound X-ray cocrystal structure within this
74 st acetylcholine (ACh), and agonist ACh with potentiator Ca(2+), to give insight into the conformatio
75 nel open probability, and the dual corrector/potentiator CFFT-001 similarly disrupt interactions betw
76 rted by us for binding of the dual corrector-potentiator CFFT-001 to NBD1 (Hudson et al., 2012), sugg
78 ke firing rate was increased by the GluN2C/D potentiator CIQ and decreased by the GluN2C/D antagonist
79 ning, we infused the GluN2C/GluN2D-selective potentiator CIQ bilaterally into the basolateral amygdal
80 s II potentiator') was used with a classical potentiator ('Class I potentiator') such as VX-770 or GL
81 We previously introduced the concept of 'co-potentiators' (combination-potentiators) to rescue CFTR
82 man subject, we speculate that corrector and potentiator combinations may have therapeutic efficacy i
87 istent with these findings, an AMPA receptor potentiator delivered into the NAc decreases pain-induce
88 The dihydroisoxazole (DHI) series of AMPAR potentiators described herein originated from the identi
90 s should be considered in campaigns for CFTR potentiator discovery, and may enable the expansion of V
95 d membrane localization of CFTR, and/or CFTR potentiators, drugs that increase channel gating, to rea
96 nor previously identified allosteric mGluR1 potentiators [e.g., (S)-2-(4-fluorophenyl)-1-(toluene-4-
100 2,2',3,5'6-pentachlorobiphenyl; a potent RyR potentiator), enhanced synchronized Ca(2+) oscillations
101 ects of a novel low-molecular-weight TMEM16A potentiator (ETX001) were evaluated in human cell and an
102 sted, the most potent activator (E(act)) and potentiator (F(act)) produced large and more sustained C
103 nt at 0 Ca(2+), whereas tetrazolylbenzamide "potentiators" (F(act)) were not active at 0 Ca(2+) but r
104 c niche, suggesting a potential of GABAergic potentiators for pro-neurogenic or cell therapies of AD.
105 antagonist GYKI-53655 displaces binding of a potentiator from brain receptors but not from recombinan
107 -5-methyl-4-isoxazolepropionic acid receptor potentiators has been identified using rational and stru
108 h the recent introduction of CFTR correctors/potentiators has revolutionized the clinical management
110 acid (R-mTFD-MPAB), an anesthetic and GABAAR potentiator, has been shown to inhibit Torpedo alpha2bet
111 nt and stereoselective anesthetic and GABAAR potentiator, has identified a second class of intersubun
112 ("correctors") or chloride channel gating ("potentiators") have been discovered and are in clinical
113 cribe a potent small molecule sodium channel potentiator ICA00600232 that exhibits >1000-fold selecti
115 he amount of CFTR on the cell surface, while potentiators improve the gating function of the CFTR cha
116 ology of VX-770, an orally bioavailable CFTR potentiator in clinical development for the treatment of
117 with the combination of a CFTR corrector and potentiator in people with cystic fibrosis homozygous fo
118 potent pyridothiadiazine-type AMPA receptor potentiator in vitro, whereas the 7-chloro-substituted c
119 nhibition which was prevented by a GluN2C/2D potentiator in wildtype and GluN2C heterozygous mice but
122 ide conductance was seen with correctors and potentiators in homozygous DeltaF508 cells, increased ch
123 g the binding affinities of subsequent AMPAR potentiators in rat brain homogenate, and PF-04701475 (8
124 int mutations of residues that interact with potentiators in the cocrystal disrupt potentiator functi
126 combination with ivacaftor (VX-770), a CFTR potentiator, in patients 12 years of age or older who ha
127 trial to evaluate ivacaftor (VX-770), a CFTR potentiator, in subjects 12 years of age or older with c
128 tural classes of mGluR5-selective allosteric potentiators, including CDPPB, share a common binding si
129 s transmembrane conductance regulator (CFTR) potentiator, is approved for the treatment of patients w
130 ow residual function and respond to the CFTR potentiator ivacaftor in vitro, whereas ivacaftor alone
132 tment of G551D patients with the ion channel potentiator ivacaftor resulted in normalized neutrophil
133 cules, the CFTR corrector lumacaftor and the potentiator ivacaftor, are now used clinically to treat
135 nation with the corrector lumacaftor and the potentiator ivacaftor, it showed an additive effect, as
136 fibrosis transmembrane conductance regulator potentiator (ivacaftor), and a selective estrogen recept
138 fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770/Kalydeco, Vertex Pharmace
140 nation of the corrector, lumacaftor, and the potentiator, ivacaftor, partially rescues the defective
143 a muscarinic acetylcholine receptor (mAChR) potentiator, LY2119620 (3-amino-5-chloro-N-cyclopropyl-4
144 also suggest that structurally diverse M(1) potentiators may act by distinct mechanisms and differen
146 rotein similar to the macrophage infectivity potentiator (Mip) proteins of Legionella pneumophila and
148 imerization domain of macrophage infectivity potentiator (Mip) proteins, which are proteins with pept
151 Recently, it was reported that the approved potentiator N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-
156 has suggested that its product may act as a potentiator of another sex determination gene, tra-2.
157 Expression of GGT1 has been implicated as a potentiator of asthma, cardiovascular disease, and cance
160 nd 2 (MRS 2219), was found to be a selective potentiator of ATP-evoked responses at rat P2X1 receptor
161 he role of amyloids as a carrier for DNA and potentiator of autoimmune responses, and we propose a no
164 n contrast to exhaustion regulator TOX, as a potentiator of central memory differentiation of CAR T c
165 l properties of BIA as a BTB modulator and a potentiator of chemotherapy, supporting its further deve
167 ic ether found in plant essential oils, as a potentiator of CPT cytotoxicity in Tdp1 deficient but no
168 lopment candidate with in vivo efficacy as a potentiator of deoxyribonucleic acid (DNA) damaging chem
169 specifically that osmotic swelling acts as a potentiator of downstream signaling, not only for the be
171 g that 5-Aza-CdR should be investigated as a potentiator of IFN responsiveness in certain IFN-resista
172 ker for obesity-induced ATM infiltration and potentiator of interleukin-4 responses and point toward
176 in vivo behavioral effects of an allosteric potentiator of mGluRs and suggest that potentiation of m
177 on of a high throughput screening hit 6 as a potentiator of mutant human F508del and wild-type CFTR c
178 Our results establish that CMPI is a potent potentiator of nAChRs containing analpha4:alpha4 subunit
181 ticle, we identify a novel subunit-selective potentiator of NMDA receptors containing the NR2C or NR2
182 ither an inhibitory neurotransmitter or as a potentiator of NMDA-dependent excitatory neurotransmissi
184 tenin signaling has emerged as a significant potentiator of pluripotency: increases in the levels of
185 that Rap1 can act as either a repressor or a potentiator of Ras effector signals, depending on CD45 i
186 , raising the possibility that the nonsterol potentiator of reductase regulation is a geranylgeranyla
188 an unexpected role of zinc as an allosteric potentiator of small-molecule-induced activation of GPR3
192 ated Gene 4 (PAGE4) is an IDP that acts as a potentiator of the Activator Protein-1 (AP-1) transcript
193 nctions and identified it to be an important potentiator of the antiproliferative effects of 9-cis-RA
197 cuit, suggesting that MEF2C might serve as a potentiator of the transcriptional pathways affected in
198 exhibit enhanced levels of miR-92a (a known potentiator of the Wnt/beta-catenin pathway), and that t
199 -carboxylate), acts as a positive allosteric potentiator of Torpedo nACh receptor (nAChR) and binds t
200 gest that Finb/RREB-1 should be considered a potentiator of transcription, representing a distinct ca
201 genesis, and interleukin-1beta (IL-1beta), a potentiator of VEGF, were detected within 12 and 6 h, re
203 mes have been widely investigated for use as potentiators of anticancer therapies and as inhibitors o
206 re currently under clinical investigation as potentiators of cytotoxic chemotherapy and demonstrate p
207 dentified six novel classes of high affinity potentiators of defective Delta F508-CFTR Cl- channel ga
208 e Delta F508-CFTR processing, small molecule potentiators of defective Delta F508-CFTR gating may be
210 -20-one (tetrahydrodeoxycorticosterone), all potentiators of GABA(A)Rs, inhibited the GABA-elicited c
212 dent of IL-12 and IL-18, the well-documented potentiators of IFN-gamma expression, and is not produce
213 th a broader therapeutic window, were better potentiators of INH-mediated inhibition of an INH-resist
214 DNA-PK IC = 8 nM) with promising activity as potentiators of ionizing radiation-induced cytotoxicity
220 nthetic small molecules identified active co-potentiators of pyrazoloquinoline, piperidine-pyridoindo
221 e less apparent, carvacrol and thymol act as potentiators of responses evoked by submaximal concentra
222 entially inert to highly efficacious (strong potentiators of single-channel and macroscopic peak resp
223 covery of a new class of positive allosteric potentiators of the metabotropic glutamate receptor 2 (m
226 ls that support specific bacterial agents as potentiators of tumorigenesis-including Fusobacterium nu
229 that act as positive allosteric modulators (potentiators) of metabotropic glutamate receptor (mGluR)
230 ompared with the use of agonists, allosteric potentiators offer potential advantages such as temporal
233 opy structures of human CFTR in complex with potentiators: one with the U.S. Food and Drug Administra
236 by 8-fold, and did not show any significant potentiator or antagonist activity at other mGluR subtyp
237 ne remained an inhibitor, transformed into a potentiator, or converted to inhibitor and potentiator b
238 of the GluN2C-selective positive allosteric potentiator (PAM), PYD-106, the agonist-bound GluN1-2A-2
239 ing aged apoE4-KI mice with a GABAA receptor potentiator pentobarbital (PB) before and during behavio
240 g aged apoE4-KI mice with the GABAA receptor potentiator pentobarbital (PB) for 4 weeks before and du
241 eritoneal injections of the GABA(A) receptor potentiator pentobarbital at 20 mg/kg for 4 weeks rescue
242 roinjections of the allosteric AMPA receptor potentiator PEPA during the first 5 days of extinction t
243 The current study assessed whether the AMPAR potentiator PF-04958242 would attenuate ketamine-induced
244 k demonstrates that stargazin controls AMPAR potentiator pharmacology, which has important implicatio
245 ne hydrogen maleate] or the GABA(A) receptor potentiator phenobarbital, which mimics components of th
246 ,2',3,5'6-pentachlorobiphenyl), a potent RyR potentiator, phenocopies the dendrite-promoting effects
248 structure determined in the presence of the potentiator PNU-120596 was consistent with an activated
249 ", normalizing DeltaF508-CFTR targeting) and potentiator ("Po", normalizing DeltaF508-CFTR channel ga
251 al. (2017) show that Wnts and Wnt signaling potentiator R-spondins have non-interchangeable roles.
252 s transmembrane conductance regulator (CFTR) potentiator recently approved for patients with CF age 6
253 In rats and nonhuman primates (NHP), AMPAR potentiators reduce spatial working memory deficits caus
261 o afford adsorption of small molecule immune potentiator (SMIP) onto alum, thereby enhancing co-deliv
262 ed the utility of a small molecule corrector/potentiator strategy, as used for DeltaF508-CFTR, to pro
265 tance by up to 8-fold was observed when a co-potentiator (termed 'Class II potentiator') was used wit
266 onic acid), a substrate-selective allosteric potentiator that augments 2-AG oxygenation by up to 3.5-
267 improved by replacement of Ivacaftor with a potentiator that does not interfere with corrector actio
268 R to the cell surface, and ivacaftor, a CFTR potentiator that enhances chloride transport of CFTR on
270 zed CFTR protein, ivacaftor serves as a CFTR potentiator that increases the open probability of CFTR
271 od of overcoming such resistance is to use a potentiator that is capable of neutralizing the antiapop
272 ies represents the first class of allosteric potentiators that are selective for diheteromeric GluN2C
273 ivity analysis identified several classes of potentiators that do not impair corrector action, includ
274 t the identification and characterization of potentiators that do not interfere with F508-CFTR stabil
276 benzo-1,4-dioxan-10-one), two AMPA receptor potentiators that preferentially slow AMPA receptor deac
279 rting points for developing novel antibiotic potentiators, this method could be expanded to other col
280 r" to improve its cellular processing and a "potentiator" to improve its chloride channel function.
281 he concept of 'co-potentiators' (combination-potentiators) to rescue CFTR function in some minimal fu
282 e secretion in our assay than ivacaftor, the potentiator treatment currently available to these patie
284 ucted a screen of 20,000 compounds for KCNQ2 potentiators using rubidium flux combined with atomic ab
285 mutation K1250A or pretreating with the CFTR potentiator VX-770 (Ivacaftor) imparted resistance to in
288 rved when a co-potentiator (termed 'Class II potentiator') was used with a classical potentiator ('Cl
290 Quinolinone-3-carboxamide 1, a novel CFTR potentiator, was discovered using high-throughput screen
293 bunit-specific NMDA receptor antagonists and potentiators were used to identify which GluN2 subunits
295 report that cathelicidin is a powerful Th17 potentiator which enhances aryl hydrocarbon receptor (AH
296 analogue library synthesis approach provided potentiators with excellent potency and selectivity for
299 the need for appropriate delivery of immune potentiators with several 'delivery system' adjuvants su
300 tic efficacy, and they can act as antibiotic potentiators, with a mechanism of action orthogonal to s