ライフサイエンスコーパス: allosteric modulation

1 nerated significant interest in CB1 receptor allosteric modulation.

2 linker, consistent with its contribution to allosteric modulation.

3 value alpha < 1, thus indicating a negative allosteric modulation.

4 icking, channel gating, agonist potency, and allosteric modulation.

5 changes at position E172C in the absence of allosteric modulation.

6 mmaMet-299) likely to be a site for positive allosteric modulation.

7 ructural determinant in NMDAR activation and allosteric modulation.

8 issociation kinetics, ligand specificity and allosteric modulation.

9 (GABA(A)) receptor during channel gating and allosteric modulation.

10 ch may render them particularly sensitive to allosteric modulation.

11 esidues critical for receptor activation and allosteric modulation.

12 for CB1R allosteric activation and positive allosteric modulation.

13 ding, and also long alkyl amides are without allosteric modulation.

14 ral correlates of activation, antagonism and allosteric modulation.

15 petitive antagonists; both drugs act through allosteric modulation.

16 ors (GPCRs), are biological targets prone to allosteric modulation.

17 GABA(A)Rs in response to agonist exposure or allosteric modulation.

18 es reveal the atomistic mechanism underlying allosteric modulation.

19 L247T mutant and may be relevant to type-II allosteric modulation.

20 by binding to active sites or exosites or by allosteric modulation.

21 idence for a purely efficacy-driven positive allosteric modulation.

22 he pyrrolidinyl ring is not required for CB1 allosteric modulation.

23 o investigate the structural determinants of allosteric modulation.

24 eptor (GABA(A)R) contributes to neurosteroid allosteric modulation.

25 with different headgroups display a range of allosteric modulation.

26 to form an intracellular 'skirt' involved in allosteric modulation.

27 nderstanding of the structural basis of mGlu allosteric modulation.

28 icity of drug action that can be provided by allosteric modulation across a GPCR homodimeric interfac

29 g allosteric agonism in addition to positive allosteric modulation (ago-PAMs).

30 ough negative (alpha6beta1delta) or positive allosteric modulation (alpha4beta2delta, alpha6beta2,3de

31 h dimer modeling provides insights about the allosteric modulation and activation mechanism of class

32 The concepts of allosteric modulation and biased agonism are revolutioni

33 thus provides a robust tool for probing PKL allosteric modulation and fills a key gap in target enga

34 foundation for mechanisms of ligand-gating, allosteric modulation and ion permeation.

35 We examined the effects on allosteric modulation and ligand binding of the mutation

36 e binding process suggests opportunities for allosteric modulation and provides a structural foundati

37 Further issues discussed include allosteric modulation and the role of water molecules in

38 n the context of ligand binding, activation, allosteric modulation, and biased signaling.

39 echanisms, including competitive inhibition, allosteric modulation, and immune effector mechanisms.

40 f effects, ranging from positive to negative allosteric modulation, and includes compounds that do no

41 ons, intracellular interface remodeling, and allosteric modulation, and provide a mechanistic basis f

42 tile tools to investigate binding processes, allosteric modulation, and the oligomerization mechanism

43 of IgE structure, its resultant capacity for allosteric modulation, and the potential for ligand-indu

44 ectivity; mechanisms for desensitization and allosteric modulation; and mechanisms for partial agonis

45 l determinants for positive and negative BZD allosteric modulation are different.

46 , clearly showcasing the potential of A(2A)R allosteric modulation as a novel approach for efficient

47 and quantifying ligand-biased signaling and allosteric modulation at CB1Rs, revealing ligand-biased

48 y, we quantified ligand-biased signaling and allosteric modulation at CB1Rs.

49 ssociation of [(3)H]S-1 from the S1 site via allosteric modulation at S2.

50 confirm GL-I-54 and GL-II-73 exert positive allosteric modulation at the alpha2-, alpha3-, alpha5-GA

51 ing to unravel the mechanistic basis of GPCR allosteric modulation at the molecular level.

52 Biased agonism and positive allosteric modulation at the mu-opioid receptor have bee

53 ipophilic ligands, including a mechanism for allosteric modulation at the transmembrane subunit inter

54 We review the allosteric modulation, biased agonism, oligomerization,

55 d to influence receptor conformation through allosteric modulation, biased signaling, and selectivity

56 Biased GLP-1R agonists and small molecule allosteric modulation both influence GLP-1R palmitoylati

57 eptor activation, signaling, drug action and allosteric modulation, but so far cover only 13% of nono

58 d and tested for sensitivity to glycine, and allosteric modulation by alcohols.

59 ng periods of prolonged stimulation, whereas allosteric modulation by ATP may help to modulate intrac

60 f AMPA-type glutamate receptors (AMPARs) and allosteric modulation by auxiliary subunits, such as tra

61 The lack of additional, pathway-biased, allosteric modulation by BQCA was confirmed in genetical

62 Allosteric modulation by cis-(Z)-flupentixol involves a

63 played probe-dependent and pathway-dependent allosteric modulation by concentrations of zinc reported

64 )) side, convincingly disrupted the positive allosteric modulation by DS2.

65 0-one in the central nervous system, and its allosteric modulation by fluoxetine has been linked to t

66 d type A (GABA(A) )receptors are targets for allosteric modulation by general anesthetics.

67 e step-wise cleavages (processivity) and its allosteric modulation by heterocyclic y-modulatory compo

68 s residues of the GABA(A) alpha-3 subunit in allosteric modulation by isoflurane.

69 amily" of ion channels, and are sensitive to allosteric modulation by n-alcohols such as ethanol and

70 Mutation at TM2(D79N) reduces allosteric modulation by Na(+) and receptor activation m

71 llustrates the possibility that the locus of allosteric modulation by PD 81,723 may be manifest via a

72 ith delta subunit also affected the negative allosteric modulation by pregnenolone sulfate.

73 and kinetically distinct from rapid positive allosteric modulation by PregS.

74 critical role in channel gating by GABA and allosteric modulation by propofol.

75 n a way which is subjected to structural and allosteric modulation by the weak zinc-binding C-termina

76 Thrombin undergoes allosteric modulation by thrombomodulin (TM) that result

77 Exploiting G-protein biased CB1R-allosteric modulation can offer safer therapeutic candid

78 ctivation by allosteric agonism, rather than allosteric modulation, could be responsible for the adve

79 Strikingly, these allosteric modulations disappear on agonist and antagoni

80 application of concepts such as signal bias, allosteric modulation, dual agonism, polymorphic recepto

81 rtions of them may have negative or positive allosteric modulation effects on the function of their "

82 irectly inhibit the proteolysis of MMP-9 via allosteric modulation exclusively at the ligand specific

83 nal suitability and therapeutic potential of allosteric modulation for correcting these deficits.

84 rovide molecular insights into mechanisms of allosteric modulation for glutamate transporters.

85 for these sites, combined with differential allosteric modulation, gives rise to a complex interplay

86 Over the past 20 years, our understanding of allosteric modulation has grown significantly, and numer

87 es a highly sensitive yardstick to probe the allosteric modulation in contrast to the traditionally u

88 r findings provide a structural mechanism of allosteric modulation in mGluR2 and suggest possible str

89 c receptors and sheds light on mechanisms of allosteric modulation in nAChRs, especially the subtle d

90 pecific electrostatic interactions drive the allosteric modulation in the PDZ3 domain protein.

91 he absence of GABA and demonstrated positive allosteric modulation in the presence of GABA, whereas b

92 further substantiating a multisite model of allosteric modulation in this family of ion channels.

93 ssing native Y4R, demonstrating Y4R positive allosteric modulation in vitro.

94 XCR4 at the CXCL12 binding pocket suggesting allosteric modulation, in accordance with our electrophy

95 t alterations in either thermal stability or allosteric modulation increase starch synthesis.

96 and stereochemistry can affect the degree of allosteric modulation, indicating an unforeseen selectiv

97 with native rhodopsin reveal a mechanism of allosteric modulation involving extracellular loop 2 and

98 Allosteric modulation is a central mechanism for metabol

99 Allosteric modulation is a mechanism for modifying pharm

100 GPCR allosteric modulation is an innovative targeting approac

101 must exist in the drug-bound enzyme and that allosteric modulation is effected via the alteration of

102 e role of intracellular domains in mediating allosteric modulation is largely unknown.

103 tes that the initial phase of rapid positive allosteric modulation is not a first step in NMDAR upreg

104 This allosteric modulation may be direct, involving binding t

105 eceptor, which provides new insight into how allosteric modulation may be transmitted between the two

106 Allosteric modulation may pave an alternative way to ini

107 Allosteric modulation may yield a change in the activity

108 d range of recent findings point to a shared allosteric modulation mechanism among these proteins, wh

109 nditions, but remained sensitive to negative allosteric modulation [N-(2-hydroxy-3-(2-cyano-3-chlorop

110 s strongly support the hypothesis that mGluR allosteric modulation occurs via stabilization of differ

111 gonist diphenyleneiodonium chloride revealed allosteric modulation of 45 binding.

112 the biological and behavioral mechanisms of allosteric modulation of a receptor important in several

113 ver, we identified the binding sites and the allosteric modulation of ACKR3 upon beta-arrestin 1 bind

114 ion by sevoflurane results from the positive allosteric modulation of activation gating.

115 Allosteric modulation of adenosine A1 receptors (A1ARs)

116 ional model of allosterism that accounts for allosteric modulation of affinity, efficacy, and alloste

117 In this study, allosteric modulation of agonist binding and function at

118 Achievable strategies include the negative allosteric modulation of AhR and the disruption of AhR-p

119 emotional responses by reducing the positive allosteric modulation of Allo at GABA(A) receptors in co

120 trast to direct agonist activation, positive allosteric modulation of alpha7 nAChRs would deliver the

121 r with either agonist activation or positive allosteric modulation of alpha7 nAChRs.

122 in gating and represents a hub for powerful allosteric modulation of AMPA receptor function that can

123 .c.v. infusion, we demonstrate that positive allosteric modulation of AMPA receptors by PAM-AMPA trea

124 Our findings suggest that positive allosteric modulation of AMPA receptors restores synapti

125 Our findings suggest that positive allosteric modulation of AMPA receptors restores synapti

126 ify glutamatergic signaling through positive allosteric modulation of AMPA receptors, by the use of a

127 However, allosteric modulation of ASCT2 via non-competitive inhib

128 vity, and five produced significant positive allosteric modulation of atropine-reversible, direct-ago

129 llular loop 2 of the B1R results in positive allosteric modulation of B1R signaling, and disruption o

130 [Sar(1),Ile(4),Ile(8)]-AngII exerts lateral allosteric modulation of B2 receptor signaling by bindin

131 that alternative core packing and consequent allosteric modulation of binding interfaces could be use

132 conclude that rifamycins do not function by allosteric modulation of binding of Mg(2+) to the RNAP a

133 et al. proposed that rifamycins function by allosteric modulation of binding of Mg(2+) to the RNAP a

134 ansmembrane domains 2 and 3 are critical for allosteric modulation of both GABA(A) and glycine recept

135 nding competition with NAD(+) followed by an allosteric modulation of bound PARPi.

136 ith a domain interface model for binding and allosteric modulation of Ca2+ channel activity by DHPs.

137 ional studies demonstrated that MCV1 acts by allosteric modulation of calcineurin.

138 Allosteric modulation of cannabinoid receptor type 1 (CB

139 l distorted guide-target duplex geometry and allosteric modulation of Cas9 conformation.

140 Allosteric modulation of catalysis kinetics is prevalent

141 een associated with substrate positioning or allosteric modulation of catalytic activity, but its cel

142 Additionally, positive allosteric modulation of CB1 by anionic phospholipids is

143 Positive allosteric modulation of CB1-receptor signaling shows pr

144 al requirements of indole-2-carboxamides for allosteric modulation of CB1: a critical chain length at

145 no inherent agonism but maintained positive allosteric modulation of CCL3 binding.

146 Together our findings suggest that the allosteric modulation of channel gating involves distinc

147 tic specificity and offers new insights into allosteric modulation of channel gating.

148 rather with the loss of stargazin-associated allosteric modulation of channel gating.

149 ng site may represent a common mechanism for allosteric modulation of class A GPCRs.

150 sms that contribute to positive and negative allosteric modulation of classical ligand binding, inclu

151 ant new tool compound for the exploration of allosteric modulation of COX enzymes and their role in e

152 For the G-protein-uncoupled receptor, allosteric modulation of CRF binding was correlated with

153 chemokine CXCL14 synergizes with CXCL12 via allosteric modulation of CXCR4.

154 sms of fast inhibitory neurotransmission and allosteric modulation of Cys-loop receptors.

155 e our understanding of a multisite model for allosteric modulation of Cys-loop receptors.

156 aenorhabditis elegans as a new tool to study allosteric modulation of DAT and its behavioral conseque

157 More broadly, our findings demonstrate allosteric modulation of DAT as a behavior modifying str

158 Agents that exhibit noncompetitive, allosteric modulation of DAT remain an important topic o

159 swimming-induced paralysis through a direct allosteric modulation of DAT-1.

160 de-binding lectins, exhibit subunit-specific allosteric modulation of desensitization of recombinant

161 23 and 26) is consistent with noncompetitive allosteric modulation of dopamine signaling in the extra

162 bout whether this equivalence extends to the allosteric modulation of DREADDs by small molecules.

163 Activation or positive allosteric modulation of DUBs could provide therapeutic

164 ic approach to evaluate the role of positive allosteric modulation of each of the four diazepam-sensi

165 rkB (tyrosine kinase B) and drive a positive allosteric modulation of endogenous BDNF (brain-derived

166 ole of PH domains in regulating catalysis by allosteric modulation of enzyme structure.

167 us have suggested that this effect involves allosteric modulation of factor IXa.

168 Allosteric modulation of G protein-coupled receptors (GP

169 Allosteric modulation of G protein-coupled receptors (GP

170 Allosteric modulation of G protein-coupled receptors rep

171 Allosteric modulation of G-protein-coupled receptors rep

172 f fluoxetine or fluvoxamine via its positive allosteric modulation of GABA type A receptors.

173 erexcitability can be attenuated by positive allosteric modulation of GABA(A) receptors (GABA(A)Rs).

174 naplon produces an anxiolytic action through allosteric modulation of GABA(A) receptors.

175 ons in SI mice appears to be elicited by the allosteric modulation of GABA(A)-Rs overexpressing alpha

176 Conversely, in the late phase, negative allosteric modulation of GABA(A)R can correct the subopt

177 Moreover, negative allosteric modulation of GABAA receptors impaired social

178 ort the involvement of the M4 segment in the allosteric modulation of GABArho1 by DPA.

179 ma2 and gamma8, we could entirely remove all allosteric modulation of GluA2, without affecting format

180 Negative allosteric modulation of GluN2B subunit-containing NMDA

181 Allosteric modulation of GPCRs has initiated a new era o

182 ss of positive modulators and establish that allosteric modulation of hERG channel function through l

183 s of hmGluR3, completely eliminated LY487379 allosteric modulation of hmGluR2.

184 In this study, the allosteric modulation of human A(3) adenosine receptors

185 3's regulatory effects may stem in part from allosteric modulation of IF2-GAC interactions.

186 ion of a ubiquitin-dependent pathway through allosteric modulation of its E3 activity by small compou

187 mulated the chaperone functions of Hsp90 via allosteric modulation of its N-terminal domain, responsi

188 ing the direction of information flow during allosteric modulation of its nucleotide-dependent intrin

189 ings reveal the importance of exosite-driven allosteric modulation of IXa function and new strategies

190 suggest that sulfhydration of SUR2B induces allosteric modulation of K(ATP) currents in colonic infl

191 lectivity, providing a mechanistic basis for allosteric modulation of ligand selectivity.

192 lecules act on synaptic transmission via the allosteric modulation of ligand-gated chloride channels,

193 neurotransmitter systems, drugs that provide allosteric modulation of ligand-gated ion channels or G-

194 s provide preliminary evidence that positive allosteric modulation of M1 is sufficient to elicit chol

195 troduce concepts for partial efficacy at and allosteric modulation of MATs.

196 Here, we highlight allosteric modulation of metabolic enzymes as an attract

197 This review focuses on positive allosteric modulation of metabotropic glutamate 2 recept

198 Positive allosteric modulation of metabotropic glutamate receptor

199 Allosteric modulation of metabotropic glutamate receptor

200 Positive allosteric modulation of metabotropic glutamate subtype

201 In particular, the allosteric modulation of mGlu receptors represents a maj

202 re mGlu(5) NAM binding kinetics and negative allosteric modulation of mGlu(5) receptor internalizatio

203 measure ligand binding kinetics and negative allosteric modulation of mGlu(5) receptor internalizatio

204 Acute positive allosteric modulation of mGlu5 or inhibition of endocann

205 the mGlu5/eCB signaling complex, by positive allosteric modulation of mGlu5 or inhibition of endocann

206 These results support positive allosteric modulation of mGlu5, particularly with VU0409

207 tance to extinction was reversed by positive allosteric modulation of mGluR5 during extinction traini

208 These data indicate that positive allosteric modulation of mGluR5 receptors facilitates th

209 Conversely, positive allosteric modulation of mGluR5 results in the exacerbat

210 utral cooperativity, preventing the positive allosteric modulation of mGluRs by DFB as well as the ne

211 is study provides structural evidence on the allosteric modulation of MgNTP(2-) on the NS3 helicase a

212 Allosteric modulation of muscarinic acetylcholine recept

213 ning behaviors in zebrafish, suggesting that allosteric modulation of muscarinic receptor efficacy mi

214 the mechanisms of orthosteric activation and allosteric modulation of muscarinic receptors.

215 t insights into the activation mechanism and allosteric modulation of muscarinic receptors.

216 r-independent mechanisms (membrane dynamics, allosteric modulation of N-acyl phosphatidylethanolamine

217 ivation through the agonist binding site, an allosteric modulation of nAChR has also been described f

218 We are interested in the allosteric modulation of neuronal nicotinic acetylcholin

219 We are interested in the positive allosteric modulation of neuronal nicotinic acetylcholin

220 tructural requirements for the formation and allosteric modulation of NMDA receptor pores, we have re

221 Allosteric modulation of NR activity constitutes a promi

222 tection threshold in humans, suggesting that allosteric modulation of odorant receptors is perceptual

223 opioid agonism, multifunctional opioids, and allosteric modulation of opioid receptors.

224 However, the present negative allosteric modulation of P2X receptors is primarily limi

225 extracellular Ca(2+) Reciprocally, positive allosteric modulation of P2X4 (ivermectin) augmented ATP

226 ication and maintain segment balance through allosteric modulation of polymerase activity.

227 nhibitory neurotransmission through positive allosteric modulation of postsynaptic GABAA receptors, i

228 Instead, we suggest an allosteric modulation of prestin by Cl- and other anions

229 hich we have perturbed, likely contribute to allosteric modulation of prestin via interactions among

230 These results suggest that the allosteric modulation of protein function by isoflurane,

231 Allosteric modulation of protein function, wherein the b

232 ese interactions may provide a mechanism for allosteric modulation of receptor function.

233 eptors and vice versa, suggesting reciprocal allosteric modulation of receptors in the heterodimer.

234 We show that these key features of allosteric modulation of recombinant GluN1/2B/2D recepto

235 data of RT in various states, details of the allosteric modulation of RT dynamics by NNRTIs are lacki

236 In cells, negative allosteric modulation of SETDB1-mediated Akt methylation

237 provide insights into how substrate-coupled allosteric modulation of structure and dynamics facilita

238 including a conserved drug-binding site for allosteric modulation of substrate proteolysis.

239 A mechanism for interdomain allosteric modulation of substrate-binding is proposed.

240 Our study highlights the allosteric modulation of the activity and the conformati

241 annel complex in a binary fashion; one is an allosteric modulation of the alpha1 subunit function and

242 f 9-aminoacridine compounds that demonstrate allosteric modulation of the alpha1A- and alpha1B-adrene

243 esents a novel class of molecules capable of allosteric modulation of the alpha7 nAChRs.

244 ntity of the subunit mediating the direct or allosteric modulation of the antidepressant effect on GA

245 viously identified site involved in positive allosteric modulation of the bacterial homolog ELIC.

246 ch to interrogate both biased signalling and allosteric modulation of the beta(1)-adrenergic receptor

247 Allosteric modulation of the CaS receptor corrects disor

248 We found that allosteric modulation of the CNO-bound DREADD receptor i

249 ently to divalent cations and the effects of allosteric modulation of the cortical CHRM1 is reduced i

250 Positive allosteric modulation of the GABA(A) receptor (GABA(A)R)

251 GABA(A) receptor-mediated ionic currents via allosteric modulation of the GABA(A) receptor.

252 fect of selection for ethanol sensitivity on allosteric modulation of the GABA-A receptor.

253 s to increase Abeta42 production may reflect allosteric modulation of the gamma-secretase complex by

254 n determining the functional consequences of allosteric modulation of the Gly-R by alcohols.

255 re synthesized and tested for their positive allosteric modulation of the HCA(2) receptor (GPR109A).

256 ion channel protein and postphosphorylation allosteric modulation of the I(Ks) channel by Yotiao.

257 Allosteric modulation of the Kv11.1 channel efficiently

258 Allosteric modulation of the ligand-binding domain by ho

259 difficult to confer the high sensitivity for allosteric modulation of the M2 subtype onto the weakly

260 In addition to allosteric modulation of the maximum functional efficacy

261 50% binding efficiency, suggesting there is allosteric modulation of the melanocortin-4 receptor.

262 Negative allosteric modulation of the metabotropic glutamate 5 (m

263 molecular mechanism underlying the positive allosteric modulation of the MOP receptor by the Mg(2+)

264 olecular understanding of the activation and allosteric modulation of the MRGPRX1 receptor, which cou

265 Positive allosteric modulation of the mu-opioid receptor (MOPr),

266 isingly, Pepcan-12 exhibited potent negative allosteric modulation of the orthosteric agonist-induced

267 angements; and the molecular basis for PA200 allosteric modulation of the proteasome active sites.

268 Allosteric modulation of the receptor has recently emerg

269 ar determinants responsible for its positive allosteric modulation of the receptor, are unknown.

270 In complementary kinetic studies assessing allosteric modulation of the receptor, unlabeled THRX-16

271 Intriguingly, this allosteric modulation of the T3 channel is propagated th

272 ural insights into the mechanism of negative allosteric modulation of the uOR and demonstrate how thi

273 2 regulation, and suggest new routes for the allosteric modulation of their GTPase activity.

274 However, allosteric modulation of their scaffolding abilities and

275 harmacological strategies and models for the allosteric modulation of these ion channels.

276 the molecular basis for agonist binding and allosteric modulation of these proteins is poorly unders

277 Conversely, the negative allosteric modulation of tonic GABA conductance using L6

278 led TNF receptor (TNFR) function by inducing allosteric modulation of tryptophan-107 (W107) in the re

279 Ligand-biased signaling from, and allosteric modulation of, CB1Rs offer pharmacological ap

280 s to study the general mechanism of positive allosteric modulations of T1R taste receptors.

281 Thus, allosteric modulations of the cloned K(ATP) channel by A

282 , there is limited evidence of the impact of allosteric modulation on receptor regulatory mechanisms

283 o identify level and type (positive/negative allosteric modulation or full antagonism) of mGluR5 modu

284 nvestigated the effects of GABA(A)R positive allosteric modulation (PAM) by diazepam on brain activit

285 dentified a novel chemotype for the positive allosteric modulation (PAM) of the muscarinic acetylchol

286 inished 5-HT(2C)R signaling through positive allosteric modulation presents a novel therapeutic appro

287 ace of cells despite receptor activation and allosteric modulation properties that mirror a wild-type

288 Mutational studies suggest that allosteric modulation requires a direct interaction betw

289 incorporate concepts of allosteric agonism, allosteric modulation, signaling bias, constitutive acti

290 t on orthosteric agonist responses but block allosteric modulation (silent allosteric modulators (SAM

291 tion of beta-catenin via targeting a cryptic allosteric modulation site.

292 RGS proteins by regulation of expression or allosteric modulation to permit either increases or decr

293 -tubocurarine and may be subject to negative allosteric modulation to varying degrees by different pu

294 og DU124183 had the most favorable degree of allosteric modulation versus receptor antagonism.

295 Thus, astrocytes are required for positive allosteric modulation via the alpha3 subunit benzodiazep

296 sults will be discussed in terms of indirect allosteric modulations via amino acid substitutions and/

297 ar agonist probe dependence in the nature of allosteric modulation was apparent.

298 The observed allosteric modulation was consistent in all the function

299 f caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by

300 esults demonstrate functional selectivity of allosteric modulations within the D1R-D3R heteromer, whi