ライフサイエンスコーパス: inactivator

1 arginine carboxypeptidase, and anaphylotoxin inactivator).

2 acquired at least one (2)H from the labeled inactivator.

3 conclusion that furafylline is an efficient inactivator.

4 a consequence of the effects of a cytosolic inactivator.

5 activation of 0.1 microM MAO-B by 500 microM inactivator.

6 ting neutrophils is regulated by a cytosolic inactivator.

7 substantially reduced levels of this PTPase inactivator.

8 e or mixed competitive-noncompetitive CYP3A4 inactivator.

9 sually only recognizes one enantiomer of the inactivator.

10 finity but does not act as a mechanism-based inactivator.

11 that the ( R) enantiomer is the more potent inactivator.

12 anisms based on the binding direction of the inactivator.

13 acid (12) was designed as a mechanism-based inactivator.

14 agenesis and subsequent exposure to affinity inactivators.

15 ct readily with prototypical serine protease inactivators.

16 cy and selectivity of (acyloxy)methyl ketone inactivators.

17 plication as, for example, targeted protease inactivators.

18 er than as suicide substrates or active site inactivators.

19 ing that these compounds are mechanism-based inactivators.

20 a benefit to 4-substitution in this class of inactivators.

21 th a series of N-cyclopropyl mechanism based inactivators.

22 ore classified as active-site-directed redox inactivators.

23 which is typical for mechanism-based enzyme inactivators.

24 st potent and broad spectrum mechanism-based inactivators.

25 amine, and hydrazine-functionalities as LSD1 inactivators.

26 and characterization the two most potent AgD inactivators.

27 10-1000-fold over previously reported PAI-1 inactivators.

28 me P-450 ligands such as the mechanism-based inactivator 1-aminobenzotriazole did not inhibit iNOS.

29 13-acetate (500 nM), and blocked by the PKC inactivator (+/-)-1-(5-isoquinolinesulfonyl)-2-methylpip

30 dy has led to the identification of a potent inactivator (10) for this enzyme, and study of its inact

31 blished CYP3A4 substrate and mechanism-based inactivator, 17-alpha-ethynylestradiol (17EE), via click

32 We evaluated a novel GABA-AT inactivator (1S, 3S)-3-amino-4-difluoromethylenyl-1-cycl

33 the negatively charged (at physiological pH) inactivators 2-amino-O4-benzylpteridine-6-carboxylic aci

34 ve covalent modification of COX-2 by a novel inactivator, 2-acetoxyphenyl hept-2-ynyl sulfide (70).

35 e incorporation of two (13)C labels into the inactivator, [2,3-(13)C(2)]-1-PCPA, followed by analysis

36 The first reported mechanism-based inactivator, 3-decynoyl-N-acetylcysteamine (3-decynoyl-N

37 ally rigid analogues (7-15) of other GABA-AT inactivators, 4-amino-5-halopentanoic acids, were synthe

38 A new bicyclomycin irreversible inactivator, 5a-formylbicyclomycin (3), was prepared to

39 Autoinducer inactivator A (AiiA) is a metal-dependent N-acyl homoser

40 identification of CAPRI (Ca(2+)-promoted Ras inactivator), a Ca(2+)-dependent Ras GTPase-activating p

41 means to explore the structure of the flavin-inactivator adduct of MAO N.

42 ther structural identification of the flavin-inactivator adduct.

43 n leads to covalent attachment of 2 equiv of inactivator after gel filtration; upon urea denaturation

44 ion in vitro and test the design of specific inactivators aimed at blocking the production of the pyr

45 them, (+)-7, (-)-9, (+)-10, and (+)-15, were inactivators, although not as potent as the correspondin

46 sma amine oxidase (BPAO) both as a temporary inactivator and as a substrate.

47 del does not show an interaction between the inactivator and Asp66.

48 igned a pantetheine-like chloromethyl ketone inactivator and co-crystallized it with ThnT.

49 ed complex elucidates the orientation of the inactivator and its covalent attachment to the active si

50 thiols to form a mixed disulfide between the inactivator and papain.

51 ons of analogs of ritonavir, a potent CYP3A4 inactivator and pharmacoenhancer, we have built a pharma

52 is direct transfer of hydrogens between the inactivator and the 5'-methyl of 5'-deoxyadenosine.

53 ass of highly water-soluble alkyltransferase inactivators and form the basis to construct more tumor-

54 have been achieved by use of mechanism-based inactivators and photoaffinity ligands.

55 s of the mycotoxin cerulenin (a covalent FAS inactivator), and the novel small compound C75 (a slow-b

56 tanedione and phenylglyoxal were found to be inactivators, and inactivation could be protected agains

57 ify and characterize drug candidates as P450 inactivators are important in drug discovery and develop

58 Affinity inactivators are useful for probing catalytic mechanisms

59 e for further design of peptidomimetic HIV-1 inactivators based on the PT pharmacophore.

60 Thus, these inactivators behave as unique suicide substrates.

61 or BH3-only molecules function downstream of inactivator BH3-only molecules to activate BAX-BAK.

62 differentially inactivated by the remaining 'inactivator' BH3-only molecules including BAD, NOXA, BMF

63 Molecular modeling is used to investigate inactivator binding, reaction, and also a final pyridini

64 Pretreatment of HMG-CoA synthase with the inactivator blocks the enzyme's ability to form Michaeli

65 th models of the enzymes with the acetylenic inactivator bound in the active site suggest that the T3

66 cyclohex-3-ene-1-carboxylic acid (6) are not inactivators but are competitive reversible inhibitors o

67 ated with sodium tungstate (xanthine oxidase inactivator); c) an aorta occlusion group; and d) an aor

68 ated with sodium tungstate (xanthine oxidase inactivator); c) aorta occlusion group; and d) aorta occ

69 d by the recruitment of calcium-promoted Ras inactivator (CAPRI), a GTPase-activating protein, to the

70 Here we show that the calcium-promoted Ras inactivator (CAPRI), a Ras GTPase-activating protein, fu

71 ential susceptibility to the mechanism-based inactivators chloramphenicol and N-(2-p-nitrophenethyl)c

72 l- and O(6)-cycloalkylguanines were weak AGT inactivators compared with O(6)-allylguanine (IC(50) = 8

73 nd inactivation rate constant at an infinite inactivator concentration are 0.87 microM and 0.039 minu

74 nd inactivation rate constant at an infinite inactivator concentration are 2.19 microM and 0.0056 min

75 For the inactivation of CYP3A4, the inactivator concentration at the half-maximum rate of in

76 For CYP3A5 inactivation, the inactivator concentration at the half-maximum rate of in

77 enzylguanine, the prototype alkyltransferase inactivator currently in clinical trials.

78 ages, we pretreated mice with the macrophage inactivators/depeleters gadolinium chloride (7 mg/kg, in

79 only the expected decrease by the macrophage inactivators/depleters, but also an apparent increase in

80 O6-(4-bromothenyl)guanine is the most potent inactivator described to date with an IC50 of 0.1 nM.

81 The PAD4 inactivators described herein will be useful pharmacolog

82 The R244S mutation affects beta-lactamase inactivators differently, but resistance can be overcome

83 th ventricle pretreatment with the astrocyte inactivator fluorocitrate.

84 acetylene (tBPA) is a potent mechanism-based inactivator for cytochrome P450 2B4 (P450 2B4) in the re

85 xplored as a heme ligand and mechanism-based inactivator for the design of cytochrome P450 inhibitors

86 mples of fully characterized mechanism-based inactivators for an aspartyl protease and show promise a

87 similar strategy may provide highly specific inactivators for other protein kinases as well.

88 uation are novel SERMs, aromatase inhibitors/inactivators, gonadotrophin-releasing hormone agonists,

89 otide exchange factors; GEFs) and Rho GTPase inactivators (GTPase-activating proteins; GAPs), we find

90 We have used two mechanism-based inactivators, guanabenz and NG-amino-L-arginine, to alte

91 Recombinant expression of the TAP inactivator ICP47 by adenoviral-mediated transduction wa

92 OP, a metal chelator and p53 inactivator in cell free systems, however, induces p53 t

93 w approach for the design of mechanism-based inactivators in general.

94 The inactivator is particularly effective at pH 9.0, with a

95 ble mechanism for inactivation by one of the inactivators is proposed.

96 The value of k(inact)/K(i) for these inactivators is strongly dependent on the leaving group.

97 igabatrin, a GABA aminotransferase (GABA-AT) inactivator, is used to treat infantile spasms and refra

98 e 4-carbon acid is the best substrate-analog inactivator known to date for PDHc, more potent than eit

99 ost potent irreversible, mechanism-based PHM inactivator known.

100 and psoralen (P)] tested as mechanism-based inactivators (MBIs) of purified reconstituted cytochrome

101 prior intranigral injection of the receptor inactivator N-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinol

102 iously unknown class of potential PLP enzyme inactivators; namely, a family of quaternary, alpha-(1'-

103 on, indicating that GDP-2F-Fuc is neither an inactivator nor a slow substrate.

104 result of the liberation of the more potent inactivators, O(6)-benzylguanine and O(6)-benzyl-2'-deox

105 (S)-Epoxypropane was an inactivator of (R)-epoxypropane carboxylation by compone

106 onents I- III, while (R)-epoxypropane was an inactivator of (S)-epoxypropane carboxylation by compone

107 Finasteride is a mechanism-based inactivator of 5alpha-reductase type 2 with subnanomolar

108 lcholinesterase (AChE), the primary synaptic inactivator of acetylcholine.

109 DEA has been believed to be an inactivator of AdoHcyase, but this study indicates that

110 O6-Benzylguanine (BG) is a potent inactivator of AGT, resulting in an increase in the sens

111 tibacterial activity and is a time-dependent inactivator of all purified Gram-positive bacterial alan

112 amino-L-arginine (NAA) is a metabolism-based inactivator of all three major nitric-oxide synthase (NO

113 kinase phosphatase that functions as both an inactivator of and a nuclear anchor for ERK2 in mammalia

114 ted earlier as a potent active site-directed inactivator of bovine liver enoyl-CoA hydratase (ECH).

115 me- and concentration-dependent irreversible inactivator of bovine plasma amine oxidase (BPAO), exhib

116 , 4) and was found to be an even more potent inactivator of BPAO than 1, exhibiting a 5 min IC(50) of

117 Its role as an inactivator of C3b and C4b deposited on self-tissue is h

118 from binding to Trp3, and calmidazolium, an inactivator of Ca(2+)/CaM.

119 irus p35 protein, the broad spectrum suicide inactivator of caspases.

120 a potent peroxidase-mediated mechanism-based inactivator of COX-1 only (k(inact) = 0.069 +/- 0.004 s(

121 B) is a relatively selective mechanism-based inactivator of cytochrome P450 2B1, that partitions betw

122 the quad pill includes cobicistat (COBI; an inactivator of cytochrome P450 isoenzyme CYP3A without a

123 t-Butyl acetylene (tBA) is a mechanism-based inactivator of cytochromes P450 2E1 and 2E1 T303A; howev

124 e data suggest that caspase-3 is the primary inactivator of DFF45/ICAD and therefore the primary acti

125 Eniluracil (776C85) is an effective inactivator of dihydropyrimidine dehydrogenase that allo

126 Eniluracil (776C85), a potent inactivator of dihydropyrimidine dehydrogenase, allows f

127 ne arm of a paired study with eniluracil, an inactivator of dihydropyrimidine dehydrogenase, enabling

128 Eniluracil is being developed as an inactivator of dihydropyrimidine dehydrogenase, the enzy

129 ations revealed that BES is a time-dependent inactivator of dithiothreitol-reduced 2-KPCC, where the

130 racterized as a time-dependent, irreversible inactivator of epoxide carboxylase activity that is prop

131 lepoxypropane, a time-dependent irreversible inactivator of epoxide carboxylase activity, suggesting

132 s found to be a time-dependent, irreversible inactivator of epoxyalkane-degrading activity.

133 (IP-dUMP) is a mechanism-based, irreversible inactivator of Escherichia coli thymidylate synthase (TS

134 These data suggest that plasmin is a potent inactivator of factor Va and that region 307-348 of the

135 ter potency than that of vigabatrin, a known inactivator of GABA-AT and approved drug (Sabril) for th

136 d in the series is 8 times more efficient an inactivator of GABA-AT than vigabatrin, the only FDA-app

137 BA-AT than vigabatrin, the only FDA-approved inactivator of GABA-AT.

138 K, and AKT are inhibited by pertussis toxin (inactivator of Gi proteins) and by DPCPX (A1-selective a

139 hate is an active site-directed irreversible inactivator of GlmS from Escherichia coli (kinact/KI = 1

140 n isozyme-selective and active site-directed inactivator of glutathione S-transferase (GST).

141 O6-Benzylguanine (BG) is a potent inactivator of human AGT (ED50 of 0.1 microM) that is cu

142 entration-, and NADPH-dependent irreversible inactivator of iNOS.

143 that citral is an effective mechanism-based inactivator of isozyme 2B4, with a KI of 44 microM as de

144 f benzene-dependent O2 consumption and as an inactivator of ISPNAP.

145 y bioavailable, mechanism-based irreversible inactivator of LSD1.

146 een to act as a time-dependent, irreversible inactivator of lysine decarboxylase from Hafnia alvei.

147 Dusp1 is an inactivator of mitogen-activated protein kinase (MAPK),

148 opyl)glycine (CPG) acts as a mechanism-based inactivator of MSOX.

149 yl-d-isocitrate (2-VIC) as a mechanism-based inactivator of Mtb ICL1 and ICL2.

150 structs expressing the temperature-sensitive inactivator of neuronal function Shibire(ts1), and for t

151 Guanabenz, a metabolism-based irreversible inactivator of neuronal nitric-oxide synthase (nNOS) in

152 O(6)-Benzylguanine is an irreversible inactivator of O(6)-alkylguanine-DNA alkyltransferase cu

153 ha-difluoromethylornithine (DFMO), a suicide inactivator of ODC, in the drinking water from birth, th

154 inction of a class of compounds acting as an inactivator of one amine oxidase family and a pure subst

155 dine, a potent and bioavailable irreversible inactivator of PAD4.

156 ructural characterization of a high affinity inactivator of PAI-1.

157 For example, Z-Phe-Gly-CH(2)-X is a poor inactivator of papain when X is OCOCH(3) (k(inact)/K(i)

158 rt the first metabolism-dependent, selective inactivator of PGHS-2.

159 As a mechanism-based inactivator of PLP-enzymes, (S)-4-amino-4,5-dihydro-2-th

160 carbonitrile was found to be an irreversible inactivator of PncA, with a kinact/KI of 975 M(-1) s(-1)

161 ridium difficile toxin B (CdTxB), a specific inactivator of Rho-GTPases, significantly blocked KSHV e

162 lostridium botulinum C3 exotoxin, a specific inactivator of RhoA family members.

163 ablishes that F(2)CDP is a substoichiometric inactivator of RNR.

164 Importantly, treatment with an inactivator of ROS reversed the T-cell suppressive funct

165 toxin 3-nitropropionic acid, an irreversible inactivator of succinate dehydrogenase, forms a covalent

166 ransferase (NAT) was first identified as the inactivator of the anti-tubercular drug isoniazid.

167 O6-Benzylguanine is a potent inactivator of the DNA-repair protein, O6-alkylguanine-D

168 lic acid was identified as a mechanism-based inactivator of the enzyme [K(i) = 38.1 +/- 6.0 microM an

169 VG is both a substrate and a mechanism-based inactivator of the enzyme, but the partition ratio, k(ca

170 ity that is proposed to be a mechanism-based inactivator of the enzyme.

171 lcyclopropylamine (1-PCPA) is shown to be an inactivator of the fungal flavoenzyme monoamine oxidase

172 elimination reactions, is not a significant inactivator of the medium-chain dehydrogenase.

173 and synthesis of a potential mechanism-based inactivator of the protein.

174 -vinylGABA) is known to be a mechanism-based inactivator of the pyridoxal phosphate (PLP)-dependent e

175 activity of the Arg substrate p190RhoGAP, an inactivator of the RhoA GTPase.

176 at aminoguanidine (AG) is a metabolism-based inactivator of the three major isoforms of nitric-oxide

177 inhibitors, neuroserpin is a more effective inactivator of tPA than of urokinase-type plasminogen ac

178 MTS-galactose derivatives behave as affinity inactivators of a functional mutant with Ala(122)-->Cys

179 s containing a central b(6)G are more potent inactivators of AGT than b(6)G.

180 Drug Administration-approved small molecule inactivators of any serpins.

181 beta-PAD and 6 beta-PED are mechanism-based inactivators of aromatase.

182 The covalent 2'-deoxynucleoside inactivators of CD38 are powerful inhibitors by acting a

183 retinylamine analogs as active-site directed inactivators of constitutively active mutants of rhodops

184 se (GABA-AT) inactivator vigabatrin were not inactivators of GABA-AT.

185 ntanoic acids, were synthesized as potential inactivators of GABA-AT.

186 vigabatrin and as potential mechanism-based inactivators of gamma-aminobutyric acid aminotransferase

187 Env gp120 encounter by peptide triazole (PT) inactivators of HIV-1.

188 d mechanism is proposed in which the amidine inactivators of iNOS bind as does substrate L-arginine,

189 oic acid, were NADPH-dependent, irreversible inactivators of iNOS.

190 ed from indoline resulted as the most potent inactivators of lipoxygenase, with IC50 values of 41.4 a

191 clopropylamines can serve as mechanism-based inactivators of LSD1.

192 and shown to be time-dependent, irreversible inactivators of monoamine oxidase B (MAO B).

193 30A mutant were inactivated with three known inactivators of monoamine oxidase, namely, phenylhydrazi

194 own for the first time that the irreversible inactivators of nNOS, perhaps through covalent alteratio

195 H and were more than 200-fold less active as inactivators of O(6)-alkylguanine-DNA alkyltransferase (

196 he study of small molecules as inhibitors or inactivators of OAT or as a method to determine OAT acti

197 ribed here could be applied to the design of inactivators of other heme-dependent enzymes.

198 We have synthesized (acyloxy)methyl ketone inactivators of papain, cathepsin B, and interleukin-1be

199 g N-alkylmaleimides were only time-dependent inactivators of PGHS, suggesting that the carboxylate is

200 probes are active site-directed irreversible inactivators of PTPs and form a covalent adduct with PTP

201 pyrones which are nonselective, irreversible inactivators of serine hydrolases.

202 a-lactams, and N-acyl beta-sultams are novel inactivators of the class C beta-lactamase of Enterobact

203 (7) are shown to be as potent or more potent inactivators of the human DNA repair protein O6-alkylgua

204 as competitive inhibitors and as mechanistic inactivators of the inducible isoform of NOS (iNOS).

205 inactivated by 17EE or efavirenz, which are inactivators of the wild-type enzyme.

206 ne 5'-diphosphate (FMCDP) are time dependent inactivators of this protein, with approximately 1.5 equ

207 tion of mTORC1 signaling, demonstrating that inactivators of TR3 represent a novel class of mTORC1 in

208 reviously reported to be inhibitors, but not inactivators, of GABA-AT.

209 nism, makes the design of new beta-lactamase inactivators or beta-lactamase-stable beta-lactams all t

210 se of raloxifene, any aromatase inhibitor or inactivator, or fenretinide to lower the risk of develop

211 These novel inactivators owe their potency to an S-farnesylcysteine

212 s the enzyme from inhibition by the covalent inactivator p-fluorosulfonylbenzoyl 5'-adenosine at 0.5

213 this protocol can be easily adapted to other inactivators, P450 isoforms, substrates and plate reader

214 ex formation between the PKC isozyme and the inactivator peptide.

215 lts provide evidence that the N-biotinylated inactivator peptides are active-site affinity labels of

216 The inactivator peptides most likely function by S-thiolatin

217 r intranigral injection of the Gi-Go-protein inactivator pertussis toxin (1 mg/ml 0.9% NaCl 24 h befo

218 ctors which contribute to their substrate vs inactivator properties.

219 in cell-free extracts by the mechanism-based inactivator propyne, suggesting that it is the catalytic

220 s unusual selectivity toward mechanism-based inactivators provides additional discrimination between

221 activator (PI3-kinase) and a globally acting inactivator (PTEN or a similar phosphatase) are coordina

222 We conclude that these inactivator reactions mainly involve motion of the pseud

223 NPS-2143 are allosteric CaSR activators and inactivators, respectively, that ameliorate signaling di

224 between the action of the activator and the inactivator results in a spatially oriented persistent s

225 and EP4, Akt, small GTPase RalA and Ral.GTP inactivator RGC2.

226 constitute a new category of mechanism-based inactivators selective for lysyl oxidase.

227 e if this is a general phenomenon of GABA-AT inactivators, several mono- and di-halogen-substituted c

228 ll known affinity labels and mechanism-based inactivators should allow the procurement of a wide rang

229 Titrations with the phosphorylase inactivator showed that stimulation of glycogen synthesi

230 Mechanism-based inactivators such as bergamottin are useful chemical too

231 us structure of LacY with a covalently bound inactivator suggests that the galactopyranoside must be

232 ptible" to inhibition by the mechanism-based inactivators tazobactam, sulbactam, and clavulanic acid.

233 2B4 covalently bound to the mechanism-based inactivator tert-butylphenylacetylene (tBPA) has yielded

234 yguanosine were more potent alkyltransferase inactivators than the parent nucleoside.

235 alues, and primary aldehydes are more potent inactivators than the structurally related secondary and

236 The 4-substituted analogues were more potent inactivators than the unsubstituted analogue, indicating

237 ein phosphatase 5 (PP5) was identified as an inactivator that associates with Raf-1 on growth factor

238 esents the first example of an peptide-based inactivator that fully distinguishes between these two c

239 se data reveal that p35 is a mechanism-based inactivator that has adopted an inhibitory device remini

240 t adduct between enzyme and a portion of the inactivator that includes the CoA nucleotide.

241 ) is a potent inhibitor and reversible redox inactivator that reacts with MCRred1 to form an EPR-acti

242 ion mechanism for CPP-115, a mechanism-based inactivator that undergoes GABA-AT-catalyzed hydrolysis

243 1 exists that is vulnerable to inhibition by inactivators that bind at the vitronectin binding site.

244 ormational constraint has a larger effect on inactivators that inactivate by a Michael addition mecha

245 Experiments with two mechanism-based inactivators that target the FAD of the medium- and shor

246 rs a basis for the design of selective COX-1 inactivators that work through a mechanism-based event a

247 analysis of a carbocyclic mechanism-based GH inactivator, the results of which show that the two Mich

248 As a result of inhibition of the cytosolic inactivator, the translocated PTPase expresses full acti

249 nd in contrast to previously described PAI-1 inactivators, these compounds inactivate PAI-1 in the pr

250 tization and sensitivities to activators and inactivators; they can also have different intracellular

251 e supports covalent attachment of the 1-PCPA inactivator to the cofactor as N(5)-3-oxo-3-phenylpropyl

252 earrangement that leads to attachment of the inactivator to the PLP, which is bound to the protein (S

253 difications include the addition of an RNase inactivator to the reaction mixture, elimination of a si

254 Other metabolism-based irreversible inactivators to nNOS, N(G)-methyl-L-arginine, and N(5)-(

255 ogues of the GABA aminotransferase (GABA-AT) inactivator vigabatrin were not inactivators of GABA-AT.

256 nvestigating cytochrome P450 mechanism-based inactivators; we use the example of CYP2B6 and bergamott

257 inhibitors although several mechanism-based inactivators were identified.

258 = 2.5 M(-)(1) s(-)(1)) but becomes a potent inactivator when X is OCO-L-Leu-Z (k(inact)/K(i) = 11 00

259 hat chlorovinyl-H3 is a mechanism-based LSD1 inactivator whereas endo-cyclopropylamine-H3 does not sh

260 esidue stabilizes the pyridinium form of the inactivator, which has enhanced reactivity toward the ac

261 veral reversible inhibitors and irreversible inactivators, which have been used to implicate one or m

262 thyl)-L-ornithine amide (Cl-amidine), a PAD4 inactivator with enhanced potency.

263 sly identified mechanism-based, irreversible inactivator with moderate nNOS selectivity.

264 s enantiomers are relatively modest covalent inactivators with kobs/[I] = 46 M-1 s-1 for the R enanti

265 nitrosylation in the incubation of S-nitroso inactivators with papain was excluded.

266 A series of inactivators with the general structure Fmoc-L-Asp-CH(2)

267 ), octenoyl-CoA (product), and octynoyl-CoA (inactivator) with medium chain acyl-CoA dehydrogenase (M

268 loalkenylguanines proved to be excellent AGT inactivators, with 1-cyclobutenylmethylguanine (IC(50) =

269 her modest residence time or a contaminating inactivator within an inhibitor sample, in either case p