ライフサイエンスコーパス: lead compound

1 imal pharmacophore provided an indazole acid lead compound.

2 early 1980s as a promising antischistosomal lead compound.

3 biofilms, signifying the specificity of the lead compound.

4 oadmap to guide further optimization of this lead compound.

5 and in vivo tumor regression studies by this lead compound.

6 G profile relative to a previous frontrunner lead compound.

7 w micromolar range, making it an interesting lead compound.

8 h has characteristics of a suitable clinical lead compound.

9 gues 7, 12, and 17 were more potent than the lead compound.

10 and high selectivity toward P-gp, unlike the lead compound.

11 identified the fluoroethyl analogue 7b as a lead compound.

12 otein target or to drive improved potency of lead compounds.

13 R) follow-up of the saponification of oil by lead compounds.

14 important aspect in the design of potential lead compounds.

15 ehaviors often goes unexplored in pursuit of lead compounds.

16 quent successful optimization into drug-like lead compounds.

17 vements in the physicochemical properties of lead compounds.

18 e Topliss operational scheme to identify new lead compounds.

19 ress, selected antimalarial drugs, and novel lead compounds.

20 , azetidine, and cyclobutane to modify their lead compounds.

21 the xanthates, and the trithiocarbonates as lead compounds.

22 ceptor allosteric drugs with SB269652 as the leading compound.

23 Lead compound 1 (GNE-783), the prototype of the 1,7-diaz

24 ubstituents introduced to the indole ring of lead compound 1 (MI-136) to identify compounds suitable

25 ny previously reported RAD51 inhibitors, our lead compound 1 is capable of blocking RAD51-mediated D-

26 Modular optimization of lead compound 1 resulted in the discovery of benzoxazepi

27 We describe the structural optimization of a lead compound 1 that exhibits dual inhibitory activities

28 Optimization of lead compound 1, through extensive use of structure-base

29 difications of the known autotaxin inhibitor lead compound 1, to attenuate hERG inhibition, remove CY

30 lar effects of curcumin and the enone linker lead compound 1,7-bis(4-hydroxy-3-methoxyphenyl)hept-4-e

31 sesquiterpenes (2-82) by optimization of the lead compound 1.

32 s by presenting several modifications in the lead compounds 1 (HS665) and 2 (HS666).

33 Evaluation of lead compounds 1 and 2 (CHIR-611 or CT-98014) in rodent

34 nd based on its pharmacological profile, the lead compound 10a was evaluated in phase I metabolic sta

35 Binding of the lead compound 11 to the bromodomain of BRD9 results in a

36 alogues of 3 have identified an advanced new lead compound (11) displaying >20-fold higher affinity f

37 The lead compound 11l (GDC-0810 or ARN-810) demonstrates rob

38 FR from C. albicans and C. glabrata bound to lead compounds, 13 new para-linked compounds designed to

39 lodrug used in CC chemotherapeutics, and our leading compound 14Ru was shown to be significantly more

40 Lead compounds 17 (PF-4479745) and 18 (PF-4522654) displ

41 Lead compound 19 was selected based on its in vitro prof

42 R4 antagonist 13 was developed starting from lead compound 1a.

43 omal stability and CYP inhibition profile of lead compounds 1a and 1b led to the identification of 5

44 The lead compound 1o is fast acting and highly active agains

45 ld improvement in binding affinity, yielding lead compound 2 (KD = 15 muM).

46 Using our previously reported lead compound 2 (YK-4-279), we designed and synthesized

47 Selective hydrolysis of the C10 amide of lead compound 2 and subsequent derivatization led to nov

48 Lead compound 2 potently inhibits S1P-induced receptor i

49 lasma MPO activity was demonstrated with the lead compound 2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-th

50 One lead compound, 2-((2-(5-bromofuran-2-yl)-4-oxo-4H-chrome

51 The lead compound 21a exhibits reduced lipophilicity versus

52 -diamine derivatives led to development of a lead compound (-)-21a which exhibited very high affinity

53 The resulting lead compound 24 exhibited excellent enzyme inhibition a

54 This indicates that lead compound 29 displays selective activity against P.

55 structure-based design strategy resulted in lead compound 3 (DHBF-7-carboxamide; IC50 = 9.45 muM).

56 ons at the 2- and 5-indolyl positions on our lead compound 3-(5-methoxy-2-methyl-1H-indol-3-yl)-1-(4-

57 The lead compound 3-{4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetra

58 luster analysis of cytotoxicity data for the lead compound, 3, were identified as either poisons or i

59 (hGK-hGKRP IC50 = 1.2 muM) was optimized to lead compound 32 (AMG-0696; hGK-hGKRP IC50 = 0.0038 muM)

60 Lead compound 32 (UMB-32) binds BRD4 with a Kd of 550 nM

61 Lead compound 32 was shown to induce GK translocation fr

62 PK profiles and in vivo potency converged on lead compound 36 (JNJ-40411813).

63 hip (SAR) analysis, we obtained an optimized lead compound (38u) that represses breast cancer invasio

64 The lead compounds 3a and 3c inhibit HRAS expression, metabo

65 y chiral preparative HPLC, and the resulting lead compound (3R,5S)-31c showed promising efficacy in t

66 ptor affinity (K(i) = 60 nM) compared to the lead compound 4 (0.8 nM) but greatly enhanced solubility

67 Current lead compounds 4 and 5 exhibit on-target effects by spec

68 In addition, lead compounds 4 and 5 exhibited antibudding activity ag

69 While our initial lead, compound 4, was relatively potent and nontoxic, it

70 hiazole ring and pyrrolidine nitrogen of the lead compound 42 led to the identification of compound 5

71 The lead compound, 42a (MTC420), displays acceptable antitub

72 ring the course of our optimization program, lead compound 5 was deprioritized due to adverse finding

73 nterface as the quinoline-based ALLINIs, the lead compound, 5, inhibited IN mutants that confer resis

74 Lead compound 51 exhibited good in vitro potency and ADM

75 Oral administration of the lead compound 54 effectively induced a transient interfe

76 esized as bioisosteres of the 4'-nitrophenyl lead compounds 5a and 5g.

77 The lead compound, 6-(2-benzylphenyl)-3-phenyl-[1,2,4]triazo

78 The lead compounds, 6 and 12, exhibited strong activity in v

79 in vivo efficacy studies performed with the lead compound 65.

80 We demonstrate that our lead compound, [(68)Ga]-2, discriminates CA IX-expressin

81 d be driven and resulted in the discovery of lead compound 6b.

82 Lead compound 7 significantly decreased feeding in mice

83 Lead compounds 8, 9a, 18 and 19a are highly potent mitot

84 A lead compound (9b) showed high affinity for PSMA and the

85 minary mechanistic studies revealed that the lead compounds act through a mechanism distinct from tha

86 We document the antiviral properties of a lead compound against all 4 serotypes of DENV, antibody-

87 The selectivity of the lead compound against other bromodomain family members w

88 Past studies have focused on developing lead compounds against the ATP binding pockets of both D

89 The major challenge in designing lead compounds against the V-ATPase is its ubiquitous na

90 The lead compound also effectively reduced cariogenicity in

91 The lead compounds also proved to be very potent in the para

92 ciation assays, approximately half of the 38 lead compounds altered the radioligand dissociation rate

93 We tested a lead compound and derivatives for the ability to suppres

94 rystal structures of dCK in complex with the lead compound and with derivatives.

95 es and nucleic acids is critical to discover lead compounds and design novel aptamers.

96 To differentiate the lead compounds and enable prioritization for in vivo stu

97 vivo and in vivo cytokine production of the lead compound are presented.

98 X-ray crystallographic complexes of lead compounds are described and compared to a new compl

99 Our lead compounds are druglike, have low molecular weights,

100 Finally, we show that the lead compounds are orally efficacious in a 4 day murine

101 The lead compounds are promising as preclinical candidates f

102 Clearly, these lead compounds are strong candidates for development for

103 e the further development of these promising lead compounds as potential therapeutic agents to treat

104 Functional data confirms that our lead compound attenuates LPA mediated signaling in cells

105 ethyl groups, was established as the optimal lead compound because of its good in vitro potency and a

106 their normal cellular counterparts, with the lead compound being the bromo-benzophenanthridinone 968.

107 ivity issue, X-ray crystal structures of the lead compound bound to the CREB binding protein (CBP) an

108 ection experiments can provide not only many lead compounds but also insights into the structure-affi

109 The identification of lead compounds by these techniques is followed by the sc

110 The leading compound C-2h has been shown the most promising

111 a molecular docking screening and identify a lead compound, calcein, capable of blocking TopBP1 oligo

112 in addition, the lead compound can serve as a starting point for lead opt

113 Cell-based analysis indicated that the lead compounds can be effective in downregulating macrop

114 e known early in the screening workflow, and lead compounds can be rationally selected based on biolo

115 ivity of the most promising third-generation lead compound, CCG205432, and closely related analogs CC

116 Our optimized lead compound, CM-352 (2), inhibited fibrinolysis in hum

117 This lead compound completed a two week rat toxicology study,

118 Among these, one lead compound (compound 106) promotes Bax-dependent but

119 One of the lead compounds, compound 27 (DNS-8254), was identified a

120 One of the new promising lead compounds, compound 7, displayed nanomolar potency

121 An acyclic lead compound, containing an ether-linked isopropylsulfo

122 an SAR and, after several expansions, potent lead compounds could be obtained.

123 igned derivative of the previously described lead compound D3, which has been developed to efficientl

124 The lead compounds, data trends, and mechanistic insights re

125 teins to chemical degradation, and highlight lead compound dBRD9 as a tool for the study of BRD9.

126 This lead compound demonstrated robust Abeta42 reductions and

127 Both leading compounds demonstrated low cytotoxicity and exce

128 ty of pre-clinical studies, to better inform lead compound development and address the increasing att

129 oscopy showed that the Zn(II) complex of our lead compound, di-2-pyridylketone 4-cyclohexyl-4-methyl-

130 Additionally, the lead compound did not affect the overall growth of S. mu

131 Lead compounds discovered have potent and selective anti

132 tational methods to introduce X-bonding into lead compound discovery and optimization during drug dev

133 New drug targets and lead compounds exempt from cross-resistance with existin

134 In cancer cell lines, our lead compounds exhibit a dose-dependent decrease of phos

135 Lead compounds exhibited appreciable radical scavenging

136 Lead compounds exhibited low cellular toxicity and high

137 ty relationship (SAR) for this phenomenon, a lead compound FG03 with a hydroxyl group replacing the 3

138 The discovery of lead compound, FG03, is an example of reviving clinicall

139 ising PET tracer for brain tumor imaging and lead compound for a mixed system A and system L transpor

140 uch, the peptide described here may become a lead compound for a new class of positive inotropic agen

141 r, our data identify NSC59984 as a promising lead compound for anticancer therapy that acts by target

142 macological studies of Y4 receptors and as a lead compound for antiobesity drugs.

143 and mechanisms of action of a small molecule lead compound for cancer targeting.

144 class I selectivity, 7 could serve as a new lead compound for developing selective largazole analogu

145 findings identify isoeugenol as a potential lead compound for developing TDP2 inhibitors and encoura

146 These data support advancing BKI-1517 as a lead compound for drug development for cryptosporidiosis

147 of RyR1, to our knowledge, and represents a lead compound for further development of phosphatase-res

148 he selection of 25, HTL14242, as an advanced lead compound for further development.

149 in P. falciparum, and represents a promising lead compound for further drug development.

150 re tested in vitro and in vivo to identify a lead compound for further evaluation as novel oncolytic

151 inctive molecular mechanism, and a promising lead compound for further optimization toward the develo

152 ited the best profile and it was selected as lead compound for further studies.

153 nd suggest that diminazene is an interesting lead compound for high-affinity blockers of ASICs.

154 is a structural analog of histidine and is a lead compound for imaging cationic amino acid transport,

155 We believe that it could be a candidate or lead compound for new antithrombotic drug development.

156 erived nutraceutical, represents a promising lead compound for rational drug design and discovery.

157 e may have utility as a therapeutic agent or lead compound for skeletal muscle atrophy.

158 formation, aphidicolin becomes an attractive lead compound for the design of novel derivatives with e

159 findings suggest that LyP-1 could serve as a lead compound for the development of a new class of anti

160 Compound 18 represents a promising lead compound for the development of a new class of ther

161 hat benzofuroxan derivative 8 is a promising lead compound for the development of a novel chemical cl

162 signal modulation and could also serve as a lead compound for the development of D2 DAR-selective dr

163 Compound 3 is thus a promising advanced lead compound for the development of drugs for alleviati

164 As such, it represents a valuable lead compound for the development of drugs to treat neur

165 ate cancer cells and established WP1130 as a lead compound for the development of ERG-depleting drugs

166 vity inhibitor represents a highly promising lead compound for the development of novel anticancer th

167 tes and that piperine would provide a useful lead compound for the development of these therapies.

168 2.97 muM), thus being considered as a novel lead compound for the discovery of novel effective antit

169 In our study, curcumin was identified as a lead compound for the simultaneous inhibition of both ta

170 cacy of this screening strategy and identify lead compounds for anti-ZIKV drug development.

171 d 17.6 +/- 3.1 muM respectively, identifying lead compounds for anti-ZIKV drug development.

172 ailable, and only in the past 24 months have lead compounds for development as potential therapeutics

173 These results identify lead compounds for development of PKCepsilon inhibitors

174 s tools for studying channel function and as lead compounds for drug development.

175 effective means of identifying high-quality lead compounds for drug discovery programs.

176 inhibitory activity render them interesting lead compounds for further evaluation against atheroscle

177 nhibitor for GVIA iPLA2, which will serve as lead compounds for future development and studies.

178 These pyrazolopyrimidines can serve as lead compounds for future development of novel targeted

179 TP-binding inhibitors provide both tools and lead compounds for future drug development.

180 s that can be used as a tool-box to identify lead compounds for mIDH drug discovery programs, as well

181 ed phenolics from the Fabaceae are promising lead compounds for new antibacterials.

182 trials, the two compounds can also serve as lead compounds for optimization to speed the development

183 ach was followed to discover new targets and lead compounds for Parkinson's disease (PD) treatment.

184 Bacopasides could serve as novel lead compounds for pharmaceutic development of selective

185 id and tomatidine as potential agents and/or lead compounds for reducing ATF4 activity, weakness, and

186 nucleic acids that target GAA repeats can be lead compounds for restoring curative FXN levels.

187 specific small molecule ligands that provide lead compounds for subsequent optimization by fragment b

188 ,3]oxazine-2,4(3H)-diones could be potential lead compounds for the development of a new class of ant

189 pids here presented can be considered as new lead compounds for the development of drugs targeting TL

190 suggest that these compounds could serve as lead compounds for the development of improved diagnosti

191 These can serve as new lead compounds for the future development of CB1 alloste

192 em a notable interest for the development of lead compounds for the treatment of AD.

193 glutamate receptor A2 (GluA2) are promising lead compounds for the treatment of cognitive disorders,

194 urge in the development of PDE inhibitors as lead compounds for trypanocidal drugs.

195 tastasis and it identifies 2-O-Bn-InsP5 as a leading compound for development of anti-metastatic drug

196 The lead compound from series 4 also exhibited significant s

197 hidectomized rats, daily administration of a lead compound from this series showed anabolic activity

198 y also translates to M. tuberculosis, with a lead compound from this study potently suppressing carbe

199 optimize properties of previously described lead compounds from piperazinecarboxamide series.

200 However, our previous lead compound had a short half-life in vivo.

201 The lead compound had activity in cell-based assays and in a

202 This new lead compound has significantly improved metabolic stabi

203 he discovery of allosteric binding sites and lead compounds has been mostly serendipitous, achieved t

204 A detailed characterization of the lead compound highlighted the potential for treatment of

205 Torin 2, a top lead compound (IC50 = 8 nM against gametocytes in vitro)

206 is and the fungal specific property make the lead compounds ideal candidates for the development of n

207 The lead compound identified from the NCI-60 human tumor cel

208 he last 5 years by the discovery of many new lead compounds identified by phenotypic screening.

209 rs of influenza PA endonuclease derived from lead compounds identified from a metal-binding pharmacop

210 The lead compound (iKIX1) inhibits Pdr1-dependent gene activ

211 ew Ca(2+) channel agonist has potential as a lead compound in the development of new therapeutic appr

212 i6A and FPPS, pointing to i6A as a valuable lead compound in the search of new ligands endowed with

213 The lead compound in this class (5d) displays anti-inflammat

214 ine-3-sulfonamide (25) was identified as the lead compound in this series.

215 etermine the binding mode of tightly binding lead compounds in complex with difficult target proteins

216 or use in optimization of ADME parameters of lead compounds in drug discovery.

217 Many fungal isolates showed tolerance to lead compounds in growth inhibition assays and were able

218 f TRPV1 modulators that may become important lead compounds in the drug discovery process aimed at de

219 ed parasites suggests they have potential as lead compounds in the pursuit of novel drugs to treat ma

220 plifications of the scaffold to generate new lead compounds in the search for orally bioavailable cyc

221 The three lead compounds include the clinically approved drug, dig

222 Lead compounds increase dCTPase thermal and protease sta

223 tween dCK and the racemic mixture of our new lead compound indicated that the R-isomer is responsible

224 Preliminary studies revealed that lead compound inhibited human breast adenocarcinoma grow

225 , which led to identification of an improved lead compound (inS3-54A18) with increased specificity an

226 ration of design cycles required to optimize lead compounds into high-quality chemical probes or safe

227 A lead compound (known as VDR 4-1) demonstrated potent tra

228 of structural analogues led us to identify a lead compound (LQZ-7F), which was effective in blocking

229 lties associated with optimizing them into a lead compound makes them, in our opinion, poor scaffolds

230 cells suggests that 4 and possibly the other lead compounds may act independently of the p53 tumor su

231 Several of the lead compounds may prove of particular benefit as a nove

232 isplayed no or reduced ototoxicity, with the lead compound N1MS 17 times less ototoxic and with reduc

233 This screening workflow resulted in two lead compounds: NUCC-474 and NUCC-555.

234 The lead compounds obtained were found to (1) offer in vitro

235 HA15, the lead compound of this series, displayed anti-cancerous a

236 , which combine two units of artemisinin, as lead compounds of interest.

237 and enantiomer (R)-11 represent novel robust lead compounds of the IAS class.

238 , identifying the genome-wide off-targets of lead compounds or existing drugs will be critical for de

239 le manner, may provide potential therapeutic lead compounds or molecular probes to study p300/HIF-1al

240 The resulting lead compound, Pam-(Lys-betaNSpe)6-NH2, blocks LPS-induc

241 The resultant lead compounds possess potent activity against a multidr

242 ed by robust secondary assays that establish lead compound potencies and provide further insights int

243 systemic inhibition of KMO in vivo with this lead compound provides pharmacodynamic evidence for modu

244 The leading compounds represent viable preclinical candidate

245 trong and selective binders from promiscuous lead compounds represents one of the most expensive and

246 A critical goal of lead compound selection and optimization is to maximize

247 ific structural changes at key points of our lead compound SG2 skeleton.

248 The selected lead compound showed excellent in vitro and in vivo acti

249 An early lead compound showed robust Abeta lowering activity in a

250 Lead compounds showed inhibition of the HCV pseudopartic

251 Further evaluation of the lead compounds showed that in vivo genotoxic degradants

252 e-based rational drug design, and identify a lead compound, SP-141, which can directly bind to MDM2,

253 AML together with the success in developing lead compounds specific to key histone methylation-modif

254 Lead compounds such as 63 exhibit low nM inhibition of b

255 The lead compound surotomycin exhibited significantly improv

256 gn principles to provide chemical probes and lead compounds targeting structured RNAs.

257 ivation and signaling, therefore new hit and lead compounds targeting this receptor activation proces

258 These findings identify a new lead compound that attenuates HIV replication by liberat

259 We identified R10015 as a lead compound that blocks LIMK activity by binding to th

260 hat this novel small molecule inhibitor is a lead compound that can be further optimized for cancer t

261 oid receptor (DOR) antagonist ligands with a lead compound that produced antinociception for 1 h afte

262 ridin-1-yl)(4-methoxyphenyl)methanone (CL6a) lead compound that showed a reversible mechanism of MAGL

263 has been proposed and the development of new lead compounds that could target the CSE enzyme.

264 al screening data, was optimized to generate lead compounds that possess potent antimalarial activity

265 ch to identify systematically small molecule lead compounds, thus offering an appealing opportunity t

266 This opens the possibility of using EGA as a lead compound to develop novel inhibitors of botulinum n

267 se results suggest that LOC14 is a promising lead compound to evaluate the potential therapeutic effe

268 phagy-oriented clinical trials and promising lead compounds to modulate autophagy for therapeutic ben

269 bility, prodigiosin and its analogue provide lead compounds to rescue deficiencies in the p53 pathway

270 We identified a lead compound, UM101, that was at least as effective as

271 This lead compound was characterized by low dark toxicity (TC

272 Function of one such lead compound was confirmed by its activity in suppressi

273 In our study, a kinase lead compound was fragmented, the hinge-binding motif ex

274 The resulting lead compound was highly potent, selective, and achieved

275 A library based on the most active lead compound was made accessible by esterification of t

276 be how a noncovalent double mutant selective lead compound was optimized using a strategy focused on

277 The lead compound was then evaluated in vivo for antiangioge

278 oreover, robust target engagement of LDHA by lead compounds was demonstrated using the cellular therm

279 Our selected lead compounds were able to expand functional HSCs in a

280 Lead compounds were confirmed as RAD52 inhibitors in bio

281 library were inactive when tested alone, but lead compounds were identified using Zn(2+) as an allost

282 r anticancer activity, and several cytotoxic lead compounds were identified.

283 Slower dissociation rates (koff) of the lead compounds were observed as the program progressed.

284 This work resulted in a promising lead compound which exhibits tight and selective binding

285 ment hit resulted in the identification of a lead compound which reduced paw swelling in a dose- and

286 n as informed by docking studies, granting a lead compound with a submicromolar Ki.

287 that led to the identification of a program lead compound with a suitable ADME/PK profile for therap

288 ultimately resulted in the development of a lead compound with an IC50 value of 14 nM, which display

289 identification of pyridin-2(1H)-one 18b as a lead compound with good potency (IC50 = 1.6 nM) and sele

290 1a (KB2115), a thyroid hormone analog, as a lead compound with low micromolar potency.

291 on provided a 4-phenyl-3-aryl-sulfoquinoline lead compound with the minimal pharmacophore.

292 2 secretion, a novel approach that may yield lead compounds with a high potential to develop into ant

293 Thus, lead compounds with a high selectivity toward killing of

294 ifying bacterial sliding clamp inhibitors as lead compounds with broad-spectrum antibacterial activit

295 ese efforts led to the identification of two lead compounds with excellent antiviral activity and pre

296 In addition, they are valuable lead compounds with great potential for drug development

297 he identified drugs represent a new class of lead compounds with piperidine, benzothiophene, and indo

298 However, development of druglike lead compounds with selectivity for the D3 receptor has

299 T cells at an EC50 of 36 mum The identified lead compound, with a relatively small molecular weight

300 nd address the increasing attrition rates of lead compounds within the pharmaceutical industry, which