ライフサイエンスコーパス: lead compound

1 , and has enabled identification of a potent lead compound.

2 ize the binding mode of the newly identified lead compound.

3 (MC70), modifying the phenolic group of the lead compound.

4 biofilms, signifying the specificity of the lead compound.

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

6 h has characteristics of a suitable clinical lead compound.

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

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

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

10 imal pharmacophore provided an indazole acid lead compound.

11 how these linkers are designed to obtain the lead compound.

12 nd provides an attractive probe molecule and lead compound.

13 viral therapy we re-identified amicetin as a lead compound.

14 vation of RXR, MSU-42011 was selected as our lead compound.

15 domain of TDP1 was conducted to identify new lead compounds.

16 enantiopure R- and S-enantiomers of the four lead compounds.

17 analogues was screened to identify potential lead compounds.

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

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

20 the xanthates, and the trithiocarbonates as lead compounds.

21 ace, accelerating the discovery of selective lead compounds.

22 ceptor allosteric drugs with SB269652 as the leading compound.

23 Optimization of our lead compound 1 (( Z)-2-benzylidene-3-oxo-2,3-dihydroben

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 template and trans-cyclobutyl linker of the lead compound 1 were left unchanged, while side-group Ea

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

28 derivatives were less potent inhibitors than lead compound 1, whereas steroidal backbone (A-ring) cha

29 yed higher plasma concentration in mice than lead compound 1.

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

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

32 opy, which permits the use of low amounts of lead compounds (1-5 mumol).

33 identification and preclinical profile of a lead compound 10, (SPR519) as an equally potent dual inh

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

35 h a stable nanosuspension was identified for lead compound 12.

36 cessive optimization led to the discovery of lead compound 15a.

37 The most potent lead, compound 16, exhibited low nM to low muM inhibitio

38 However, the lead compound 1a suffered from enterohepatic circulation

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

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

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

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

43 In a mouse PK/PD model, oral dosing of lead compound 2 demonstrated dose-dependent inhibition o

44 nding model led to the identification of the lead compound 2-hydroxy-4-((4-(naphthalen-2-yl)thiazol-2

45 re-activity relationship studies resulted in lead compounds 23 and 36 that simultaneously inhibited P

46 The resulting lead compound 24 exhibited excellent enzyme inhibition a

47 The lead compound, 28 (BPN14770), has entered midstage, huma

48 biphenyl triazoles among which stands out a lead compound, 34, that is endowed with an inhibitory ac

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

50 n of the series led to identification of the lead compound 3a that displayed excellent potency, selec

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

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

53 Lead compound 46 originating from the FEP calculations s

54 The lead compound 48c, induced necrosis in several mutant an

55 We extensively characterize a lead compound (4a), which potently inhibits clinically d

56 s work led to the identification of a potent lead compound (4aa, NEU-4854) with improved in vitro abs

57 Lead compound 4b (BSc5371) displays superior cytotoxicit

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

59 resolution of the chiral centers resulted in lead compound 53 and eutomer 53a that demonstrate signif

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

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

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

63 Optimization of 2 gave lead compound 6a (2-methyl-7-nitrothieno[3,2-d]pyrimidin

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

65 and in vivo toxicology findings of an early lead compound 7 with a human dose predicted to be 30 mg

66 eothin-derivatives successfully identified a lead compound (#7) superior to Aureothin that combines s

67 The lead compound 7h which is active against HCT116 and SW62

68 The ester group in the lead compound 8i was modified to incorporate amino-amide

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

70 Remarkably, our lead compound achieved a 10-fold increase in receptor af

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

72 drug discovery efforts focus on identifying lead compounds acting on a molecular target associated w

73 The new lead compounds activate selectively the alpha7 nAChRs wi

74 inol-containing molecule, PIPD1, as a potent lead compound against M. tuberculosis Herein, we show th

75 The lead compound also effectively reduced cariogenicity in

76 ng from 1 to 32 nM), higher than that of the lead compound and reference drug.

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

78 ynthesis, and evaluation of fragments of the lead compounds and property-focused optimization.

79 Two lead compounds are discovered, YLL3 and YLL8, both of wh

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

81 p studies and rat pharmacokinetic studies of lead compounds are presented.

82 The lead compounds are promising as preclinical candidates f

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

84 The lead compound, AS15, is a covalent nanomolar inhibitor o

85 he molecular mechanism of interaction of the lead compound ATM-3507 with Tpm3.1-containing actin fila

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

87 ely employed in the rational modification of lead compounds, being used to increase potency, enhance

88 The lead compound blocked VISTA signaling in vitro, enhanced

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

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

91 Small structure modifications to hit or lead compounds can have meaningful impacts on pharmacolo

92 The activity of our lead compound, CM-272, was examined in HCC cells under n

93 luation of analogues, we have discovered two lead compounds, CMLD012043 and CMLD012044, which show pr

94 We identified a potent lead compound [compound 14 (ARN-21934) IC(50) = 2 muM fo

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

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

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

98 The lead compound Debio-1452-NH3 operates as an antibiotic v

99 The lead compound demonstrated potent target inhibition in a

100 This lead compound demonstrated robust Abeta42 reductions and

101 Both leading compounds demonstrated low cytotoxicity and exce

102 The identified lead compound demonstrates significant efficacy and bioa

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

104 formation may provide the first step towards lead compound development for therapeutic drug developme

105 ers to the target protein, in early steps of lead compound development, and this process makes it les

106 l methods can be used to identify anesthetic lead compounds devoid of specific side effects.

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

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

109 Lead compounds discovered have potent and selective anti

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

111 e the selection of taxa for efforts aimed at lead compound discovery.

112 hway a promising endogenous target for novel lead-compounds discovery.

113 ies led to the identification of an emerging lead compound, displaying potency against intracellular

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

115 Our dual agonist lead compound exhibited weak agonism on FXR and PPARdelt

116 led to the identification of five promising lead compounds, exhibiting excellent fungicidal activiti

117 The identified lead compound exhibits significant quadruplex versus dup

118 ggest that 3,4-DCQAME represents a promising lead compound for anti-RSV therapeutic development.

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

120 ully modulated by CEF which could serve as a lead compound for developing treatment for pregabalin ab

121 BCH070 is a promising lead compound for development of new antimalarial combin

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

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

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

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

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

127 reduced structural complexity as a potential lead compound for future autoimmune drug development.

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

129 We identified DBeQ as a promising lead compound for structural optimization aimed at selec

130 thout depolarizing the plasma membrane, as a lead compound for structure-activity profiling.

131 ity of DHAD for Mtb survival, is a potential lead compound for the design of novel anti-TB drugs.

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

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

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

135 y evaluation suggest that 40 may be a viable lead compound for the development of highly subtype-sele

136 lex is a viable drug target, and CPD3.1 is a lead compound for the development of more potent TEAD in

137 suggest that TCMDC-135051 (1) is a promising lead compound for the development of new antimalarials w

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

139 t that levosimendan can be a promising novel lead compound for the development of safe, effective, an

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

141 2.97 muM), thus being considered as a novel lead compound for the discovery of novel effective antit

142 r data suggest that 12j could be a potential lead compound for the treatment of DR, hence deserving f

143 Thus, we propose CMA as a lead compound for therapeutic inhibition of Nef to enhan

144 The lead compound for this study ((3-(N-butylethanimidoyl)et

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

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

147 -based covalent ligand screening to discover lead compounds for challenging targets, which holds prom

148 f a programme that aimed to rapidly discover lead compounds for clinical use, by combining structure-

149 ntimicrobial peptides (PrAMPs) are promising lead compounds for developing new antimicrobials; howeve

150 ial effects in models of AD and may serve as lead compounds for development of AD therapeutic agents.

151 These results identify lead compounds for development of PKCepsilon inhibitors

152 inhibitors for basic research and potential lead compounds for development of therapeutic agents tar

153 ituted cyclobutanes, core components of many lead compounds for drug development.

154 ion were determined to establish them as new lead compounds for flaviviral inhibitors.

155 rm for drug screening, and advance two novel lead compounds for FTD.

156 pectrum antiviral drug target and identifies lead compounds for further development.

157 r in vitro and in vivo studies and promising lead compounds for further optimization.

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

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

160 analysis to provide new chemical probes and lead compounds for novel and druggable targets.

161 of both 1,2-dioxanes and tetrahydropyrans as lead compounds for novel therapies against Leishmania.

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

163 g candidates using nanomole-scale amounts of lead compounds for structure-activity relationship devel

164 and mycobacterial viability and can serve as lead compounds for the development of a new class of ant

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

166 ic cell lines, suggesting their potential as lead compounds for the development of novel antimicrobia

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

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

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

170 l)pyrazoles warrant further investigation as lead compounds for the treatment of CRPC.

171 gical role of the OX1R in vivo and promising lead compounds for the treatment of drug addiction, anxi

172 )pyrazoles, demonstrating their potential as lead compounds for the treatment of prostate cancer.

173 atural products', with potential to generate lead compounds for use in the struggle to combat the ris

174 conclude that QN 23 can be considered as new lead-compound for ischemic stroke treatment.

175 Our results show that a lead compound from this series improves insulin sensitiv

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

177 Lead compounds from one scaffold co-crystallize with hum

178 Improved lead compounds from the adjuvant pipeline are under deve

179 ates enables efficient identification of the lead compounds, from the dynamic combinatorial library v

180 Previously, we have identified a lead compound, furanopyrimidine 2, which contains a (S)-

181 Several lead compounds generated from structural optimization of

182 and murine Ba/F3 cells expressing BCR-ABL1, lead compound GMB-475 induced rapid proteasomal degradat

183 ed to the clinic; however, several promising lead compounds have been identified through screens of s

184 quent improvements to the chemistry of these lead compounds have resulted in the most recent interact

185 quent improvements to the chemistry of these lead compounds have resulted in the most recent interact

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

187 1' sites which led us to identify two potent lead compounds, i.e., vinyl ketones 4h and 4k.

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

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

190 The lead compounds identified are type-IV kinase inhibitors

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

192 rizing agents and has served as an important lead compound in antineoplastic drug discovery.

193 omer of 1,12-Me(2)SPM represents a promising lead compound in developing a treatment aimed at targeti

194 the results presented here suggest that the lead compound in the ink was used as a drier rather than

195 A lead compound in the series, JMS-053 (7-imino-2-phenylth

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

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

198 ttempt in early drug discovery to modify the lead compounds in such a manner that they then have a lo

199 suggest that flavonoids could be utilized as lead compounds in the development of effective nonretino

200 y (EC(50) = 0.67 muM), thus representing new lead compounds in the drug discovery process for the tre

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

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

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

204 where they were found to outperform previous lead compounds including the rocaglate hydroxamate CR-1-

205 Lead compounds increase dCTPase thermal and protease sta

206 The lead compound inhibited DNA gyrase in gel-based assays,

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

208 n of design cycles needed to optimize hit or lead compounds into high-quality chemical probes or drug

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

210 petitive inhibition assays, we show that our lead compound is 9-33 fold selective for BRD4 D1 over th

211 ther cellular experiments indicated that the lead compound is able to permeate into cell nuclei and t

212 tic or heteroaromatic ring-containing hit or lead compounds is one approach toward minimizing design

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

214 brain-penetrant ALK2 inhibitors based on the lead compound LDN-214117.

215 High doses of the initial lead compound led to tumor stasis in an activated B-cell

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

217 peridine derivative S-28 was identified as a lead compound modulating macrophage M2 polarization.

218 Lead compound MT107 (7f) was radiolabeled with carbon-11

219 We identified a lead compound named MP135 that exhibits high G-protein a

220 The lead compounds, named NCATS-SM1440 (43) and NCATS-SM1441

221 Our lead compound neutralizes influenza A group 1 viruses by

222 lectivity indexes (SI > 100) compared to the lead compound niclosamide, while maintaining sub-micromo

223 ter safety windows, compared to those of the lead compound niclosamide.

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

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

226 The lead compound of this series, ML290, was selected based

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

228 tional compounds in which one component is a lead compound or a drug.

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

230 The identified compounds will (i) serve as lead compounds or may be modified to inhibit EBV and pot

231 The resultant lead compounds possess potent activity against a multidr

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

233 nhibited HP1-mediated gene silencing and one lead compound potently inhibited breast tumor growth in

234 etic mutant model of retinitis pigmentosa, a lead compound, Q525, afforded sustained RET activation a

235 Minimum inhibitory concentrations for the lead compounds ranged from 0.125 to 2 mg/L for MDR Gram-

236 tructures with H1 and H5 HAs reveal that the lead compound recapitulates the bnAb hotspot interaction

237 As such, the extent to which current lead compounds represent mechanistically novel, extremel

238 The leading compounds represent viable preclinical candidate

239 Our lead compound resulted from this study, MS48107 (71), di

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

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

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

243 Lead compounds showed inhibition of the HCV pseudopartic

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

245 Cryptosporidium hominis in culture, and our lead compound shows oral efficacy in two cryptosporidios

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

247 es, we have analyzed the interactions of the lead compound SS-31 (elamipretide) with model and mitoch

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

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

250 eover, we discovered DD-03-171, an optimized lead compound that exhibits enhanced antiproliferative e

251 our GABA(A)R model, we identified a class of lead compounds that are N-arylpyrrole derivatives.

252 was used to identify and confirm inhibitory lead compounds that bind to GAS dTDP-rhamnose biosynthes

253 epresent a promising source of antibacterial lead compounds that could help fill the drug discovery p

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

255 32b enriches the arsenal of promising lead compounds that may therefore act as useful pharmaco

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

257 optimization from thienopyrimidine hits to a lead compound, the chemical series leading to the identi

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

259 ells (EC(50) = 24.30 muM) and is a promising lead compound to develop new antiviral treatment for COV

260 s suggest that NFP has the potential to be a lead compound to treat opioid abuse and addiction.

261 platform will enable reliable production of lead compounds to combat AMR.

262 such frameshift inhibitors may be promising lead compounds to combat the current COVID-19 pandemic.

263 These analogues may thus represent lead compounds to develop novel adjuvants improving the

264 e-based design and optimization of quinoline lead compounds to identify FT-2102, a potent, orally bio

265 identification and development of promising lead compounds to serve as inhibitors of Ebola infection

266 ctive natural agonist of PXR and a promising lead compound toward the development of new PXR-regulati

267 underlying the antifibrotic potential of the lead compounds, treatment-dependent changes in the nonco

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

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

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

271 A lead compound was demonstrated to penetrate the blood-br

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

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

274 The design and optimization of lead compounds was based on iterative analysis of X-ray

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

276 Starting from a fragment derived lead compound, we have conducted structure guided optimi

277 , our former gamma-secretase modulator (GSM) lead compound, we utilized sequential structural replace

278 h IC(50) values ranging from 3.1 to 42.3 mum Lead compounds were evaluated against the pathogenic yea

279 These five lead compounds were examined for their synergism/coopera

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

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

282 The lead compounds were rapidly bactericidal with >5 log red

283 Three lead compounds were selected for evaluation of in vivo e

284 Racemic mixtures of identified lead compounds were separated and tested for their stere

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

286 present evidence for preorganization of the lead compound which may contribute to its high affinity

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

288 Importantly, we were able to derive a lead compound with an EC(50) of 7.2 uM and no detectable

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

290 ncept can be applied attempting to replace a lead compound with another candidate.

291 1a (KB2115), a thyroid hormone analog, as a lead compound with low micromolar potency.

292 Among them, 12l was the optimal lead compound with potent inhibition activities against

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

294 iates for the rapid preparation of potential lead compounds with biological activity.

295 ne of the principal sources of precursors to lead compounds with direct pharmaceutical application ac

296 Frontrunner lead compounds with good in vitro absorption, distributi

297 pharmacology screens to refinement delivered lead compounds with improved selectivity, appropriate ph

298 LpxC inhibitors were optimized starting from lead compounds with limited efficacy and solubility and

299 obtained; e.g., the combination of all five lead compounds with voriconazole exhibited either synerg

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