ライフサイエンスコーパス: HIT

1 eatment of heparin-induced thrombocytopenia (HIT).

2 ); empirical PG x E=1.2 x 10(-8)) as the top hit.

3 each year, and just 7% of shallows were not hit.

4 ted thrombosis during DOAC therapy for acute HIT.

5 ith the ubiquitin ligase Nedd4-1 being a top hit.

6 derivative, was characterized as a positive hit.

7 etylase activity, scored as a significant SB hit.

8 and discovered an aryloxazole-based anti-HCV hit.

9 dic system that simulate the pathogenesis of HIT.

10 system, was identified as the most promising hit.

11 of the different anticoagulants for treating HIT.

12 nally, compound P-902 was identified as best hit.

13 icro1) of the clathrin adaptor AP-1 as a top hit.

14 multitude of data, including false-positive hits.

15 confined subsets of PAINS produced abundant hits.

16 n human and rabbit sera and identify epitope hits.

17 probing the SAR around one or more fragment hits.

18 positives that permeate the pool of initial hits.

19 ld benefit from an easy way to mark positive hits.

20 sterase activity and identified 714 positive hits.

21 ompounds, and generates a high percentage of hits.

22 f dose-response curves of the most promising hits.

23 synthesis, out of 593 hits, 39 were left top hits.

24 d screening in the context of false-positive hits.

25 0,842 assembled transcripts and 30,518 BLAST hits.

26 imization of high-throughput screening (HTS) hit 1 led to the identification of 3, which demonstrated

27 From a single hit (12) validated by biochemical and biophysical assays

28 a first screening experiment, we identified hit 13 as able to inhibit STAT5 phosphorylation and leuk

29 ed on the thesis that a series of mutational hits (1st Hit) at the stem-cell level generates a clone

30 rein, we describe optimization of an initial hit 2, resulting in identification of racemic-trans-(3-(

31 A series of additional mutational hits (2nd Hit) transforms the expanding clone into cance

32 stance mechanism of M. smegmatis against one hit, 3-bromo-N-(5-nitrothiazol-2-yl)-4-propoxybenzamide

33 ssibility for chemical synthesis, out of 593 hits, 39 were left top hits.

34 sp(3) character of high-throughput screening hit 40 afforded a novel morpholinopyrimidone mGlu5 NAM s

35 sing rivaroxaban for serologically confirmed HIT (4Ts score >/=4 points; positive platelet factor 4 [

36 Starting from HTS hit 5, IDO-1 inhibitor 6 (EOS200271/PF-06840003) has bee

37 We report the optimization of fragment hit 5b to 13-d as a biased, potent inhibitor of the BRD

38 Hit 7a and lead 7ii both showed synergistic effects in c

39 ide evidence that maternal immune activation hits a key neurodevelopmental process, the excitatory-to

40 ounds) identified a further approximately 90 hits across three quinolone subtemplates.

41 GWAS identified one genome-wide significant hit (Affymetrix id 1:64178756_C_T; P=1.36 x 10(-11)).

42 thiazole (1), which had been identified as a hit against Trypanosoma brucei, the causative agent of h

43 LI): LPS-induced inflammatory injury and two-hit ALI caused by suboptimal mechanical ventilation and

44 Unusually, the top 3 hits all contained stop codons in the randomized region

45 Surprisingly, under conditions of LPS double-hit an interference of a postulated alpha7nAChR - ferrop

46 ospitalized patients who were diagnosed with HIT, an at least intermediate clinical HIT-risk (4Ts sco

47 l structure of caspase-7 bound to a fragment hit and a thorough kinetic characterization of a zymogen

48 ated and utilized as complementary tools for hit and lead optimizations in drug discovery.

49 One of them was selected as a hit and optimized by a structure-activity relationship a

50 fatal accidents, it did decrease the rate of hit and run accidents, suggesting that the policy reduce

51 Hit and run behaviors often delay emergency assistance,

52 (50 compounds) identified approximately 100 hits and four distinct chemotypes, the most promising of

53 s provide great supporting evidence for GWAS hits and important insights into the regulatory pathways

54 s faster than a popular artificial centering hit-and-run algorithm, enabling reliable and tractable s

55 This work demonstrates that hit-and-run epigenetic events can prevent senescence ent

56 algorithm is based on the provably efficient hit-and-run random walk and crucially uses a preprocessi

57 tion of a new sampling algorithm, coordinate hit-and-run with rounding (CHRR).

58 s on transcriptional regulation such as the "hit-and-run" model and transcription bursting that could

59 ic inhibitors, the high-throughput screening hit anthranilic acid 4, the known benzofuran analogue 5,

60 ombus endothelium is the predominant site of HIT antigen assembly.

61 After a few minutes, HIT antigen was detected within the thrombus itself at t

62 bound to peri-injury endothelium and formed HIT antigenic complexes that were dissociated by heparin

63 Up to 68% of the hits are chemotypes described for the first time as late

64 Given that most GWAS hits are in putative regulatory regions and transcript a

65 f the coinhibitory molecule PD-1, additional hits are required.

66 patients who received DOAC therapy for acute HIT as either primary therapy (group A) or secondary the

67 ticoagulant with transition to a DOAC during HIT-associated thrombocytopenia).

68 cessful outpatient rivaroxaban management of HIT-associated thrombosis.

69 thesis that a series of mutational hits (1st Hit) at the stem-cell level generates a clone with repli

70 Two hits, ATA and NF023, obtained in both screens were confi

71 The top hits based on the combined data-replication factor C3 (R

72 applicable process for identifying degrader hits based on the serine/threonine kinase TANK-binding k

73 In 2015-2016, both regions were hit by another drought.

74 will summarize our current understanding of HIT by reviewing pathogenesis, essential clinical and la

75 and analyzing the effects of off targets on hit calling.

76 We show that fragment hits can be advanced to furnish selective ligands that a

77 We also searched for potential "multiple-hit" cases; one proband carried a rare AUTS2 variant in

78 itre RSV type-A and B infections that seeded HiT clades in the subsequent year.

79 s were identified that we termed High Titre (HiT) clades of RSV.

80 trol continuum, measuring interventions that hit clinically related targets, and leveraging technolog

81 d Pyicoclip, on four publicly available Ago2-HITS-CLIP datasets and one unpublished in-house Ago2-dat

82 Peaks identified by HITS-CLIP were verified as true NP binding sites based o

83 solated by crosslinking immunoprecipitation (HITS-CLIP), we identified the vRNA binding profiles of N

84 Using HITS-CLIP, we map HuR and miRNA binding sites on human 3

85 ated with AF populations, with the strongest hits clustering on chromosome 4q25, close to the gene fo

86 Initial hit compound (Z)-5-((1-(4-bromophenyl)-2,5-dimethyl-1H-p

87 ization of the benzene-sulfonamide in silico hit compound 3.

88 T interaction domain identified one positive hit compound and two analogs of the hit with high cytoto

89 Further characterization of the top hit compound revealed its ability to induce a dose-depen

90 report the discovery of a promising initial hit compound targeting the Fanconi anemia ubiquitin-conj

91 in, we report the optimization process for a hit compound that has emerged from a phenotypic screen r

92 Optimization of the hit compound, identified in a NF-kappaB reporter gene as

93 The most potent hit compound, N-[4-(diethylamino)phenyl]-5-methyl-3-phen

94 On the basis of a Weinreb amide hit compound, we designed and synthesized a diverse set

95 obtained X-ray structures of the most potent hit (compound 19, IC50 = 2.9 muM) in complex with the en

96 ss this concern, here we developed a potent "hit" compound, VSP-51, which is a novel selective PPARga

97 brary of 5,195 small molecules identified 34 hit compounds that interact with the regulatory cyclic n

98 tabolites are emerging as promising starting hit compounds to modulate human targets, hence triggerin

99 Potency optimization of the sulfonamide hit compounds was undertaken as informed by docking stud

100 ological activity in vitro, we identified 21 hit compounds which inhibited IMPalpha/beta1:C binding w

101 ening hits limits our understanding of early hit compounds.

102 Validation of one of these hits, confirmed NT5C (5',3'-Nucleotidase, Cytosolic) as

103 and altered DNA methylation may be a second hit contributing to penetrance.

104 These small-molecule hits demonstrated balanced activities at the targets, mo

105 Fragment hit-derived arylpyrrolo[2,3-b]pyridine LRRK2 inhibitors

106 Seven associated SNPs hit directly on candidate genes; four SNPs were in high

107 Nearly 30% of monitored seabed was hit each year, and just 7% of shallows were not hit.

108 Both noncovalent and covalent hits emerge from such endeavors.

109 i-randomly mutated Oryza sativa FNR, the top hit enabled a 60 % increase in NADPH-driven H2 productio

110 e in lipophilic efficiency from the fragment hit, excellent kinase selectivity, and pharmacokinetic p

111 ositives by selectively identifying positive hits exclusively when a ligand at the binding site of in

112 In this article, we describe two hit finding approaches leading to the discovery of new c

113 tein target is a key component when defining hit-finding strategies or when prioritize among drug tar

114 The pyrrolopyrimidine AEE788 (a hit for anti-HAT drug discovery) associates with three t

115 lowest common ancestors of multiple database hits for each query sequence, and further classification

116 t a concentration of 10 muM, there were many hits for JJC8-016, binding affinities in the range of it

117 w overall, with median values of two to five hits for PAINS tested in hundreds of assays.

118 proliferation of cancer cells and optimized hits for potency and selectivity, both in vitro and in c

119 Several of these hub genes are GWAS hits for traits that might involve dysfunction of brain

120 The screening led to 115 hits for which we determined biochemical IC50, thus iden

121 ing design would have missed, increasing the hit frequency from the chemical library three-fold.

122 The hit frequency was low overall, with median values of two

123 t our lead optimization of a benzoxazepinone hit from a DNA-encoded library and the discovery and pro

124 repeating unit (RU) of ST2 CPS, emerged as a hit from the glycan array screens.

125 et of genes or nucleotide locations, such as hits from an association study.

126 t but also illustrated a unique way in which hits from orthogonal screening approaches complemented e

127 However, oftentimes, picking relevant hits from such screens and generating testable hypothese

128 cidation of the mechanism of action (MoA) of hits from these noisy high-throughput screens remain dif

129 chment for an inputted list of genes (e.g., 'hits' from a screen) and search for additional genes wit

130 Here we investigate whether a "three-hit" (genetic load x environmental factor x sex) theory

131 tients treated with rivaroxaban during acute HIT (group A, n = 25; group B, n = 21); major hemorrhage

132 strated by a case of persisting (autoimmune) HIT (>2-month platelet recovery with inversely parallel

133 The three "hits" had cumulative effects on ultrasonic vocalizations

134 egions) and farmers in these regions will be hit hardest by increasing temperatures.

135 f SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease.

136 Two of these hits (I942 and I178) were selected for their robust and

137 The combination of structure-based hit identification and subsequent optimization of the ce

138 ll, the generated models can support various hit identification tasks, including virtual screening, c

139 gh-throughput screening paradigm facilitated hit identification, while structure-based design and mul

140 vage events can be a cause of false positive hit identification.

141 y in a ligand-efficient manner, a micromolar hit identified from a screen of a Pfizer fragment librar

142 Here we use a 'two-hit' immune-activation paradigm to determine whether per

143 cal and laboratory features confirmed "true" HIT in at least 74 of 195 (38.0%) patients; 35 of 74 (47

144 Hits in deeper water were more deadly, but less frequent

145 in cell cycle regulation, were identified as hits in four different RNAi screens and we therefore stu

146 me-wide association studies revealed 28 GWAS hits in potential candidate genes likely to affect trait

147 activated the default mode network, whereas hits in the picture memory test preferentially engaged t

148 d Tn-Seq associated approaches (e.g. TraDis, HiTS, IN-Seq) and includes fitness (growth rate) calcula

149 more ring structures dominated the screening hits, including nitroaromatic compounds that induce subs

150 e Markov chain models that capture the multi-hit initiation-promotion-malignant-conversion hypothesis

151 ing clinical outcomes in patients with multi-hit injuries.

152 ed, such as excessive inflammation, a second-hit insult, or an imbalance between pro- and anti-inflam

153 of crystallographically intractable fragment hits into more potent binders.

154 Herein we report optimization of the hits into potent small molecule inhibitors (IC50 < 300 n

155 tubal epithelial cells (serving as the first hit) - into pathogenic fibrosis.

156 rting efficacy and safety of DOACs for acute HIT is increasing, with the most experience reported for

157 By proposing that the 1st Hit is largely telomere length-independent, while the 2n

158 y telomere length-independent, while the 2nd Hit is largely TL-dependent, we resolve the paradox, hig

159 Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder initiated by antibodies

160 hreatening heparin-induced thrombocytopenia (HIT) is treated with the alternative nonheparin anticoag

161 Our lead hit, JMJD6, mediates the upregulation of in vivo stress

162 r the western North Pacific, especially that hits Korea and Japan.

163 Highly efficient hits (LE > 0.6) often result.

164 ategy, allowing the generation of innovative hits/leads and successful optimization processes.

165 The molecular combination of these screening hits led to compound 22a (PF-543) with 2 orders of magni

166 biochemical high-throughput screening (HTS) hits led to the discovery of a series of ligands that bi

167 receptor IIA (FcgammaRIIA), infusion of the HIT-like monoclonal antibody KKO increased fibrin and pl

168 rcity of historical ADMET data for screening hits limits our understanding of early hit compounds.

169 discovery cohort, one genomewide significant hit located in phosphodiesterase 4D, cAMP-specif (PDE4D)

170 Purpose Patients with double-hit lymphoma (DHL) rarely achieve long-term survival fol

171 re no published prospective trials in double-hit lymphoma, however retrospective studies strongly sug

172 ch to the evaluation and treatment of double-hit lymphoma, with an eye toward future clinical trials

173 Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DEL

174 ll lymphoma, have been referred to as double-hit lymphomas (or triple-hit lymphomas if all 3 rearrang

175 Patients with double-hit lymphomas have a poor prognosis when treated with st

176 ferred to as double-hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present).

177 Double-hit lymphomas may arise as a consequence of the transfor

178 These double-hit lymphomas may have arisen from a tumor precursor tha

179 nd/or BCL6 rearrangements, so-called "double-hit" lymphomas (HGBL-DH), are aggressive lymphomas that

180 We suggest that multiple genetic hits may act in combination to degrade lysosomal functio

181 Our study identifies a potential "two-hit" mechanism in which tau acetylation disengages tau f

182 In good memory performers (R-hits minus false alarm), the coupling was stronger in R

183 Instruction compliance (R-hits minus NR-hits) was significantly related to negativ

184 These findings challenge the assumed two-hit model of Emu-Myc lymphoma and demonstrate a function

185 viewing LIP-associated autoimmunity as an n-hit model, we suggest a more quantitative view of lympho

186 ility, concavity, and whether it is a single-hit model.

187 the view of LIP-driven autoimmunity as a two hit model; however, not all cofactors have equal ability

188 tion of organoarsenical leads of the natural hit molecule.

189 A third of health-care services were hit more than once.

190 Testing the two-hit mouse model should both add new knowledge to the gro

191 One of the hits, MS0021570_1, was identified as a GPR171 antagonist

192 astic leukemia (cALL) functioning as a first-hit mutation that initiates a clinically silent pre-leuk

193 and early progenitor clones with the "first hit" mutation in APC that subsequently gave rise to both

194 nt improvement over our previously reported "hit" NC9.

195 HIT'nDRIVE aims to solve the "random walk facility locat

196 Overall, HIT'nDRIVE may help clinicians contextualize massive mul

197 to 2200 tumors from four major cancer types, HIT'nDRIVE revealed many potentially clinically actionab

198 Here we introduce HIT'nDRIVE, a computational method that integrates genom

199 Furthermore, HIT'nDRIVE, when applied to a large panel of pan-cancer

200 e prediction for tumor samples by only using HIT'nDRIVE-seeded driver gene modules from gene interact

201 nux is effective and safe in suspected acute HIT; no HIT-specific complications occurred in the fonda

202 ips around one of those previously described hits, NSC 60339 (1).

203 set of the offspring also received a second 'hit' of lipopolysaccharide (LPS), which simulates a bact

204 aged 7-13 years were randomly assigned to a HIT or an active control group matched for enjoyment and

205 hologues computed from reciprocal best BLAST hits or OrthoMCL, and DAGchainer, and outputs an overvie

206 Top hits (P < 5 x 10(-8)) were further evaluated in 291 CAD

207 /obliterative arteriopathy induced via a two-hit pathophysiological mechanism without hypoxia provide

208 his hemisphere as a consequence of a "double-hit" phenomenon because of preexisting alterations in co

209 ients, even among those with a high clinical HIT probability.

210 Human homologs of top-ranked hits protected against alphaSyn-induced cell death in a

211 These hits provide insight into human vertebral segmentation d

212 SAR investigations around the screening hits provided a diverse set of potent agonists at 5-HT2C

213 , for which we obtain novel chemotypes and a hit rate that approaches 40%.

214 sults from the 2015 contest show an improved hit rate when compared to results from the 2014 contest.

215 e) out of seven tested candidates ( 40% true hit rate) as direct inhibitors of VCP/p97 and ERAD.

216 irtual screening campaign yielded a high 32% hit rate, identifying novel fragment-like and lead-like

217 This library had a 2.89% hit rate, with 24 NMNAT2 positive and 13 negative modula

218 placement term can substantially improve the hit rates and ligand geometries from docking screens, al

219 Hit rates are often low, typically around 0.1%, limiting

220 PAINS substructures were detected, and their hit rates were determined.

221 The 6-week HIT regimen resulted in improvements on measures of cogn

222 effect of a 6 week high-intensity training (HIT) regimen on measures of cognitive control and workin

223 n and the requirement for additional genetic hits remain unclear.

224 Further characterization of two hits revealed that the small molecule HDAC inhibitors, I

225 with HIT, an at least intermediate clinical HIT-risk (4Ts score >/=4 points), and received treatment

226 ing kinetic and thermodynamic parameters for hit selection.

227 These profiles allow teams to quickly assess hit series for desirable ADMET properties or suspected l

228 cted VERO cells was used to identify a novel hit series of 5-amino-1,2,3-triazole-4-carboxamides (ATC

229 els to generate in silico ADMET profiles for hit series to enable more complete characterizations of

230 t challenges remain in the prioritization of hit series.

231 ion and profoundly impact the progression of hit series.

232 , we say that a set of k-mers is a universal hitting set (UHS) if every possible L-long sequence must

233 pers to use an ordering based on a universal hitting set or, if not possible, a randomized ordering,

234 By using small universal hitting sets (a recently defined concept), we show how t

235 in adulthood: only mice exposed to all three hits showed deficits in this aspect of social behavior.

236 An analysis of reciprocal best hits shows that 31 genes are conserved between African s

237 cused on validating endosome/Golgi-localized hits specific for STx2 and found that depletion of UNC50

238 The composite endpoint of HIT-specific complications (thromboembolic events, amput

239 Main outcome measures were the incidences of HIT-specific complications (thromboembolic venous/arteri

240 ffective and safe in suspected acute HIT; no HIT-specific complications occurred in the fondaparinux-

241 Here we establish a "two-hit" stress model in mice wherein stress at a specific p

242 Hits synergistically affected social recognition in adul

243 Compound 3i is a potent hit (TBK1 DC50 = 12 nM, Dmax = 96%) with excellent selec

244 This identified a hit that subsequent in vitro analysis showed directly bi

245 mpound libraries identified more than thirty hits that increased MBNL1 expression greater than double

246 Among the hits that passed this screening cascade, a 6-dialkylamin

247 ry of 107 FDA-approved compounds to identify hits that prevented the age-dependent functional deterio

248 en against porcupine revealed several potent hits that were confirmed to be Wnt pathway inhibitors in

249 fy additional genetic factors (i.e., "second hits") that may contribute to schizophrenia expression.

250 In winter 2013/14 a succession of storms hit the UK leading to record rainfall and flooding in ma

251 reet lighting-other drivers can better avoid hitting them, directly reducing the accident rate.

252 m a weakly potent, nonselective pyridazinone hit to deliver high potency for the PCAF/GCN5 bromodomai

253 idine carboxamide series was prioritized for hit to lead optimization.

254 of structure-based drug design enabled rapid hit to lead progression in a program to identify pan-iso

255 egree of sequence similarity of the database hit to the query sequence.

256 od is that the contribution of each database hit to the taxonomic assignment of the query sequence is

257 Using this approach, we successfully used HiTES to activate a silent gene cluster in Streptomyces

258 lly and can enable efficient optimization of hits to potent leads.

259 eles drives MTOR activation; however, second hits to TSC1/TSC2 are not always observed.

260 genetic high-throughput screening approach ("HiTES") to discover small molecule elicitors of silent b

261 e gastrointestinal C. muridarum, as a second hit, to transmucosally convert tubal repairing - initiat

262 ilitate the triage of candidate compounds in hit-to-lead campaigns.

263 tional strategies for fragment screening and hit-to-lead development.

264 eming them as a promising starting point for hit-to-lead development.

265 Traditional hit-to-lead optimization assumes that upon elaboration o

266 Hit-to-lead optimization of a new series of thienopyrimi

267 Herein, we describe the identification and hit-to-lead optimization of a novel class of tricyclic s

268 To assess their applications in the EED hit-to-lead optimization process, large amount of thermo

269 A series of additional mutational hits (2nd Hit) transforms the expanding clone into cancer.

270 urred in all 10 Hamilton patients with acute HIT treated with rivaroxaban.

271 We also performed a literature review of HIT treatment using DOACs (rivaroxaban, apixaban, dabiga

272 stematic series of analogues of the original hit using a structure-based drug design strategy, which

273 le testing (Benjamini-Hochberg) and verified hits using bisulfite PCR pyrosequencing and qPCR.

274 egative pathway components and validated top hits using multiple signaling and differentiation assays

275 ilarity between query sequences and database hits using pairwise sequence alignment.

276 ng sites and optimization of interactions of hits using the structure of the target protein.

277 ted our prospective study of rivaroxaban for HIT), using rivaroxaban for serologically confirmed HIT

278 Structural modifications of identified hit VA240 in synthesized analogues 6-41 afforded compoun

279 The hit validation stage of a fragment-based drug discovery

280 Identification of a sulfoquinoline hit via high throughput screening (HTS) followed by opti

281 The initial pyrrolidine hit was modified by moving the position of the carboxyli

282 d optimization, a 5 microM virtual screening hit was transformed to a series of very potent nanomolar

283 Instruction compliance (R-hits minus NR-hits) was significantly related to negative coupling bet

284 shunt that greatly minimizes false-positive hits, we identify mitoxantrone out of more than 600 clin

285 LCL hits were enriched for EBV-induced genes, including vira

286 The hits were evaluated in biology triage assays to exclude

287 Among the phospho-site hits were known LRRK2 sites as well as two phospho-sites

288 Retrieved hits were screened for inclusion and were evaluated with

289 Top hits were structurally unrelated BETi, including JQ1, I-

290 Four hits were tricyclic antidepressants (TCAs), and they rep

291 Hits were validated by surface plasmon resonance and X-r

292 luciferins, and orthogonal enzyme-substrate "hits" were identified.

293 oic acid (WTA) inhibitors, we identified one hit, which was expanded through chemical synthesis into

294 unity to prevent thrombotic complications of HIT, while sparing systemic hemostatic pathways.

295 The successful application of HiTES will allow future interrogations of the biological

296 positive hit compound and two analogs of the hit with high cytotoxic, pro-apoptotic and anti-mitotic

297 a collection of beta-lactones, we found one hit with potent anti-mycobacterial and bactericidal acti

298 creening of candidates returned 14 confirmed hits with activities in the nano- to low-micromolar rang

299 uberculosis (Mtb) in order to identify novel hits with antitubercular activity.

300 Third, the top hits with p<5.0x10(-6) from the first two stages were co