ライフサイエンスコーパス: kinome

1 chemo-proteomics to annotate the degradable kinome.

2 nique polypharmacological profile across the kinome.

3 understanding of the historically untargeted kinome.

4 d coverage ( approximately 80%) of the human kinome.

5 ize and activate more than half of the human kinome.

6 nase activity and drug resistance across the kinome.

7 the appearance of kinases de novo within the kinome.

8 ificantly influence selectivity in the human kinome.

9 fy quantotypic peptides for 21% of the human kinome.

10 on in the Mycobacterium tuberculosis Ser/Thr kinome.

11 ry RGCs and used it to screen the full mouse kinome.

12 ein kinase as a representative of the entire kinome.

13 ase (AMPK), which defines this branch of the kinome.

14 ti-malarial drug targets within the parasite kinome.

15 covering >80% of the human catalytic protein kinome.

16 nsive loss-of-function screen of the protein kinome.

17 racteristic of kinases in this region of the kinome.

18 esenting >50% of the predicted human protein kinome.

19 on of how inhibitors interact with the human kinome.

20 iminary in silico analysis of the sea urchin kinome.

21 NA interference (RNAi) vectors targeting the kinome.

22 widespread series affinity across the human kinome.

23 o accelerate understanding of TPD beyond the kinome.

24 the interactions between HSP90 and the human kinome.

25 n and conveying selectivity over the broader kinome.

26 he published crystal structures of the human kinome.

27 eed to profile kinase inhibitors against the kinome.

28 at highlights areas of unmet need within the kinome.

29 ise approximately 10% of the human and mouse kinomes.

30 protein kinases, is closer to the Drosophila kinome (239) than the human kinome (518) with respect to

31 of kinase activity assays spanning the human kinome (243 kinases).

32 o the Drosophila kinome (239) than the human kinome (518) with respect to total kinase number.

33 in a regulatory manner, we performed a whole kinome (779 kinases) siRNA screen for positive or negati

34 The human kinome, a major druggable enzyme class has been exploite

35 By exploring chirality within the kinome, a new iteration of kinase inhibitors is being de

36 When we compared the kinome across the six cell lines, representative of diff

37 ffective treatment that attacks the aberrant kinome activation associated with resistance to HER2-tar

38 uantitative proteomics approach, we assessed kinome activity in response to MEK inhibition in triple-

39 By interrogation of kinome activity through an unbiased screen and targeted

40 We applied this unique kinome-activity profiling strategy in a variety of cellu

41 edback between MCL cells and TME, leading to kinome adaptive reprogramming, bypassing the effect of i

42 Toxoplasma has in its kinome among the highest percentage of pseudokinases amo

43 contrast to this similar diminution in mRNA, kinome analyses using a peptide array and DNA-conjugated

44 A peptide assay-based kinome analysis (in which cell lysates are used to phosp

45 A kinome analysis combined with chemical and genetic appro

46 Kinome analysis data reflected this altered host cell ph

47 ling pathway intermediates identified in our kinome analysis inhibited viral replication in vitro and

48 A global kinome analysis of CDK4-deficient mice following insulin

49 signaling intermediates identified from our kinome analysis provided partial protection in a lethal

50 Kinome analysis revealed multiple PtpA-dependent changes

51 phosphorylation events, we employed temporal kinome analysis to investigate the functional responses

52 We employed temporal kinome analysis to investigate the relative early, inter

53 ng pathway intermediates identified from our kinome analysis, also inhibited EBOV replication.

54 The large number of pseudokinases in the kinome and an increasing appreciation that they have cri

55 Kinannote produces a draft kinome and comparative analyses for a predicted proteome

56 also occur in ALL, we sequenced the tyrosine kinome and downstream signaling genes in 45 high-risk pe

57 notype 1b replicon cell line (Luc-1b) with a kinome and druggable collection of 20,779 siRNAs.

58 isms underplaying the regulation between the kinome and EMT require further elucidation to define tar

59 mily of Ser-Thr protein kinases in the human kinome and have diverse roles in broad physiological fun

60 strains representing the non-essential yeast kinome and identified a single kinase gene, ELM1, as nec

61 ng RNA (siRNA) screen targeting the cellular kinome and identified Tousled-like kinases (TLKs) as cel

62 ntified with superior selectivity across the kinome and improvements in in vitro pharmacokinetic prof

63 g 734 kinase genes covering the entire mouse kinome and individually examined their effects on iPSC g

64 s will enable the broad interrogation of the kinome and its inhibitors.

65 gnificant off-target activity in the protein kinome and only weak activity versus PI3Kalpha/gamma lip

66 The tyrosine kinome and phosphatome harbor oncogenes and tumor suppre

67 ng a loss-of-function screening of the human kinome and phosphatome to identify genes suppressing tum

68 in vivo RNAi screen targeting the Drosophila kinome and phosphatome, we identify 11 kinases and phosp

69 Here we present a method to study the global kinome and phosphoproteome in tandem in a model photosyn

70 xamined nucleic acid variations in the human kinome and several known cancer-related genes in breast

71 oxoplasma and Plasmodium of their respective kinomes and phosphoproteomes.

72 Scaffold coverage varied greatly across the kinome, and many scaffolds representing compounds with d

73 ative mass spectrometry to profile proteome, kinome, and phosphoproteome changes in an established mo

74 number of cancer-associated mutations in the kinome, and the progress in developing specific small-mo

75 tegrated into inhibitor discovery across the kinome, and we outline some immediate consequences for s

76 Here, we applied this approach in a human kinome- and phosphatome-wide study to assess how 649 ind

77 challenges and outlook for drugging the PI3 kinome are discussed in the more general context of the

78 The kinomes are stored in a relational database and are acce

79 Kinome array analysis demonstrated that CD28(+)CD151(+)

80 Further, the kinome array analysis identified changes in the activati

81 d by Western blotting, flow cytometry, and a kinome array protocol.

82 on that is highly conserved within the human kinome as demonstrated by our sequence analysis and stru

83 od to examine the reprogramming of the human kinome associated with bone metastasis of prostate cance

84 igand binding modes for the human structural kinome at scale (208 kinases, 1777 unique ligands, and t

85 selectivity over group I PAKs, and the broad kinome, based on unique flexibility of this lipophilic p

86 demonstrate that Cdc37 has a general role in kinome biogenesis.

87 ed by wrapping differences across its target kinome can selectively direct its impact toward a specif

88 han 500 protein kinases comprising the human kinome catalyze hundreds of thousands of phosphorylation

89 uantitative phosphoproteomics with mammalian kinome cDNA library screen.

90 ed kinase inhibition can induce compensatory kinome changes, rendering single therapeutic agents inef

91 Thus, the sea urchin kinome combines the simplicity of a non-duplicated genom

92 The human protein kinome comprises 535 proteins that, with the exception o

93 The human kinome comprises over 800 individual kinases.

94 The results show that the sea urchin kinome, consisting of 353 protein kinases, is closer to

95 The kinome consists of 518 kinases, and every active protein

96 everal classes of signaling molecules, their kinomes contain a large and diverse set of protein kinas

97 uggests that other pseudokinases (10% of the kinome) could also be catalytically active.

98 inase expression and activation have limited kinome coverage.

99 polypharmacology, a large part of the human kinome currently lacks selective chemical probes.

100 -protein interaction networks generated from kinome data could further be used to guide targeted gene

101 analysis and functional network analysis of kinome data revealed that transforming growth factor (TG

102 Upregulation of TGF-beta signaling in the kinome data sets correlated with the upregulation of TGF

103 Mining of the kinome database revealed that a subset of some 46 kinase

104 ve explores the role of chirality to improve kinome druggability and will serve as a resource for pio

105 hed and used to conduct a negative-selection kinome-focused CRISPR screen to identify kinases essenti

106 he complement of Drosophila protein kinases (kinome) for cell cycle functions after gene silencing by

107 is of all known sequences in the A. thaliana kinome found that alphaC helix disorder may be a common

108 Approximately one-third of the Drosophila kinome has been ascribed some cell-cycle function.

109 ted Tyr and Ser/Thr kinases, over 85% of the kinome has been identified to be dysregulated in at leas

110 r, only a very small fraction of the cardiac kinome has been investigated.

111 Structural coverage of the human kinome has been steadily increasing over time.

112 inome; however, only a small fraction of the kinome has been therapeutically targeted in HGSOC.

113 The strategy of 'drugging the cancer kinome' has led to the successful development and regula

114 e kinase complement of the human genome, the kinome, has provided an excellent starting point for und

115 essential functions for the malaria parasite kinome have been reported, the roles of most protein pho

116 ity with frequent alterations in the protein kinome; however, only a small fraction of the kinome has

117 Recent analysis of the Plasmodium falciparum kinome identified several kinases that are entirely uniq

118 ification and comparison with model organism kinomes identified orthologous groups and highlighted ex

119 e have performed multi-omic profiling of the kinome in bladder cancer patients with the goal of ident

120 A recent analysis of the tyrosine kinome in colorectal cancer identified c-fes as one of o

121 e comprehensively characterized the cellular kinome in Hedgehog-challenged murine WT and Smoothened(-

122 ly the arsenite-induced alteration of global kinome in human cells.

123 cell growth, transcriptome, metabolome, and kinome in response to paracrine signals emerging from ir

124 Analysis of the platelet kinome in the context of the kinase phylogenetic backgro

125 study, we explored the role of the tyrosine kinome in the formation of invadopodia in metastatic mel

126 constituting an extensive and diverse sugar kinome in the thermophilic bacterium Thermotoga maritima

127 e protein kinases ( approximately 50% of the kinome) in a cdc37 mutant strain showed that 51 had decr

128 erved only in 8 of the >90 PTKs in the human kinome, including 3 of the 10 Src family kinases and all

129 WNK kinases are unique members of the human kinome, intimately involved in maintaining electrolyte b

130 s (approximately 70% of mammalian structural kinome) into accurate and specific models of their type-

131 ts, but the prediction of mutants across the kinome is challenging.

132 Thus, about half of the human kinome is currently covered with active small molecules.

133 roducing hypotheses that can explain how the kinome is involved in the maintenance of different cellu

134 risingly similar to humans, since the urchin kinome is missing only 4 of 186 human subfamilies, while

135 The distribution of inhibitors across the kinome is uneven.

136 Kinome-knockdown confirmed dependency on ERBB-signalling

137 r beads and mass spectrometry, we mapped the kinome landscape of HGSOC tumors from patients and patie

138 tivity of Cdc37 could dramatically alter the kinome, leading to profound changes in the tau phosphory

139 e delivery and/or expression by performing a kinome-level screen in which, we identified small-molecu

140 We constructed a SILAC-compatible kinome library for scheduled multiple-reaction monitorin

141 er cells with a lentivirus short hairpin RNA kinome library.

142 ased loss-of-function genetic screen using a kinome library.

143 itative assessment of perturbation in global kinome may provide crucial knowledge for elucidating the

144 ter understanding of the disturbances in the kinome network in amyotrophic lateral sclerosis is neede

145 quantitative analysis of the perturbation of kinome of GM00637 human skin fibroblast cells induced by

146 omprehensively the alterations of the global kinome of HEK293T human embryonic kidney cells upon trea

147 his study provides a global insight into the kinome of S. haematobium and should assist the repurposi

148 In this context, we defined here the kinome of S. haematobium using a refined bioinformatic p

149 The kinome of the human malaria parasite Plasmodium falcipar

150 ned the full protein kinase (PK) complement (kinome) of mouse.

151 se in coverage of the enriched Chlamydomonas kinome over coverage found with no enrichment.

152 high selectivity for the GRK2 subfamily in a kinome panel of 104 kinases.

153 For larger "kinome" panels, the partition index allows assessment of

154 king of altered kinases generated from these kinome profile data predicted PIM-1 kinase as a key swit

155 Kinome profiling and cellular studies demonstrate that,

156 latent HIV-1 integration event and position kinome profiling as a research tool to reveal novel mole

157 hanism of sorafenib activity through in situ kinome profiling identified the mitogen-activated protei

158 Moreover, broad kinome profiling is recommended for the development of P

159 -throughput, SILAC-compatible, and MRM-based kinome profiling method and demonstrated that the method

160 Together, our targeted kinome profiling method offers a powerful resource for e

161 In summary, our targeted kinome profiling method provided by far the most compreh

162 The improved kinome profiling methods described here represent an eff

163 Kinome profiling revealed 5-IT to be a potent and select

164 Subsequent functional kinome profiling revealed an increased activation of p38

165 We use phosphoproteomics and kinome profiling to identify the molecular mechanisms of

166 Moreover, kinome profiling uncovers disruption of multiple signal

167 Kinome profiling versus more than 300 kinases in vitro a

168 The KAYAK (Kinase ActivitY Assay for Kinome profiling) assay measures the phosphorylation rat

169 ellular phosphorylation events (often called kinome profiling).

170 dvanced analysis tools are yet available for kinome profiling.

171 as compared to classical analysis tools for kinome profiling.

172 (n = 15), were analyzed for inflammation and kinome-related gene regulation.

173 93 showed no off-target activities within a kinome-representative mini kinase panel, with favorable

174 Unbiased transcriptional and kinome reprogramming analyses from selected treatment ti

175 ed by far the most comprehensive dataset for kinome reprogramming associated with melanoma progressio

176 M)-based targeted proteomic method to assess kinome reprogramming during melanoma metastasis in three

177 but lost its direct antitumor effects due to kinome reprogramming, which resulted in suppression of p

178 ion of proteasomal c-Myc degradation blocked kinome reprogramming.

179 relative early, intermediate, and late host kinome responses to EBOV infection in human hepatocytes.

180 The average sensitivity and precision for kinome retrieval from the test species are 94.4 and 96.8

181 nalysis of the mutation catalog in the human kinome revealed the presence of cancer-associated mutati

182 c targets, we performed an unbiased tyrosine kinome RNA interference screen in primary cell cultures

183 From a human kinome RNAi screen, we have identified Lats2 kinase as a

184 Through a metabolism-related kinome RNAi screen, we identified inositol-trisphosphate

185 therapeutic efficacy of RITs, we conducted a kinome RNAi sensitization screen, which identified disco

186 m publicly available inhibitors of the human kinome, scaffolds and cyclic skeletons were systematical

187 ith protein tyrosine kinases is conducted on kinome scale by using evolutionary analysis and fingerpr

188 Further kinome-scale siRNA screening demonstrated that SRC MEK5

189 Based on a kinome scan, here we show that Pz-1 is also a potent (IC

190 Using a kinome screen and a systems biology approach, we identif

191 Using an ORF kinome screen in MCF-7 cells treated with the CDK4/6 inh

192 In a recent high-throughput kinome screen in NF2-null human arachnoidal and meningio

193 An RNAi-based kinome screen revealed that LYN is required for growth o

194 e of intracellular signaling, we performed a kinome screen using a label-free assay and found that me

195 Here using an unbiased siRNA kinome screen, we identify and validate casein kinase 1a

196 Kinome screening experiments indicated that NiPp inhibit

197 creen the P. berghei kinome, using published kinome screens for comparison.

198 In Ambit kinome screens, cell growth inhibition studies, and surr

199 Furthermore, we developed a kinome selective irreversible inhibitor 45a with an IC50

200 ines being particularly ligand efficient and kinome selective, and having an improved safety pharmaco

201 emphasize the outstanding properties of the kinome-selective JAK inhibitor CP-690550, as well as the

202 21i (AC081), two structurally novel, potent, kinome-selective pan-Aurora inhibitors.

203 Development of a series of highly kinome-selective spleen tyrosine kinase (Syk) inhibitors

204 ora A inhibitor (IC50 = 2 nM) with very high kinome selectivity for Aurora kinases.

205 ded an understanding of the binding mode and kinome selectivity of the chemical series.

206 (S)-15 demonstrated both a favorable kinome selectivity profile and target engagement in a ce

207 ibitor optimization gave compounds with high kinome selectivity that prevented endoplasmic reticulum

208 tent LRRK2 inhibitors, focusing on improving kinome selectivity using a surrogate crystallography app

209 Pharmacokinetic properties and kinome selectivity were optimized, resulting in the iden

210 ibitor, BIIB068 (1), which demonstrated good kinome selectivity with good overall drug-like propertie

211 In addition to unprecedented JAK isoform and kinome selectivity, 11 shows excellent pharmacokinetic p

212 razines, to a potent example with reasonable kinome selectivity, including selectivity for JAK3 versu

213 d with Cys-1039 of CDK12, exhibits excellent kinome selectivity, inhibits the phosphorylation of seri

214 f kinase therapeutics with high efficacy and kinome selectivity, thus avoiding problems observed with

215 while maintaining BRD4 activity and overall kinome selectivity.

216 Data from this first siRNA-kinome sensitizer screen suggests that inhibiting WEE1 i

217 Cancer kinome sequencing studies have identified several protei

218 Assessment of the phospho-kinome showed decreased phosphorylation of pathways invo

219 Furthermore, a synthetic lethal kinome shRNA screen with a pan-ERBB inhibitor, AZD8931,

220 B4 mutations can induce broad changes in the kinome signature of lung cancer cells.

221 Screening libraries of kinome siRNA and small molecules, we defined PLK1 as an

222 ST and melanoma cells using a human tyrosine kinome siRNA screen.

223 In accordance with the chemical screen, kinome small interfering RNA high throughput screens ide

224 ucture-binding relationships in the tyrosine kinome space in which evolutionary analysis of the kinas

225 mined by their phylogenetic proximity in the kinome space or differences in the interactions with the

226 e interrogation of all elements of the human kinome supporting EGF-dependent signaling.

227 architecture of the M. tuberculosis Ser/Thr kinome that could enable horizontal signal spreading.

228 Taken together, we uncover a circadian kinome that potentially shapes the temporal pattern of t

229 focusing on mutations in the kinase genome (kinome) that lead to tumorigenesis.

230 ein kinase A is the prototype for the entire kinome, these findings may serve as a paradigm for descr

231 R2) inhibitors involves reprogramming of the kinome through HER2/HER3 signaling via the activation of

232 se of high-throughput screening of the yeast kinome to facilitate the major task of identifying human

233 y, we performed an siRNA-based screen of the kinome to identify genetic regulators of PGRN levels in

234 mechanism of action of RepSox, we performed kinome-, transcriptome-, and proteome-profiling and disc

235 ved models are evenly distributed across the kinome tree, allowing reliable profiling prediction for

236 rotein and lipid kinases, leaving 70% of the kinome untapped.

237 kinase complement of the human genome (the "kinome") using public and proprietary genomic, complemen

238 of this resource, we rescreen the P. berghei kinome, using published kinome screens for comparison.

239 Relying on extensive human kinome vetting, we show that (R)-3 is the most potent an

240 NAi) screen targeting 542 genes of the human kinome was used to discover regulators of RNAi.

241 Through a functional screen of the human kinome, we found that mammalian sterile 20-like kinase 1

242 Through RNAi screening of the kinome, we have identified Misshapen (Msn) and the mamma

243 , by conducting a shRNA screen targeting the kinome, we identified PIM1, a non-essential serine-threo

244 Through a systematic evaluation of the kinome, we identified Pro455 and Asn457 in the Syk ATP b

245 ove our understanding of HIF-1 regulation by kinome, we screened a kinase-specific small interference

246 achieve sufficient accuracy for large-scale kinome wide inhibitor selectivity profiling.

247 ymatic assays, chemical proteomic profiling, kinome-wide activity surveys and MTH1 co-crystal structu

248 Finally, we present the kinome-wide analysis of mRNA expression dynamics induced

249 Our calculations predict a kinome-wide conformational plasticity, and indicate the

250 A kinome-wide CRISPR-Cas9 knockout screen reveals that FZD

251 e presented approach opens possibilities for kinome-wide discovery of specific molecules targeting in

252 l of multiple endocrine neoplasia type 2 and kinome-wide drug profiling, here we identify that AD57 r

253 hese agents, we have undertaken a systematic kinome-wide effort to profile their selectivity and pote

254 Using a chemogenomics approach marrying kinome-wide inhibitory profiles of a compound library wi

255 We further reported a kinome-wide landscape of pharmacogenomic interactions by

256 computational oncoproteomics approach, named kinome-wide network module for cancer pharmacogenomics (

257 from an in vivo tumorigenesis screen using a kinome-wide open reading frames (ORFs) library.

258 e inhibitors that have been profiled on near-kinome-wide panels of protein kinases.

259 In turn, through a kinome-wide phosphoproteomic and MS study, we demonstrat

260 tudies establish the feasibility of tyrosine kinome-wide phosphorylation profiling and point to SRC a

261 Combining kinase-focused chemistry, kinome-wide profiling and Drosophila genetics provides a

262 e, we desired to increase the throughput for kinome-wide profiling.

263 A kinome-wide reverse genetics strategy identified 36 para

264 mbine global phospho-proteomic analysis with kinome-wide reverse genetics to assess the importance of

265 l components of this pathway, we performed a kinome-wide RNA interference (RNAi) screen in Drosophila

266 A kinome-wide RNA interference screen was used to identify

267 to gammaherpesvirus through two independent kinome-wide RNA interference screens.

268 Here we report the results of a kinome-wide RNAi screen for cellular pathways involved i

269 A recent kinome-wide RNAi screen with 176 individual bloodstream

270 Using unbiased kinome-wide RNAi screening followed by thorough validati

271 Here, we report a kinome-wide RNAi-based analysis to identify kinases that

272 The kinome-wide screen demonstrated a strong inverse correla

273 a inhibitors were further characterized in a kinome-wide screen demonstrating narrow spectrum profile

274 In a kinome-wide screen of 468 protein kinases, HS-243 had ex

275 11 was highly selective in an in vitro kinome-wide screen, but cellular engagement assays defin

276 Here, through a kinome-wide screen, we found that glycogen synthase kina

277 ical properties and notable selectivity in a kinome-wide screen.

278 Based on these new kinome-wide screening results, we report that GW296115 i

279 Kinome-wide screening would have the advantage of provid

280 These kinome-wide screens, performed within a day on a small c

281 s illustrate for the first time the use of a kinome-wide selective radioactive chemical probe for end

282 motif is accommodated by many human kinases, kinome-wide selectivity of resultant molecules can be po

283 Kinome-wide selectivity profiling of 11 kinase drug cand

284 Kinome-wide selectivity profiling of the library resulte

285 arse and are generally characterized by poor kinome-wide selectivity.

286 a potent pan-PI5P4K inhibitor with excellent kinome-wide selectivity.

287 A kinome-wide sequence alignment highlighted a poorly cons

288 Kinome-wide sequence mining revealed rare presentation o

289 We performed a kinome-wide siRNA screen and identified 70 kinases alter

290 gulators of Shank3 abundance, we performed a kinome-wide siRNA screen and identified multiple kinases

291 Here, a comprehensive kinome-wide siRNA screen in a human HeLa cell-based mode

292 A kinome-wide siRNA screen showed that the insulin recepto

293 In this study, we used a kinome-wide siRNA screen to identify kinases that, when

294 A kinome-wide siRNA screen using a library targeting 720 k

295 as were other protein kinases identified by kinome-wide siRNA screening and a genetic gain-of-functi

296 d a functional kinomics approach including a kinome-wide siRNA-phosphoproteomic screen, a high-conten

297 We therefore conducted a kinome-wide small interfering RNA (siRNA) lethality stud

298 tly label a broad swath of the intracellular kinome with high efficiency.

299 cted a siRNA screening targeted to the human kinome with the aim of discovering new EMT effectors.

300 selection of kinases from each branch of the kinome, with and without known substrates, highlighting