Effect of SCH @-@ 722984 on BRAF @-@ mutant melanoma cell lines .
# ::alignments 1-1.1.3 3-1.1.1 4-1.1.1 5-1.1.1.1 6-1.1.1.1.1.r 7-1.1.1.1.1.1.1 9-1.1.4 10-1.1 11-1.1.2.r 12-1.1.2.1.1 16-1.2 17-1.2.1 22-1.2.2.1 23-1.2.2.1.1.r 24-1.2.2.1.1.1.1 26-1.2.2.1.1.1.1 27-1.2.2.1.2.r 28-1.2.2.1.2.2.1.1 30-1.2.2.1.2.2 30-1.2.2.1.2.2.2 30-1.2.2.1.2.2.2.r 31-1.2.2.1.2.1.1.1 32-1.2.2.1.2 33-1.2.2.1.2
(m / multi-sentence
:snt1 (s / sensitive-03~e.10
:ARG0 (c / cell-line~e.3,4
:ARG0-of (s3 / sensitive-03~e.5
:ARG1~e.6 (s4 / small-molecule
:name (n2 / name :op1 "SCH772984"~e.7))))
:ARG1~e.11 (s2 / small-molecule
:name (n / name :op1 "trametinib"~e.12))
:ARG1-of (g / general-02~e.1)
:mod (a / also~e.9))
:snt2 (f2 / figure~e.16 :mod 1~e.17
:ARG1-of (d2 / describe-01
:ARG2 (a2 / affect-01~e.22
:ARG0~e.23 (s5 / small-molecule
:name (n3 / name :op1 "SCH-722984"~e.24,26))
:ARG1~e.27 (c2 / cell-line~e.32,33
:mod (m2 / medical-condition
:name (n5 / name :op1 "melanoma"~e.31))
:mod (e / enzyme~e.30
:name (n4 / name :op1 "BRAF"~e.28)
:ARG2-of~e.30 (m3 / mutate-01~e.30)))))))
# ::id a_pmid_2514_2146.65 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok A @ .
# ::alignments 0-1.1
(h / have-li-91 :ARG2 "A"~e.0)
# ::id a_pmid_2514_2146.66 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok IC @ 50 ( nM ) .
# ::alignments 0-1 2-1.1 5-1.2.1
(h / have-percentage-maximal-inhibitory-concentration-01~e.0 :ARG2 50~e.2
:ARG4 (c / concentration-quantity
:unit (n / nanomolar~e.5)))
# ::id a_pmid_2514_2146.67 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok 21 BRAF @-@ mutant melanoma cell lines were exposed to 0 @–@ 10 μM SCH @-@ 722984 ( black bars ) or vemurafenib ( grey bars ) and cell viability determined by ATP @-@ based bioluminescence assay .
# ::alignments 0-1.1.1.1 1-1.1.1.3.1.1 3-1.1.1.3 3-1.1.1.3.2 3-1.1.1.3.2.r 4-1.1.1.2.1.1 5-1.1.1 6-1.1.1 8-1.1 9-1.1.2.r 10-1.1.2.1.2.1.1 12-1.1.2.1.2.1.2 13-1.1.2.1.2.2 14-1.1.2.1.1.1 16-1.1.2.1.1.1 18-1.1.2.1.3.1.1 19-1.1.2.1.3.1 21-1.1.2 22-1.1.2.2.1.1 24-1.1.2.2.3.1.1 25-1.1.2.2.3.1 28-1.1.1 29-1.2.1 30-1.2 31-1.2.2.r 32-1.2.2.2.1.1.1 34-1.2.2.2 35-1.2.2.1 36-1.2.2
(a / and
:op1 (e / expose-01~e.8
:ARG1 (c / cell-line~e.5,6,28 :quant 21~e.0
:mod (m3 / medical-condition
:name (n5 / name :op1 "melanoma"~e.4))
:mod (e2 / enzyme~e.3
:name (n / name :op1 "BRAF"~e.1)
:ARG2-of~e.3 (m2 / mutate-01~e.3)))
:ARG2~e.9 (o / or~e.21
:op1 (s / small-molecule
:name (n2 / name :op1 "SCH-722984"~e.14,16)
:quant (c2 / concentration-quantity
:quant (b / between
:op1 0~e.10
:op2 10~e.12)
:unit (m / micromolar~e.13))
:ARG1-of (d / describe-01
:ARG0 (b2 / bar~e.19
:ARG1-of (b3 / black-04~e.18))))
:op2 (s2 / small-molecule
:name (n3 / name :op1 "vemurafenib"~e.22)
:quant c2
:ARG1-of (d4 / describe-01
:ARG0 (b4 / bar~e.25
:ARG1-of (g2 / gray-02~e.24))))))
:op2 (d2 / determine-01~e.30
:ARG1 (v / viability~e.29
:mod c)
:instrument~e.31 (a2 / assay-01~e.36
:ARG1 (b5 / bioluminescence~e.35)
:ARG1-of (b6 / base-02~e.34
:ARG2 (s3 / small-molecule
:name (n4 / name :op1 "ATP"~e.32))))))
# ::id a_pmid_2514_2146.68 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Results are the mean of three experiments , performed in duplicates ( n = 6 ) .
# ::alignments 0-1 3-1.1 4-1.1.1.r 5-1.1.1.1 6-1.1.1 8-1.1.1.2 9-1.1.1.2.1.r 10-1.1.1.2.1 14-1.1.1.2.1.1
(r / result-01~e.0
:ARG2 (m / mean~e.3
:poss~e.4 (e / experiment-01~e.6 :quant 3~e.5
:ARG1-of (p / perform-01~e.8
:manner~e.9 (d / duplicate~e.10 :quant 6~e.14)))))
# ::id a_pmid_2514_2146.69 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Error bars are standard deviation .
# ::alignments 0-1.2.1 1-1.2 2-1.2.r 3-1.1 4-1
(d / deviate-01~e.4
:ARG1-of (s / standard-02~e.3)
:domain~e.2 (b / bar~e.1
:mod (e / error~e.0)))
# ::id a_pmid_2514_2146.70 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Non @-@ V600E substitutions are denoted in the bar graph for each corresponding cell line ( M420 , BRAF @ L597S ; M381 , BRAF @ V600R , M417 , BRAF @ G466E , M414 , BRAF @ V600K ) .
# ::alignments 0-1.1.1.2 0-1.1.1.2.r 2-1.1.1.1 3-1.1 5-1 6-1.2.r 8-1.2.1 9-1.2 12-1.1.2 12-1.3.1.1 12-1.3.1.2 12-1.3.1.3 12-1.3.1.4 13-1.1.2.1 14-1.1.2.1 16-1.3.1.1.1.1.1 18-1.3.1.1.2.1.1 20-1.3.1.1.2.2.1 23-1.3.1.2.1.1.1 25-1.3.1.2.2.1.1 27-1.3.1.2.2.2.1 30-1.3.1.3.1.1.1 32-1.3.1.3.2.1.1 34-1.3.1.3.2.2.1 37-1.3.1.4.1.1.1 39-1.3.1.4.2.1.1 41-1.3.1.4.2.2.1
(d / denote-01~e.5
:ARG1 (s / substitute-01~e.3
:ARG2 (m / mutate-01 :value "V600E"~e.2 :polarity~e.0 -~e.0)
:ARG1-of (c / correspond-02~e.12
:ARG2 (c2 / cell-line~e.13,14)))
:location~e.6 (g / graph~e.9
:mod (b / bar~e.8))
:ARG1-of (m2 / mean-01
:ARG2 (a / and
:op1 (c3 / correspond-02~e.12
:ARG1 (c4 / cell-line
:name (n / name :op1 "M420"~e.16))
:ARG2 (e / enzyme
:name (n5 / name :op1 "BRAF"~e.18)
:ARG2-of (m3 / mutate-01 :value "L597S"~e.20)))
:op2 (c5 / correspond-02~e.12
:ARG1 (c8 / cell-line
:name (n2 / name :op1 "M381"~e.23))
:ARG2 (e2 / enzyme
:name (n6 / name :op1 "BRAF"~e.25)
:ARG2-of (m4 / mutate-01 :value "V600R"~e.27)))
:op3 (c6 / correspond-02~e.12
:ARG1 (c9 / cell-line
:name (n3 / name :op1 "M417"~e.30))
:ARG2 (e3 / enzyme
:name (n7 / name :op1 "BRAF"~e.32)
:ARG2-of (m5 / mutate-01 :value "G466E"~e.34)))
:op4 (c7 / correspond-02~e.12
:ARG1 (c10 / cell-line
:name (n4 / name :op1 "M414"~e.37))
:ARG2 (e4 / enzyme
:name (n8 / name :op1 "BRAF"~e.39)
:ARG2-of (m6 / mutate-01 :value "V600K"~e.41))))))
# ::id a_pmid_2514_2146.71 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Bar at 1 μM denotes threshold between sensitive and intermediate .
# ::alignments 0-1.1 1-1.1.1.r 2-1.1.1.1 3-1.1.1.2 4-1 5-1.2 6-1.2.1 7-1.2.1.1 8-1.2.1 9-1.2.1.2
(d / denote-01~e.4
:ARG0 (b / bar~e.0
:quant~e.1 (c / concentration-quantity :quant 1~e.2
:unit (m / micromolar~e.3)))
:ARG1 (t / threshold~e.5
:topic (b2 / between~e.6,8
:op1 (s / sensitive-03~e.7)
:op2 (i / intermediate~e.9))))
# ::id a_pmid_2514_2146.72 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Resistant cell lines have IC @ 50 higher than 2 μM .
# ::alignments 0-1.2.1 1-1.2 2-1.2 3-1 4-1 6-1.1 9-1.3 10-1.3.1.1 11-1.3.1.2
(h2 / have-percentage-maximal-inhibitory-concentration-01~e.3,4 :ARG2 50~e.6
:ARG1 (c / cell-line~e.1,2
:ARG0-of (r / resist-01~e.0))
:ARG4 (m / more-than~e.9
:op1 (c2 / concentration-quantity :quant 2~e.10
:unit (m2 / micromolar~e.11))))
# ::id a_pmid_2514_2146.73 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok B @ .
# ::alignments 1-1.1
(h / have-li-91 :ARG2 "B"~e.1)
# ::id a_pmid_2514_2146.74 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Timecourse effects of SCH722984 on the MAPK signaling .
# ::alignments 0-1.3 1-1 2-1.1.r 3-1.1.1.1 4-1.2.r 6-1.2.1.1.1 7-1.2
(a / affect-01~e.1
:ARG0~e.2 (s / small-molecule
:name (n / name :op1 "SCH722984"~e.3))
:ARG1~e.4 (s2 / signal-07~e.7
:ARG0 (p / pathway
:name (n2 / name :op1 "MAPK"~e.6)))
:mod (t / timecourse~e.0))
# ::id a_pmid_2514_2146.75 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok SCH722984 @-@ sensitive M238 , SCH722984 @-@ resistant M233 , were treated in a timecourse manner with 500 nM SCH722984 at 1 , 2 , 6 , 12 , 24 and 48 hours compared to DMSO as solvent control ( C ) @ .
# ::alignments 0-1.1.1.2.1.1.1 0-1.2.1.1 2-1.1.1 2-1.1.1.2 2-1.1.1.2.r 3-1.1.1.1.1 5-1.2.1.1 7-1.1.2 7-1.1.2.2 7-1.1.2.2.r 8-1.1.2.1.1 11-1 14-1.4 15-1.4.r 17-1.2.2.1 18-1.2.2.2 19-1.2.1.1 21-1.3.1.1.1 23-1.3.1.2.1 25-1.3.1.3.1 27-1.3.1.4.1 29-1.3.1.5.1 30-1.3.1 31-1.3.1.6.1 32-1.3.1.1.2 33-1.2.3 34-1.2.3.1.r 35-1.2.3.1.1.1 36-1.3.r 38-1.2.3.1 38-1.2.3.1.2 38-1.2.3.1.2.r
(t / treat-04~e.11
:ARG1 (a / and
:op1 (c / cell-line~e.2
:name (n / name :op1 "M238"~e.3)
:ARG0-of~e.2 (s2 / sensitive-03~e.2
:ARG1 (s / small-molecule
:name (n2 / name :op1 "SCH722984"~e.0))))
:op2 (c2 / cell-line~e.7
:name (n3 / name :op1 "M233"~e.8)
:ARG0-of~e.7 (r / resist-01~e.7
:ARG1 s)))
:ARG2 (s3 / small-molecule
:name (n4 / name :op1 "SCH722984"~e.0,5,19)
:quant (c5 / concentration-quantity :quant 500~e.17
:unit (n5 / nanomolar~e.18))
:ARG1-of (c3 / compare-01~e.33
:ARG2~e.34 (s5 / small-molecule~e.38
:name (n6 / name :op1 "DMSO"~e.35)
:ARG0-of~e.38 (c4 / control-01~e.38
:ARG1 (d / dissolve-01)))))
:time~e.36 (a2 / after
:op1 (a3 / and~e.30
:op1 (t2 / temporal-quantity :quant 1~e.21
:unit (h / hour~e.32))
:op2 (t3 / temporal-quantity :quant 2~e.23
:unit h)
:op3 (t4 / temporal-quantity :quant 6~e.25
:unit h)
:op4 (t5 / temporal-quantity :quant 12~e.27
:unit h)
:op5 (t6 / temporal-quantity :quant 24~e.29
:unit h)
:op6 (t7 / temporal-quantity :quant 48~e.31
:unit h)))
:manner~e.15 (t8 / timecourse~e.14))
# ::id a_pmid_2514_2146.76 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Phosphorylated or total MEK , ERK1 @/@ 2 , RSK , AKT , or beta @-@ actin as loading control were determined by western blot analysis .
# ::alignments 0-1.1.1.1.2 1-1.1 2-1.1.2.1.2 3-1.1.1.1.1.1 3-1.1.2.1.1.1 5-1.1.1.2.1.1 5-1.1.2.2.1.1 7-1.1.1.2.1.1 7-1.1.2.2.1.1 9-1.1.1.3.1.1 9-1.1.2.3.1.1 11-1.1.1.4.1.1 11-1.1.2.4.1.1 13-1.1 14-1.1.3.1.1 16-1.1.3.1.1 18-1.1.3.2.1 19-1.1.3 19-1.1.3.2 19-1.1.3.2.r 21-1 22-1.2.r 23-1.2.1 24-1.2.1 25-1.2
(d / determine-01~e.21
:ARG1 (o / or~e.1,13
:op1 (a / and
:op1 (e / enzyme
:name (n / name :op1 "MEK"~e.3)
:ARG3-of (p / phosphorylate-01~e.0))
:op2 (e2 / enzyme
:name (n2 / name :op1 "ERK1/2"~e.5,7)
:ARG3-of p)
:op3 (e3 / enzyme
:name (n3 / name :op1 "RSK"~e.9)
:ARG3-of p)
:op4 (e4 / enzyme
:name (n4 / name :op1 "AKT"~e.11)
:ARG3-of p))
:op2 (a2 / and
:op1 (e8 / enzyme
:name (n8 / name :op1 "MEK"~e.3)
:mod (t / total~e.2))
:op2 (e7 / enzyme
:name (n7 / name :op1 "ERK1/2"~e.5,7)
:mod t)
:op3 (e6 / enzyme
:name (n6 / name :op1 "RSK"~e.9)
:mod t)
:op4 (e5 / enzyme
:name (n5 / name :op1 "AKT"~e.11)
:mod t))
:op3 (p2 / protein~e.19
:name (n9 / name :op1 "beta-actin"~e.14,16)
:ARG0-of~e.19 (c / control-01~e.19
:ARG1 (l / load-01~e.18))))
:manner~e.22 (a3 / analyze-01~e.25
:manner (i / immunoblot-01~e.23,24)))
# ::id a_pmid_2514_2146.77 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok C @ .
# ::alignments 1-1.1
(h / have-li-91 :ARG2 "C"~e.1)
# ::id a_pmid_2514_2146.78 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok Effects of SCH722984 on the MAPK signaling at 24 hours .
# ::alignments 0-1 1-1.1.r 2-1.1.1.1 3-1.2.r 5-1.2.1.1.1 6-1.2 8-1.3.1.1 9-1.3.1.2
(a2 / affect-01~e.0
:ARG0~e.1 (s / small-molecule
:name (n / name :op1 "SCH722984"~e.2))
:ARG1~e.3 (s2 / signal-07~e.6
:ARG0 (p / pathway
:name (n2 / name :op1 "MAPK"~e.5)))
:time (a / after
:quant (t / temporal-quantity :quant 24~e.8
:unit (h / hour~e.9))))
# ::id a_pmid_2514_2146.79 ::amr-annotator SDL-AMR-09 ::preferred
# ::tok SCH722984 @-@ sensitive M262 , SCH722984 @-@ resistant M381 , SCH722984 @-@ intermediately sensitive M409 cells were treated for 24 h with DMSO as solvent control (-) or 500 nM SCH722984 (+) .
@ @