Ceritinib (LDK378)

For research use only. Not for use in humans.

目录号:S7083

Ceritinib (LDK378) Chemical Structure

CAS No. 1032900-25-6

Ceritinib (LDK378)是一种有效的ALK抑制剂,在无细胞试验中IC50为0.2 nM。Ceritinib (LDK378)还可抑制IGF-1RInsRSTK22DFLT3对应的IC50值分别为8 nM、7 nM、23 nM和60 nM。Phase 3。

规格 价格 库存 购买数量  
RMB 1182.86 现货
RMB 3868.47 现货
RMB 10720.71 现货
有超大折扣

今日订购,明日送达,全国免运费!

全国免费电话:400-668-6834   |   Email:info@selleck.cn

客户使用Selleck生产的Ceritinib (LDK378)发表文献64篇:

产品安全说明书

ALK抑制剂选择性比较

生物活性

产品描述 Ceritinib (LDK378)是一种有效的ALK抑制剂,在无细胞试验中IC50为0.2 nM。Ceritinib (LDK378)还可抑制IGF-1RInsRSTK22DFLT3对应的IC50值分别为8 nM、7 nM、23 nM和60 nM。Phase 3。
特性 不与c-Met交叉反应,对体内葡萄糖稳态比TAE684效果好,有效作用于 Crizotinib复发的肿瘤。
靶点
ALK [1]
(Cell-free assay)
Insulin Receptor [1]
(Cell-free assay)
IGF-1R [1]
(Cell-free assay)
STK22D [1]
(Cell-free assay)
FLT3 [1]
(Cell-free assay)
0.2 nM 7 nM 8 nM 23 nM 60 nM
体外研究

LDK378作用于Ba/F3-NPM-ALK和Karpas290细胞,具有显著的抗增殖活性,IC50分别为26.0 nM 和 22.8 nM,作用于Ba/F3-Tel-InsR 和Ba/F3-WT细胞,IC50分别为319.5 nM 和 2477 nM。[1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Parental(+IL3) NV3V[3F{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIHyboU4OiCq MYTEUXNQ NGXVd2FKSzVyPUG1PFYhyrFiMUezJI5O NHrWbWs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe0PVA{PCd-MkW3OFkxOzR:L3G+
WT 70 NUXlVldtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVu3NkBp MYnEUXNQ MVXJR|UxRTJzINMxJFghdk1? Mn7pQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5NEmwN|QoRjJ3N{S5NFM1RC:jPh?=
G1128S 1022 MmTCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHHQfJM4OiCq MYHEUXNQ MVzJR|UxRTFyMjFCtUA{QCCwTR?= NUfrVYdkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3OFkxOzRpPkK1O|Q6ODN2PD;hQi=>
C1156F 1293 NWnVcnp1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkfGO|IhcA>? NUDMbHRITE2VTx?= MX\JR|UxRTJzNzFCtUAyOTVibl2= MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd2OUCzOEc,OjV5NEmwN|Q9N2F-
I1171N 519 M2PJPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIThSno4OiCq MnLRSG1UVw>? NIXZTJhKSzVyPUG4O{DDuSB6NzDuUS=> MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd2OUCzOEc,OjV5NEmwN|Q9N2F-
I1171T 445 NYnD[XgyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXPFSWl[PzJiaB?= NVnRUppDTE2VTx?= MX\JR|UxRTh{INMxJFEzKG6P M3ntclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{S5NFM1Lz5{NUe0PVA{PDxxYU6=
F1174I 184 MmP0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mm\qO|IhcA>? NVy2UnpXTE2VTx?= Mn;iTWM2OD1zMzFCtUAxNjFibl2= NWOxempzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3OFkxOzRpPkK1O|Q6ODN2PD;hQi=>
N1178H 169 NULZNlgxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn7zO|IhcA>? MnfVSG1UVw>? MUDJR|UxRTR{INMxJFYhdk1? M1W0bVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{S5NFM1Lz5{NUe0PVA{PDxxYU6=
E1210K 748 M3vheGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoD4O|IhcA>? MlHqSG1UVw>? Ml3TTWM2OD1zOEegxtEhQDRibl2= NIHke5A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe0PVA{PCd-MkW3OFkxOzR:L3G+
C1156F/D1203N 2809 NHnNU3VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoTRO|IhcA>? M2\WOmROW09? MYPJR|UxRTJ3NDFCtUA6QSCwTR?= MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd2OUCzOEc,OjV5NEmwN|Q9N2F-
Ba/F3 NA WT MlP1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4LwS|czKGh? Ml;6TWM2OD1yLkCyNEDPxE1? M4W1XVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{K3OFAxLz5{NUeyO|QxODxxYU6=
Ba/F3 NA C1156Y NXfCUGY{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV3Ve5dlPzJiaB?= M1PJW2lEPTB;MD6wO|Eh|ryP MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd{N{SwNEc,OjV5Mke0NFA9N2F-
Ba/F3 NA L1196M M3vrc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFXzeoQ4OiCq NXTSUI5UUUN3ME2wMlA1OiEQvF2= M{jlT|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{K3OFAxLz5{NUeyO|QxODxxYU6=
Ba/F3 NA L1152R M1LJNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXO3NkBp NXjWcZVvUUN3ME2wMlI5QCEQvF2= NIW0XJU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyO|QxOCd-MkW3Nlc1ODB:L3G+
Ba/F3 NA G1202R MoPYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEHZNXM4OiCq MkfFTWM2OD1yLkK3O{DPxE1? M2PiNVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{K3OFAxLz5{NUeyO|QxODxxYU6=
Ba/F3 NA G1269A MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4PhTFczKGh? NEjvXXJKSzVyPUCuNFE6KM7:TR?= MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd{N{SwNEc,OjV5Mke0NFA9N2F-
Ba/F3 NA S1206Y M3yzemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX;CRoIxPzJiaB?= NIK1OFhKSzVyPUCuNFM4KM7:TR?= MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd{N{SwNEc,OjV5Mke0NFA9N2F-
Ba/F3 EA WT Mn31S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3[zS|czKGh? MonCTWM2OD1yLkCyNUDPxE1? M4\Bb|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{K3OFAxLz5{NUeyO|QxODxxYU6=
Ba/F3 EA C1156Y MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlP3O|IhcA>? MV\JR|UxRTBwMEK2JO69VQ>? NVXvRYJmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3Nlc1ODBpPkK1O|I4PDByPD;hQi=>
Ba/F3 EA L1196M NX36fXF7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXXsendTPzJiaB?= NH3McWNKSzVyPUCuNFE6KM7:TR?= MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd{N{SwNEc,OjV5Mke0NFA9N2F-
Ba/F3 EA L1152R NHHhZ5NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVqy[plSPzJiaB?= MkLTTWM2OD1yLkC5PUDPxE1? NWX2bWVkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3Nlc1ODBpPkK1O|I4PDByPD;hQi=>
Ba/F3 EA G1202R NHrrZ4JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmTGO|IhcA>? MnXzTWM2OD1yLkS2O{DPxE1? NIjCfXA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyO|QxOCd-MkW3Nlc1ODB:L3G+
Ba/F3 EA G1269A NGLNWnpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXi3NkBp M3\2UGlEPTB;MD6wN|Mh|ryP M1zJdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{K3OFAxLz5{NUeyO|QxODxxYU6=
Ba/F3 EA S1206Y NVe1NHQ5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH;HXFY4OiCq MoTuTWM2OD1yLkCzPEDPxE1? NUjVRZV5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3Nlc1ODBpPkK1O|I4PDByPD;hQi=>
BAF3 NV;zO4FpSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= M2L1UlczKGi{cx?= NFHMWnFCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JI1wfXOnIFLBSlMh[2WubIOgbIFz[m:{aX7nJGVOVDRvQVzLJIFnfGW{IEeyJIhzeyCkeTDTVmIhd3JiQ1PLPEBie3OjeTygTWM2OCB;IECuNFExPyEQvF2u NEfLfYU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUK4PFk1OCd-MkmyPFg6PDB:L3G+
NCI-H3122 MYPBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? NHTCbY44OiCqcoO= NWPKdYVDSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDOR2kuUDNzMkKgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KEOnbHzUbZRmei2JbH:gUJVucW6nc3PlcpQhS2WubDDWbYFjcWyrdImgRZN{[XluIFXDOVAhRSByLkCxOUDPxE1w M2DGeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NU[4Nlg6Lz5{NkW2PFI5QTxxYU6=
NCI-H2228 MYjHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M2PoT|Mh\GG7cx?= MnXWS5Jwf3SqIHnubIljcXSrb36gc4YhcHWvYX6gUmNKNUh{MkK4JINmdGy|IHHmeIVzKDNiZHH5d{BjgSCudX3pcoV{[2WwY3WtZoF{\WRiQ3XscHRqfGW{LVfsc{Bie3OjeTygTWM2OCB;IECuNFE2KM7:TT6= M2mxOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NkK3O|I2Lz5{OU[yO|czPTxxYU6=
SU-DHL1 NVXCNIk6T3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= MoXJN{Bl[Xm| MV;Hdo94fGhiaX7obYJqfGmxbjDv[kBpfW2jbjDTWU1FUExzIHPlcIx{KGGodHXyJFMh\GG7czDifUBtfW2rbnXzZ4Vv[2VvYnHz[YQhS2WubGTpeIVzNUeubzDhd5NigSxiSVO1NEA:KDBwMEG1JO69VS5? MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTZ{N{eyOUc,Ojl4Mke3NlU9N2F-
DFCI114 NFqzOlNCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= NFuxSZI4OiCqcoO= MofWRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCGRlPJNVE1KGOnbHzzJIV5eHKnc4PpcochTU2OND3BUGshTzF{NknBJI12fGGwdDDh[pRmeiB5MjDodpMh[nliQ3XscHRqfGW{LVfsc{BNfW2rbnXzZ4VvfCCFZXzsJHZq[WKrbHn0fUBCe3OjeTygSWM2OCB;IECuNFE5KM7:TT6= Mnz6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3NkiyPFkoRjJ4NU[4Nlg6RC:jPh?=
HCC78 MorJR5l1d3SxeHnjbZR6KGG|c3H5 NV\RWYUyPzJiaILz NUT2ZWFuS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hUEOFN{igZ4VtdHNiaHHyZo9zcW6pIGPMR|M1STJvUl;TNUBie3Onc4Pl[EBieyC{ZXT1Z5Rqd25iaX6gZ4VtdCCycn;sbYZmemG2aX;uJIFnfGW{IEeyJIhzeyCkeTDNWHQh[XO|YYmsJGlEPTBiPTCwMlAyQCEQvF2u NVnT[4t1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMke0O|Q6OjVpPkK3OFc1QTJ3PD;hQi=>
KARPAS299 M3z1e2N6fG:2b4jpZ4l1gSCjc4PhfS=> M3XCb|IhfG9iMzDkZZl{ M4fp[mN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGtCWlCDU{K5PUBk\WyuczDh[pRmeiB{IITvJFMh\GG7czDifUBtfWOrZnXyZZNmKHKncH;yeIVzKGenbnWgZZN{[XluIFnDOVAhRSByLkCyNlgh|ryPLh?= NHyzcoM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e0NlI2Oid-MkO3OFIzPTJ:L3G+
KARPAS299 MY\DfZRwfG:6aXPpeJkh[XO|YYm= MnLMR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gT2FTWEGVMkm5JINmdGy|IHX4dJJme3OrbnegUnBONUGOSzDmeZNqd25iZ3Xu[UBie3Onc4Pl[EBieyCpcn;3eIghcW6qaXLpeIlwdixiSVO1NEA:KDBwMEKyPEDPxE1w MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzh|N{e5O{c,OjN6M{e3PVc9N2F-
NCI-H3122 MoX4SpVv[3Srb36gZZN{[Xl? M3;yZ|czKGi{cx?= MV;Jcohq[mm2aX;uJI9nKEWPTESg[pV{\WRiQVzLJIlvKGi3bXHuJG5EUS2KM{GyNkBk\WyuczDhd5Nme3OnZDDhd{Bk\WyuIHfyc5d1cCCrbnjpZol1cW:wIH3lZZN2emWmIHHmeIVzKDd{IHjyd{BjgSCVUlKgZZN{[XluIFPDOVAhRSByLkCyOUDPxE1w NX7hZ|BtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMke5NVUyPjlpPkK3PVE2OTZ7PD;hQi=>
BAF3 M37tUGZ2dmO2aX;uJIF{e2G7 MmnGNkB1dyB|IHThfZM> Mn;STY5pcWKrdHnvckBw\iCQUF2t[pV{\WRiQVzLJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW|c3XkJIlvKG2xdYPlJGJCTjNiY3XscJMh[W[2ZYKgNkB1dyB|IHThfZMh[nlibIXjbYZmemG|ZTDy[ZBwenSncjDn[Y5mKGG|c3H5MEBKSzVyIE2gNE4xOjZizszNMi=> NUnlWVFVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3OFIzPTJpPkKzO|QzOjV{PD;hQi=>
BA/F3 NFP0PHZEgXSxdH;4bYNqfHliYYPzZZk> MXjDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRU9HOyClZXzsd{BmgHC{ZYPzbY5oKE6STT3BUGsh\nW|aX;uJIdmdmViYYPz[ZN{\WRiYYOg[5Jwf3SqIHnubIljcXSrb36sJGlEPTBiPTCwMlAzPiEQvF2u NIfnUmk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{izO|c6Pyd-MkO4N|c4QTd:L3G+
KARPAS299 Ml74RY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? MXi3NkBpenN? NX3mNmszSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDLRXJRSVN{OUmgZ4VtdHNiaHHyZo9zcW6pIF7QUU1CVEtiYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NEA:KDBwMEK2JO69VS5? M4m3cFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7MUe0PFA6Lz5{OUG3OFgxQTxxYU6=
NCI-H2228 NEPKNo1CdnSrcILvcIln\XKjdHn2[UBie3OjeR?= NFTET404OiCqcoO= MkO0RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCQQ1mtTFIzOjhiY3XscJMhcGG{Yn;ybY5oKEWPTEStRWxMKGGodHXyJFczKGi{czDifUBOXFRiYYPzZZktKEmFNUCgQUAxNjB{NjFOwG0v Mn:4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB{MkOxNlAoRjNyMkKzNVIxRC:jPh?=
KARPAS299 MXzDfZRwfG:6aXPpeJkh[XO|YYm= MX63NkBpenN? M1;BfGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGtCWlCDU{K5PUBk\WyuczDoZZJjd3KrbnegUnBONUGOSzDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5iY3XscEBxem:uaX\ldoF1cW:wIHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVAhRSByLkCyO{DPxE1w MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzR5NEmyOUc,Ojd2N{S5NlU9N2F-
Ba/F3 MmXESpVv[3Srb36gZZN{[Xl? Mlz6O|IhcHK| MWfJcohq[mm2aX;uJI9nKEWPTEStRWxMKFNzMkC2XUBufXSjboSgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO|ZXSgbY4hdW:3c3WgRoEwTjNiY3XscJMh[XO|ZYPz[YQh[XNiY3XscEB3cWGkaXzpeJkh[W[2ZYKgO|IhcHK|IHL5JG1VWyCjc4PhfUwhUUN3MDC9JFAvODN|IN88UU4> NYHzNY16RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1OlgzQDlpPkK2OVY5Ojh7PD;hQi=>
NCI-H3122 Mn7jRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? Mnz2RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDD3bYxlKHS7cHWgbJVu[W5iTlPJMWg{OTJ{IHPlcIx{NCCFQ{WwJF0hOC5yM{ig{txONg>? MorpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ{M{W5OFUoRjJ4MkO1PVQ2RC:jPh?=
NCI-H3122 M3SyU2Z2dmO2aX;uJIF{e2G7 NYjLZlUyPzJiaILz MlvrTY5pcWKrdHnvckBw\iCHTVy0MWFNUyCrbjDoeY1idiCQQ1mtTFMyOjJiY3XscJMh[XO|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBk\WyuIIDyc4xq\mW{YYTpc44h[W[2ZYKgO|IhcHK|IHL5JHNTSiCjc4PhfUwhS0N3MDC9JFAvODN6IN88UU4> NG\meZk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkmyN|Y6PSd-Mk[5NlM3QTV:L3G+
NCI-H3122 MVPGeY5kfGmxbjDhd5NigQ>? MWC3NkBpenN? MoPNTY5pcWKrdHnvckBw\iCHTVy0MWFNUyCrbjDoeY1idiCQQ1mtTFMyOjJiY3XscJMh[XO|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBk\WyuIIDyc4xq\mW{YYTpc44h[W[2ZYKgO|IhcHK|IHL5JHNTSiCjc4PhfUwhS0N3MDC9JFAvODN6IN88UU4> MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjl{M{[5OUc,OjZ7MkO2PVU9N2F-
NCI-H3122 NX:4VI1jTnWwY4Tpc44h[XO|YYm= NETo[2Y4OiCqcoO= NULPN3puUW6qaXLpeIlwdiCxZjDFUWw1KG[3c3XkJGFNUyCrbjDoeY1idiCQQ1mtTFMyOjJiY3XscJMh[XO|ZYPz[YQh[XNiY3XscEBoem:5dHigbY5pcWKrdHnvckBi\nSncjC3NkBpenNiYomgV3JDKGG|c3H5MEBESzVyIE2gNE4xOzhizszNMi=> MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDN6NUWwOUc,Ojh|OEW1NFU9N2F-
BA/F3 MYTGeY5kfGmxbjDhd5NigQ>? MmjyTY5pcWKrdHnvckBw\iCDTFugLJVvc26xd36gc5Jq\2mwKTD0doFve2[nY4Tl[EBqdiCvb4Xz[UBDSS:IMzDj[YxteyxiSVO1NEA:KDBwMESwO{DPxE1w NIrLRmI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{izO|c6Pyd-MkO4N|c4QTd:L3G+
Ba/F3 NGfaNoFHfW6ldHnvckBie3OjeR?= MoqzO|IhcHK| MlnETY5pcWKrdHnvckBw\iC5aXzkJJR6eGViRV3MOE1CVEtiKIXub45wf25ib4Lp[4lvMSCneIDy[ZN{\WRiaX6gcY92e2ViQnGvSlMh[2WubIOgZZN{\XO|ZXSgZZMh[2WubDD2bYFjcWyrdImgZYZ1\XJiN{KgbJJ{KGK7IF3UV{Bie3OjeTygTWM2OCB;IECuNFQyKM7:TT6= MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjV4OEK4PUc,OjZ3NkiyPFk9N2F-
Ba/F3 NXm2Z49kTnWwY4Tpc44h[XO|YYm= MUm3NkBpenN? MYPJcohq[mm2aX;uJI9nKHerbHSgeJlx\SCHTVy0MWFNUyBqdX7rco94diCxcnnnbY4qKGW6cILld5Nm\CCrbjDtc5V{\SCEYT;GN{Bk\WyuczDhd5Nme3OnZDDhd{Bk\WyuII\pZYJqdGm2eTDh[pRmeiB5MjDodpMh[nliTWTTJIF{e2G7LDDJR|UxKD1iMD6wOFEh|ryPLh?= MkTrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3NkiyPFkoRjJ4NU[4Nlg6RC:jPh?=
KARPAS299 NHvmUmVCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MUO3NkBpenN? MlfaRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCNQWLQRXMzQTliY3XscJMhcGG{Yn;ybY5oKE6STT3BUGsh[W[2ZYKgO|IhcHK|IHL5JG1VXCCjc4PhfUwhUUN3MDC9JFAvODRzIN88UU4> M3q0eFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMkKzNVIxLz5|MEKyN|EzODxxYU6=
BAF3 Mn7HRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? Mn\BO|IhcHK| MWjBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IH3veZNmKEKDRkOgZ4VtdHNiaHHyZo9zcW6pIFXNUFQuSUyNIFyxNVk3VSCvdYThcpQh[W[2ZYKgO|IhcHK|IHL5JHNTSiCxcjDDR2s5KGG|c3H5MEBKSzVyIE2gNE4xPTR7IN88UU4> M2TpOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7Mki4PVQxLz5{OUK4PFk1ODxxYU6=
Ba/F3 MXnGeY5kfGmxbjDhd5NigQ>? MUW3NkBpenN? NXPTSmVJUW6qaXLpeIlwdiCxZjDFUWw1NUGOSzDHNVI3QUFibYX0ZY51KCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIH3veZNmKEKjL1[zJINmdGy|IHHzd4V{e2WmIHHzJINmdGxidnnhZoltcXS7IHHmeIVzKDd{IHjyd{BjgSCPVGOgZZN{[XluIFnDOVAhRSByLkC1O{DPxE1w MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjV4OEK4PUc,OjZ3NkiyPFk9N2F-
HCC78 NHv2colCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MlHiO|IhcHK| MVfBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEiFQ{e4JINmdGy|IHjhdoJwemmwZzDTUGM{PEF{LWLPV|Eh[W[2ZYKgO|IhcHK|IHL5JG1VXCCjc4PhfUwhUUN3MDC9JFAvODV6IN88UU4> MojoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjlzN{S4NFkoRjJ7MUe0PFA6RC:jPh?=
HCC78 MWLBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? MY[3NkBpenN? MW\BcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEiFQ{e4JINmdGy|IHjhdoJwemmwZzDTUGM{PEF{LWLPV|Eh[W[2ZYKgO|IhcHK|IHL5JG1VXCCjc4PhfUwhUUN3MDC9JFAvODV6IN88UU4> M3;ySVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMkKzNVIxLz5|MEKyN|EzODxxYU6=
Ba/F3 MmCwSpVv[3Srb36gZZN{[Xl? MVu3NkBpenN? MYXJcohq[mm2aX;uJI9nKEWPTEStRWxMKExzMUm2UUBufXSjboSgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO|ZXSgbY4hdW:3c3WgRoEwTjNiY3XscJMh[XO|ZYPz[YQh[XNiY3XscEB3cWGkaXzpeJkh[W[2ZYKgO|IhcHK|IHL5JG1VWyCjc4PhfUwhUUN3MDC9JFAvODZ2IN88UU4> NGPHNoQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkW2PFI5QSd-Mk[1OlgzQDl:L3G+
DFCI76 NHLpWlNCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MV:3NkBpenN? NF7YcoRCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFTGR2k4PiClZXzsd{BmgHC{ZYPzbY5oKEWPTEStRWxMKExzMUWyVkBufXSjboSgZYZ1\XJiN{KgbJJ{KGK7IFPlcIxVcXSncj3HcI8hVHWvaX7ld4NmdnRiQ3XscEBXcWGkaXzpeJkhSXO|YYmsJGVEPTBiPTCwMlA4OiEQvF2u MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjV4OEK4PUc,OjZ3NkiyPFk9N2F-
BAF3 NFjSZnlCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= NXnNdmIzSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBud3W|ZTDCRWY{KGOnbHzzJIV5eHKnc4PpcochSUyNIFyxNVk3VSCvdYThcpQtKEOFNUCgQUAxNjB5NTFOwG0v M2PtN|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MkO1PVQ2Lz5{NkKzOVk1PTxxYU6=
BA/F3 NVvWc5UyTnWwY4Tpc44h[XO|YYm= MU[3NkBpenN? MmjiTY5pcWKrdHnvckBw\iCDTFugUFEyQT[PIH31eIFvfCCrbjDtc5V{\SCEQT;GN{Bk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIHPlcIwheHKxbHnm[ZJifGmxbjDh[pRmeiB5MjDodpMh[nliV2PUNUBie3OjeTygR2M2OCB;IECuNFc2KM7:TT6= Ml[yQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ7MkO2PVUoRjJ4OUKzOlk2RC:jPh?=
BA/F3 MUfGeY5kfGmxbjDhd5NigQ>? NGHG[mU4OiCqcoO= Mk\GTY5pcWKrdHnvckBw\iCHTVy0JIZ2e2WmIFHMT{BNOTF7Nl2gcZV1[W62IDj1cotvd3ewIH;ybYdqdiliZYjwdoV{e2WmIHnuJI1wfXOnIFLBM2Y{KGOnbHzzJIF{e2W|c3XkJIF{KGOnbHyg[5Jwf3SqIHnubIljcXSrb36gcYVie3W{ZXSgZYZ1\XJiN{KgbJJ{KGK7IGPSRkBie3OjeTygR2M2OCB;IECuNFc2KM7:TT6= MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzlzNUG2PUc,Ojd7MUWxOlk9N2F-
BA/F3 MWfGeY5kfGmxbjDhd5NigQ>? M4K0eFczKGi{cx?= M4XJSmlvcGmkaYTpc44hd2ZiRV3MOEBnfXOnZDDBUGshMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5ibX;1d4UhSkFxRkOgZ4VtdHNiYYPz[ZN{\WRiYYOgZ4VtdCCpcn;3eIghcW6qaXLpeIlwdiCvZXHzeZJm\CCjZoTldkA4OiCqcoOgZpkhW1KEIHHzd4F6NCCFQ{WwJF0hOC5yN{Wg{txONg>? M1jmcFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5OUG1NVY6Lz5{N{mxOVE3QTxxYU6=
BAF3 M2\XRmZ2dmO2aX;uJIF{e2G7 Mk[wO|IhcHK| NXLrTmFtUW6qaXLpeIlwdiCxZjDBUGshVDFzOU\NJI12fGGwdDCoeY5sdm:5bjDvdolocW5rIHX4dJJme3OnZDDpckBud3W|ZTDCRWY{KGOnbHzzJIF{e2W|c3XkJIF{KGOnbHyg[5Jwf3SqIHnubIljcXSrb36gZYZ1\XJiN{KgbJJ{KGK7IGfTWE0yKGG|c3H5MEBESzVyIE2gNE4xPzVizszNMi=> MlmwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh|OEW1NFUoRjJ6M{i1OVA2RC:jPh?=
KARPAS299 M2K2emFvfGmycn;sbYZmemG2aY\lJIF{e2G7 M{HZUVczKGi{cx?= NFraVZBCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFvBVnBCWzJ7OTDj[YxteyCqYYLic5JqdmdiTmDNMWFNUyCjZoTldkA4OiCqcoOgZpkhW1KEIH;yJGNEUzhiYYPzZZktKEmFNUCgQUAxNjB6NDFOwG0v MlS3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl{OEi5OFAoRjJ7Mki4PVQxRC:jPh?=
SMS-KCNR NUezR4ZSSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NEDD[5o4OiCqcoO= M3v1NGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iU13TMWtEVlJiY3XscJMh\XiycnXzd4lv\yCHTVy0MWFNUyCUMUK3OXEhdXW2YX70JIFnfGW{IEeyJIhzeyCkeTDD[YxtXGm2ZYKtS4xwKEy3bXnu[ZNk\W62IFPlcIwhXmmjYnnsbZR6KEG|c3H5MEBGSzVyIE2gNE4xQTJizszNMi=> Ml23QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3NkiyPFkoRjJ4NU[4Nlg6RC:jPh?=
NCI-H3122 MVnBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? NITzUnQ4OiCqcoO= NITMZ25CdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF7DTU1JOzF{MjDj[YxteyCjZoTldkA4OiCqcoOgZpkhW1KEIH;yJGNEUzhiYYPzZZktKEmFNUCgQUAxNjB7NjFOwG0v NIrmc3g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUK4PFk1OCd-MkmyPFg6PDB:L3G+
NCI-H2228 NVqxbXlMSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NGHhfXQ4OiCqcoO= M174OGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTlPJMWgzOjJ6IHPlcIx{KGijcnLvdolv\yCHTVy0MWFNUyCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwJF0hOC5yOUmg{txONg>? M1nUSlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7MUe0PFA6Lz5{OUG3OFgxQTxxYU6=
Ba/F3 MVnGeY5kfGmxbjDhd5NigQ>? M4DibFczKGi{cx?= M3;TNmlvcGmkaYTpc44hd2ZiRV3MOE1CVEtiRkGxO|RNKG23dHHueEApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCvb4Xz[UBD[S:IMzDj[YxteyCjc4Pld5Nm\CCjczDj[YxtKH[rYXLpcIl1gSCjZoTldkA4OiCqcoOgZpkhVVSVIHHzd4F6NCCLQ{WwJF0hOC5zMEGg{txONg>? NXXrTIxiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1OlgzQDlpPkK2OVY5Ojh7PD;hQi=>
NCI-H2228 Mk\2R5l1d3SxeHnjbZR6KGG|c3H5 M3S1XlczKGi{cx?= M1nTd2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJG5EUS2KMkKyPEBk\WyuczDhd5Nme3OnZDDhd{Bk\WyuII\pZYJqdGm2eTDh[pRmeiB5MjDodpMh[nliTWTTJIF{e2G7LDDJR|UxKD1iMD6xNFI3KM7:TT6= M2\tXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkS0OlcyLz5{NU[0OFY4OTxxYU6=
LAN5 MVjBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? MUS3NkBpenN? MmiwRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCOQV61JINmdGy|IHX4dJJme3OrbnegSW1NPC2DTFugVlEzPzWTIH31eIFvfCCjZoTldkA4OiCqcoOgZpkhS2WubGTpeIVzNUeubzDMeY1qdmW|Y3XueEBE\WyuIG\pZYJqdGm2eTDBd5NigSxiRVO1NEA:KDBwMUKyJO69VS5? MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjV4OEK4PUc,OjZ3NkiyPFk9N2F-
SU-DHL1 MUPBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? M2jLXFczKGi{cx?= NVXlcXl6SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDTWU1FUExzIHPlcIx{KGijcnLvdolv\yCQUF2tRWxMKGGodHXyJFczKGi{czDifUBUWkJib4KgR2NMQCCjc4PhfUwhUUN3MDC9JFAvOTJ{IN88UU4> MnjBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl{OEi5OFAoRjJ7Mki4PVQxRC:jPh?=
Kelly M3O2cWFvfGmycn;sbYZmemG2aY\lJIF{e2G7 NWfCc25LPzJiaILz NVflXop7SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDL[YxtgSClZXzsd{BmgHC{ZYPzbY5oKEWPTEStRWxMKEZzMUe0UEBufXSjboSgZYZ1\XJiN{KgbJJ{KGK7IFPlcIxVcXSncj3HcI8hVHWvaX7ld4NmdnRiQ3XscEBXcWGkaXzpeJkhSXO|YYmsJGVEPTBiPTCwMlE1OiEQvF2u M1PX[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NU[4Nlg6Lz5{NkW2PFI5QTxxYU6=
Ba/F3 MYnGeY5kfGmxbjDhd5NigQ>? MkH0O|IhcHK| NV;rOIVDUW6qaXLpeIlwdiCxZjDFUWw1NUGOSzDDNVE2PllibYX0ZY51KCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIH3veZNmKEKjL1[zJINmdGy|IHHzd4V{e2WmIHHzJINmdGxidnnhZoltcXS7IHHmeIVzKDd{IHjyd{BjgSCPVGOgZZN{[XluIFnDOVAhRSByLkG2OEDPxE1w NYjBSIg4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1OlgzQDlpPkK2OVY5Ojh7PD;hQi=>
SH-SY5Y NXPweWJISW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NVLZc5VwPzJiaILz MWPBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKFOKLWPZOXkh[2WubIOg[ZhxemW|c3nu[{BGVUx2LVHMT{BHOTF5NFygcZV1[W62IHHmeIVzKDd{IHjyd{BjgSCFZXzsWIl1\XJvR3zvJGx2dWmwZYPj[Y51KEOnbHygWoli[mmuaYT5JGF{e2G7LDDFR|UxKD1iMD6xPFYh|ryPLh?= NHToV4o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkW2PFI5QSd-Mk[1OlgzQDl:L3G+
BAF3 M2PEbWFvfGmycn;sbYZmemG2aY\lJIF{e2G7 MoXTO|IhcHK| NXn3WHg{SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBud3W|ZTDCRWY{KGOnbHzzJIhiemKxcnnu[{BETDd2LWLPV|Eh[W[2ZYKgO|IhcHK|IHL5JHNTSiCxcjDDR2s5KGG|c3H5MEBKSzVyIE2gNE4zOzRizszNMi=> NWLFOoFnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmyPFg6PDBpPkK5Nlg5QTRyPD;hQi=>
SK-N-SH NFrUU5lCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= NV;xfVUzPzJiaILz NHP1VGlCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGPLMW4uW0hiY3XscJMh\XiycnXzd4lv\yCHTVy0MWFNUyCIMUG3OGwhdXW2YX70JIFnfGW{IEeyJIhzeyCkeTDD[YxtXGm2ZYKtS4xwKEy3bXnu[ZNk\W62IFPlcIwhXmmjYnnsbZR6KEG|c3H5MEBGSzVyIE2gNE4{ODNizszNMi=> NGrNcZQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkW2PFI5QSd-Mk[1OlgzQDl:L3G+
BAF3 NGX1eVZHfW6ldHnvckBie3OjeR?= NEj3NlMzKHSxIEOg[IF6ew>? MV3Jcohq[mm2aX;uJI9nKFSHTD3meZNm\CCrboP1cIlvKHKnY3XweI9zKCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIH3veZNmKEKDRkOgZ4VtdHNiYX\0[ZIhOiC2bzCzJIRigXNiYomgcJVkcW[ncnHz[UBz\XCxcoTldkBo\W6nIHHzd4F6NCCLQ{WwJF0hOC5|MUm1JO69VS5? NX7BeoE{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3OFIzPTJpPkKzO|QzOjV{PD;hQi=>
BA/F3 MYDDfZRwfG:6aXPpeJkh[XO|YYm= MWPDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRU9HOyClZXzsd{B1emGwc3\lZ5Rm\CC5aYToJHRmdC2LboPSJIdmdmViYYPz[ZN{\WRiYYOg[5Jwf3SqIHnubIljcXSrb36sJGlEPTBiPTCwMlMzKM7:TT6= MnnLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN6M{e3PVcoRjJ|OEO3O|k4RC:jPh?=
SK-N-FI NIPCSHNCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MYm3NkBpenN? NXrBWHZOSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDTT{1PNU[LIHPlcIx{KGW6cILld5Nqdmdid3ns[EB1gXCnIFXNUFQuSUyNIHHmeIVzKDd{IHjyd{BjgSCFZXzsWIl1\XJvR3zvJGx2dWmwZYPj[Y51KEOnbHygWoli[mmuaYT5JGF{e2G7LDDFR|UxKD1iMD6zOFkh|ryPLh?= MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjV4OEK4PUc,OjZ3NkiyPFk9N2F-
CHLA20 Ml:0RY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? MmHYO|IhcHK| NH;lV4dCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFPIUGEzOCClZXzsd{BmgHC{ZYPzbY5oKEWPTEStRWxMKFJzMke1VUBufXSjboSgZYZ1\XJiN{KgbJJ{KGK7IFPlcIxVcXSncj3HcI8hVHWvaX7ld4NmdnRiQ3XscEBXcWGkaXzpeJkhSXO|YYmsJGVEPTBiPTCwMlM3OyEQvF2u NGKyNmw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkW2PFI5QSd-Mk[1OlgzQDl:L3G+
Ba/F3 MVXGeY5kfGmxbjDhd5NigQ>? MVW3NkBpenN? M{nhUGlvcGmkaYTpc44hd2ZiRV3MOE1CVEtiR{GyNFJTKG23dHHueEApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCvb4Xz[UBD[S:IMzDj[YxteyCjc4Pld5Nm\CCjczDj[YxtKH[rYXLpcIl1gSCjZoTldkA4OiCqcoOgZpkhVVSVIHHzd4F6NCCLQ{WwJF0hOC52NESg{txONg>? M2HN[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NU[4Nlg6Lz5{NkW2PFI5QTxxYU6=
LAN1 M1;BVGFvfGmycn;sbYZmemG2aY\lJIF{e2G7 NFHKSFk4OiCqcoO= MXTBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEyDTkGgZ4VtdHNiZYjwdoV{e2mwZzDFUWw1NUGOSzDGNVE4PExibYX0ZY51KGGodHXyJFczKGi{czDifUBE\WyuVHn0[ZIuT2yxIFz1cYlv\XOlZX70JGNmdGxiVnnhZoltcXS7IFHzd4F6NCCHQ{WwJF0hOC53NEmg{txONg>? M33yT|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NU[4Nlg6Lz5{NkW2PFI5QTxxYU6=
SK-N-BE(2) M{nNbGFvfGmycn;sbYZmemG2aY\lJIF{e2G7 M3TFOlczKGi{cx?= M332U2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iU1utUk1DTSh{KTDj[YxteyCneIDy[ZN{cW6pIIfpcIQhfHmyZTDFUWw1NUGOSzDh[pRmeiB5MjDodpMh[nliQ3XscHRqfGW{LVfsc{BNfW2rbnXzZ4VvfCCFZXzsJHZq[WKrbHn0fUBCe3OjeTygSWM2OCB;IECuOVk{KM7:TT6= MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjV4OEK4PUc,OjZ3NkiyPFk9N2F-
Ba/F3 M4rKVGZ2dmO2aX;uJIF{e2G7 M4fRUVczKGi{cx?= NYiyOWl2UW6qaXLpeIlwdiCxZjDFUWw1NUGOSzCxNVUyXGmwczDteZRidnRiKIXub45wf25ib4Lp[4lvMSCneIDy[ZN{\WRiaX6gcY92e2ViQnGvSlMh[2WubIOgZZN{\XO|ZXSgZZMh[2WubDD2bYFjcWyrdImgZYZ1\XJiN{KgbJJ{KGK7IF3UV{Bie3OjeTygTWM2OCB;IECuOlY5KM7:TT6= NIL3eoE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkW2PFI5QSd-Mk[1OlgzQDl:L3G+
BAF3 MYXBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? M2q3XVczKGi{cx?= MmnjRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDtc5V{\SCEQV[zJINmdGy|IHjhdoJwemmwZzDFUWw1NUGOSzDHNVIxOlJibYX0ZY51KGGodHXyJFczKGi{czDifUBUWkJib4KgR2NMQCCjc4PhfUwhUUN3MDC9JFAvPzJ4IN88UU4> NUfiSWRmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmyPFg6PDBpPkK5Nlg5QTRyPD;hQi=>
Ba/F3 MlHvSpVv[3Srb36gZZN{[Xl? NWTlboxiPzJiaILz NI\JSnNKdmirYnn0bY9vKG:oIHj1cYFvKEWJRmKg[IVtOTlxVEe5NG0wSzd7N2OgcZV1[W62IHX4dJJme3OnZDDpckBud3W|ZTDCZU9HOyClZXzsd{Bie3Onc4Pl[EBieyClZXzsJIdzd3e2aDDpcohq[mm2aX;uJIFnfGW{IEeyJIhzeyCkeTDD[YxtXGm2ZYKtS4xwKGG|c3H5MEBIUTVyIE2gNE44QDB3IN88UU4> NFG2cYQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUGzOlQ3PSd-MkmxN|Y1PjV:L3G+
SK-N-AS M1XFcWFvfGmycn;sbYZmemG2aY\lJIF{e2G7 NYr5N2dmPzJiaILz MVvBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKFONLV6tRXMh[2WubIOg[ZhxemW|c3nu[{B4cWymIIT5dIUhTU2OND3BUGsh[W[2ZYKgO|IhcHK|IHL5JGNmdGyWaYTldk1IdG9iTIXtbY5me2OnboSgR4VtdCCYaXHibYxqfHliQYPzZZktKEWFNUCgQUAyNjB2NTFOwG0v NYnZOXBlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1OlgzQDlpPkK2OVY5Ojh7PD;hQi=>
BAF3 M2f1NGN6fG:2b4jpZ4l1gSCjc4PhfS=> NE[yUI4zKHSxIEOg[IF6ew>? M3S3fGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KG2xdYPlJGJCTjNiY3XscJMh[W[2ZYKgNkB1dyB|IHThfZMh[nlibIXjbYZmemG|ZTDy[ZBwenSncjDn[Y5mKGG|c3H5MEBKSzVyIE2gNk41PzdizszNMi=> MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd2MkK1Nkc,OjN5NEKyOVI9N2F-
Ba/F3 NFrGR|lHfW6ldHnvckBie3OjeR?= MXG3NkBpenN? MnL2TY5pcWKrdHnvckBw\iCHTVy0MWFNUyCOMUG1NnIhdXW2YX70JEh2dmuwb4fuJI9zcWerbjmg[ZhxemW|c3XkJIlvKG2xdYPlJGJiN0Z|IHPlcIx{KGG|c3Xzd4VlKGG|IHPlcIwhfmmjYnnsbZR6KGGodHXyJFczKGi{czDifUBOXFNiYYPzZZktKEmFNUCgQUAzNjd2NzFOwG0v M3LGSlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NU[4Nlg6Lz5{NkW2PFI5QTxxYU6=
BA/F3 MmflR5l1d3SxeHnjbZR6KGG|c3H5 MVW3NkBpenN? MVvDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRU9HOyClZXzsd{Bie3Onc4Pl[EBieyClZXzsJJZq[WKrbHn0fUBi\nSncjC3NkBpenNiYomgUXRUKGG|c3H5MEBKSzVyIE2gOU42OTJizszNMi=> MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjV4OEK4PUc,OjZ3NkiyPFk9N2F-
KARPAS299 MVLBdI9xfG:|aYOgZZN{[Xl? NIrIVI03OCCwTR?= Mk\GNlQhcHK| M4rZcmlv\HWldHnvckBw\iCjcH;weI9{cXNiaX6gbJVu[W5iS1HSVGFUOjl7IHPlcIx{KGijcnLvdolv\yCQUF2tRWxMKGG2IE[wJI5OKGGodHXyJFI1KGi{czDifUBi[3KrZHnu[UBwemGwZ3Wv[ZRpcWSrdX2gZpJwdWmmZTDzeIFqdmmwZzDiZZNm\CCobIXvdoV{[2WwY3WgcYlkem:|Y3;wbYMhdWW2aH;k Ml;YQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjlzN{S4NFkoRjJ7MUe0PFA6RC:jPh?=
SU-DHL1 NGPuR5VHfW6ldHnvckBie3OjeR?= MV2yNEB1dyB{MECgcm0> M{jyOlEhcHJ? MlTCTY5pcWKrdHnvckBw\iCDTFugbY4hcHWvYX6gV3UuTEiOMTDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gbY4hW1SDVEOgdIhwe3Cqb4L5cIF1cW:wIHH0JHk4ODVicnXzbYR2\SCjdDCyNEB1dyB{MECgcm0h[W[2ZYKgNUBpeiCkeTDX[ZN1\XKwIHLsc5Qh[W6jbInzbZM> NFi3O2o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUK4PFk1OCd-MkmyPFg6PDB:L3G+
SU-DHL1 NWjZ[VB6TnWwY4Tpc44h[XO|YYm= MnuzNlAhfG9iMkCwJI5O M3:ySlEhcHJ? NUHDSpZ2UW6qaXLpeIlwdiCxZjDBUGsheGixc4Doc5J6dGG2aX;uJIF1KFlzMke4JJJme2mmdXWgbY4hcHWvYX6gV3UuTEiOMTDj[YxteyCjdDCyNEB1dyB{MECgcm0h[W[2ZYKgNUBpeiCkeTDX[ZN1\XKwIHLsc5Qh[W6jbInzbZM> M1\Vc|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7Mki4PVQxLz5{OUK4PFk1ODxxYU6=
NCI-H3122 M4W0dGZ2dmO2aX;uJIF{e2G7 NUn0WlVWOjBidH:gNlAxKG6P MoTvNUBpeg>? M4rudGlvcGmkaYTpc44hd2ZiQVzLJIlvKGi3bXHuJG5EUS2KM{GyNkBk\WyuczDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5iRWLLJJBpd3OyaH;yfYxifGmxbjDheEBVOjB{Lz;ZNlA1KHKnc3nkeYV{KGG2IEKwJJRwKDJyMDDuUUBi\nSncjCxJIhzKGK7IGfld5Rmem5iYnzveEBidmGueYPpdy=> NVX0SlJRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmyPFg6PDBpPkK5Nlg5QTRyPD;hQi=>
NCI-H3122 NVHtV5NlTnWwY4Tpc44h[XO|YYm= NYTrXG5kOjBidH:gNlAxKG6P M1n3cVEhcHJ? M1vTUGlvcGmkaYTpc44hd2ZiQVzLJIlvKGi3bXHuJG5EUS2KM{GyNkBk\WyuczDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5iQXv0JJBpd3OyaH;yfYxifGmxbjDheEBUPDd|IILld4llfWViYYSgNlAhfG9iMkCwJI5OKGGodHXyJFEhcHJiYomgW4V{fGW{bjDicI91KGGwYXz5d4l{ M2PJdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7Mki4PVQxLz5{OUK4PFk1ODxxYU6=
SU-DHL1 NYP0bHZuTnWwY4Tpc44h[XO|YYm= NU\GbGxWOjBidH:gNlAxKG6P MUCxJIhz MnXyTY5pcWKrdHnvckBw\iCDTFugbY4hcHWvYX6gV3UuTEiOMTDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gbY4hSWu2IIDoc5NxcG:{eXzheIlwdiCjdDDTOFc{KHKnc3nkeYUh[XRiMkCgeI8hOjByIH7NJIFnfGW{IEGgbJIh[nliV3XzeIVzdiCkbH;0JIFv[Wy7c3nz NFrjdFU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUK4PFk1OCd-MkmyPFg6PDB:L3G+
SU-DHL1 M{DxR2Z2dmO2aX;uJIF{e2G7 NVWzTHVNOjBidH:gNlAxKG6P MmDyNUBpeg>? MVHJcohq[mm2aX;uJI9nKEGOSzDpckBpfW2jbjDTWU1FUExzIHPlcIx{KGG|c3Xzd4VlKGG|IILl[JVkfGmxbjDpckBGWkticHjvd5Bpd3K7bHH0bY9vKGG2IGSyNFIwN1l{MESgdoV{cWS3ZYOgZZQhOjBidH:gNlAxKG6PIHHmeIVzKDFiaIKgZpkhX2W|dHXyckBjdG:2IHHuZYx6e2m| NU\rd5d5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmyPFg6PDBpPkK5Nlg5QTRyPD;hQi=>
NCI-H3122 MYTGeY5kfGmxbjDhd5NigQ>? NUT0VnB{OjBidH:gNlAxKG6P NUXSTYt[OSCqch?= MVHJcohq[mm2aX;uJI9nKEGOSzDwbI9{eGixconsZZRqd25iYYSgXVEzPzhicnXzbYR2\SCrbjDoeY1idiCQQ1mtTFMyOjJiY3XscJMh[XRiMkCgeI8hOjByIH7NJIFnfGW{IEGgbJIh[nliV3XzeIVzdiCkbH;0JIFv[Wy7c3nz MnXVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl{OEi5OFAoRjJ7Mki4PVQxRC:jPh?=
NCI-H3122 MlvuSpVv[3Srb36gZZN{[Xl? NUniTJJLOjBidH:gNlAxKG6P NHrFSWgyKGi{ MnTVTY5pcWKrdHnvckBw\iCDTFugbY4hcHWvYX6gUmNKNUh|MUKyJINmdGy|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiCVVFHUN{BxcG:|cHjvdplt[XSrb36gZZQhYTdyNTDy[ZNq\HWnIHH0JFIxKHSxIEKwNEBvVSCjZoTldkAyKGi{IHL5JHdme3Sncn6gZoxwfCCjbnHsfZNqew>? MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTJ6OEm0NEc,Ojl{OEi5OFA9N2F-
SU-DHL1 Mn3ISpVv[3Srb36gZZN{[Xl? M2jEW|MxKG6P MlfkNVYhcHK| MUDJcohq[mm2aX;uJI9nKEGOSzDheZRweGixc4Doc5J6dGG2aX;uJIF1KFlzNUC3JJJme2mmdXWgbY4hcHWvYX6gV3UuTEiOMTDj[YxteyCjdDCzNEBvVSCjZoTldkAyPiCqcoOgZpkhX2W|dHXyckBjdG:2IHHuZYx6e2m| NYHBTnp{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm2Nlc4OjVpPkK5OlI4PzJ3PD;hQi=>
SU-DHL1 NX;3WWJ7TnWwY4Tpc44h[XO|YYm= NVP3R|YxOzBibl2= MkSxNVYhcHK| NFSxRoJKdmirYnn0bY9vKG:oIFHMT{BqdiCqdX3hckBUXS2GSFyxJINmdGy|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiCVVFHUN{BxcG:|cHjvdplt[XSrb36gZZQhYTdyNTDy[ZNq\HWnIHH0JFMxKG6PIHHmeIVzKDF4IHjyd{BjgSCZZYP0[ZJvKGKub4SgZY5idHm|aYO= Mne2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl4Mke3NlUoRjJ7NkK3O|I2RC:jPh?=
NCI-H3122 MkTJSpVv[3Srb36gZZN{[Xl? MVW1NEB1dyB{NUCgcm0> NGjNVnoyPiCqcoO= MXjJcoR2[3Srb36gc4YhSUyNIHTl[5Ji\GG2aX;uJIlvKGi3bXHuJG5EUS2KM{GyNkBk\WyuczDhd5Nme3OnZDDhd{Bl\WO{ZXHz[UBqdiCDTFugdIhwe3Cqb4L5cIF1cW:wIHH0JHkyPjB2IHH0JFUxKHSxIEK1NEBvVSCjZoTldkAyPiCqcoOgZpkhcW2vdX7vZoxwfCCvZYToc4Q> NF23N5o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OU[2NFk5PCd-Mkm2OlA6QDR:L3G+
SH-SY5Y NITwUVBCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MkTsO|IhcHK| Mmf4RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCVSD3TXVV[KGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDD[YxtXGm2ZYKtS4xwKGy3bXnu[ZNk\W62IHPlcIwhfmmjYnnsbZR6KGG|c3H5 NETEWHk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OU[2NFk5PCd-Mkm2OlA6QDR:L3G+
CHLA20 MVfBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? MYS3NkBpenN? Mn7lRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCFSFzBNlAh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IFPlcIxVcXSncj3HcI8hdHWvaX7ld4NmdnRiY3XscEB3cWGkaXzpeJkh[XO|YYm= MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTZ4MEm4OEc,Ojl4NkC5PFQ9N2F-
SH-SY5Y NY\QXHI3SW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= MUW3NkBpenN? M{nxdmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iU1itV3k2YSClZXzsd{Bi\nSncjC3NkBpenNiaX6gdJJme2WwY3Wgc4YhSUKFQkGgbY5pcWKrdH;yJJRiemmzdXnkZZIh[nliQ3XscHRqfGW{LVfsc{BtfW2rbnXzZ4VvfCClZXzsJJZq[WKrbHn0fUBie3OjeR?= MojvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl4NkC5PFQoRjJ7Nk[wPVg1RC:jPh?=
KARPAS299 M1nJcWZ2dmO2aX;uJIF{e2G7 NFHtOow2OCC2bzCyOVAhdk1? NIf4RXcyPiCqcoO= MkHWTY5lfWO2aX;uJI9nKEGOSzDk[Ydz[WSjdHnvckBqdiCqdX3hckBMSVKSQWOyPVkh[2WubIOgZZN{\XO|ZXSgZZMh\GWlcnXhd4UhcW5iQVzLJJBpd3OyaH;yfYxifGmxbjDheEB[OTZyNDDheEA2OCC2bzCyOVAhdk1iYX\0[ZIhOTZiaILzJIJ6KGmvbYXuc4Jtd3RibXX0bI9l NInQNYs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OU[2NFk5PCd-Mkm2OlA6QDR:L3G+
CHLA20 NFrBOnhCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MnKwO|IhcHK| NFu2T5FCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFPIUGEzOCClZXzsd{Bi\nSncjC3NkBpenNiaX6gdJJme2WwY3Wgc4YhSUKFQkGgbY5pcWKrdH;yJJRiemmzdXnkZZIh[nliQ3XscHRqfGW{LVfsc{BtfW2rbnXzZ4VvfCClZXzsJJZq[WKrbHn0fUBie3OjeR?= NUn0SYtDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm2OlA6QDRpPkK5OlYxQTh2PD;hQi=>
NCI-H3122 Mmm3RY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? Mn7qO|IhcHK| M1vQTmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTlPJMWg{OTJ{IHPlcIx{KGGodHXyJFczKGi{czDifUBE\WyuVHn0[ZIuT2yxIHz1cYlv\XOlZX70JINmdGxidnnhZoltcXS7IHHzd4F6 M1P0U|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7Nk[wPVg1Lz5{OU[2NFk5PDxxYU6=
KARPAS299 Mo[4RY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? M2LGc|czKGi{cx?= MnXHRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCNQWLQRXMzQTliY3XscJMh[W[2ZYKgO|IhcHK|IHL5JGNmdGyWaYTldk1IdG9ibIXtbY5me2OnboSgZ4VtdCC4aXHibYxqfHliYYPzZZk> M3PNNVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7Nk[wPVg1Lz5{OU[2NFk5PDxxYU6=
SU-DHL1 MY\BcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? MYi3NkBpenN? Mlm2RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCVVT3ETGwyKGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDD[YxtXGm2ZYKtS4xwKGy3bXnu[ZNk\W62IHPlcIwhfmmjYnnsbZR6KGG|c3H5 Ml7qQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl4NkC5PFQoRjJ7Nk[wPVg1RC:jPh?=
KARPAS299 MXLBdI9xfG:|aYOgZZN{[Xl? Ml7POVAhdk1? NGjtSVczPCCqcoO= NWDkcZJvUW6mdXP0bY9vKG:oIHHwc5B1d3OrczDpckBpfW2jbjDLRXJRSVN{OUmgZ4VtdHNiYYPz[ZN{\WRiYYOgeY5kdGWjcjDj[YxtKHOqcnnub4Fo\SCjdDC1NEBvVSCjZoTldkAzPCCqcoOgZpkhUG:nY3jzeEA{OzJ3ODDzeIFqdmmwZzDiZZNm\CCrbo\ldpRm\CCobIXvdoV{[2WwY3WgcYlkem:|Y3;wfS=> NH\MR4c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MEKyN|EzOCd-M{CyNlMyOjB:L3G+
KARPAS299 MXTBdI9xfG:|aYOgZZN{[Xl? MnfGOVAhdk1? MYiyOEBpenN? MlLTTY5lfWO2aX;uJI9nKGGyb4D0c5NqeyCrbjDoeY1idiCNQWLQRXMzQTliY3XscJMh[XO|ZYPz[YQh[XNibHH0[UBieG:ydH;0bYMh[2WubIOgZZQhPTBibl2gZYZ1\XJiMkSgbJJ{KGK7IFHPM2VDKGSxdXLs[UB{fGGrbnnu[{Bj[XOnZDDpcpZmenSnZDDmcJVwemW|Y3XuZ4UhdWmlcn;zZ49xgQ>? NUTDcolpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CyNlMyOjBpPkOwNlI{OTJyPD;hQi=>
KARPAS299 MWnBdI9xfG:|aYOgZZN{[Xl? NETOOIc2OCCwTR?= MXSyOEBpenN? NInVOHVKdmS3Y4Tpc44hd2ZiYYDvdJRwe2m|IHnuJIh2dWGwIFvBVnBCWzJ7OTDj[YxteyCjc4Pld5Nm\CCjczDmdoFodWWwdHH0bY9vKGG2IEWwJI5OKGGodHXyJFI1KGi{czDifUBJd2WlaIP0JFM{OjV6IIP0ZYlvcW6pIHLhd4VlKGmwdnXyeIVlKG[udX;y[ZNk\W6lZTDtbYNzd3Olb4D5 NWrzR2NGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CyNlMyOjBpPkOwNlI{OTJyPD;hQi=>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-ALK / ALK / p-AKT / AKT / p-ERK / ERK; 

PubMed: 28425916     


Inhibition of ALK autophosphorylation and downstream signaling by ceritinib, crizotinib and PF06463922 in NB-1 cells. Cells were harvested after treatment for 4 hr with the indicated compounds at different concentrations. Whole cell lysates were analyzed by Western blotting to detect the levels of ALK, AKT and ERK proteins and their phosphorylation.

pROS1 / ROS1 / pSTAT3 / STAT3 ; 

PubMed: 25351743     


Inhibition of phospho-ROS1 by various ALK inhibitors in Ba/F3 models. CD74-ROS1 expressing Ba/F3 cells were exposed to increasing concentrations of crizotinib, ceritinib, AP26113, or ASP3026 for 3 h. Cell lysates were immunoblotted to detect the indicated proteins.

28425916 25351743
Growth inhibition assay
Cell viability; 

PubMed: 29067644     


The effects of ceritinib treatment on cell viability in ARMS and ERMS cell lines. Cells were treated with 0-5 μM ceritinib for 72 h (Rh30, RD), 120 h (Rh41), or 144 h (Rh18, Aska) and cell viability was assessed. The y-axis represents relative cell viability compared to non-treated cells (control). Effects on cell viability were determined in triplicate. Values are presented as mean ± SD. Dotted line represents the IC50-value. The human synovial sarcoma cell line Aska with constitutive ALK phosphorylation was used as a positive control.

29067644
体内研究 LDK378 用于降低形成反应代谢的可能性,在肝微粒体几乎检测不到谷胱甘肽(GSH)加合物的水平(<1%)。LDK378具有相对良好的代谢稳定性,中度抑制CYP3A4(Midazolam底物)和抑制hERG。LDK378处理动物,与肝脏血流量相比,具有低的血浆清除率(小鼠,大鼠,狗和猴),处理小鼠,大鼠,狗和猴的口服生物利用度都在55%以上。LDK378 处理Karpas299 和H2228 大鼠移植瘤模型,抑制肿瘤生长,诱导肿瘤衰退,这种作用具有剂量依赖性,体重没有降低。LDK378处理小鼠,剂量高达100 mg/kg,对胰岛素水平或血浆葡萄糖的利用无影响。[1]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:[1]
- 合并

激酶分析:

所有激酶使用杆状病毒表达技术表达为组氨酸或GST标签的融合蛋白,除了在大肠杆菌中产生的未标记的ERK2。在LabChip迁移实验中测量激酶活性。实验在30°C下进行60分钟。在有或无LDK378存在时,通过线性进展曲线,获得LDK378对酶活性的作用效果。
细胞实验:[1]
- 合并
  • Cell lines: Ba/F3-NPM-ALK, Ba/F3-Tel-InsR, Ba/F3-WT, Karpas299 细胞
  • Concentrations: ~100 μM
  • Incubation Time: 2-3 天
  • Method: 表达荧光素酶的细胞与连续稀释的LDK378 或 DMSO 温育2-3天。荧光素酶的表达用来衡量细胞增殖/存活,使用Bright-Glo萤光素酶检测系统来评估。使用 XLFit软件获得 IC50值。
    (Only for Reference)
动物实验:[1]
- 合并
  • Animal Models: 携带 Karpas299/H2228肿瘤的 RNU裸鼠
  • Dosages: ~50 mg/kg
  • Administration: 口服饲喂
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 20 mg/mL warmed (35.83 mM)
Ethanol 3 mg/mL (5.37 mM)
Water Insoluble

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 558.14
化学式

C28H36ClN5O3S

CAS号 1032900-25-6
储存条件 粉状
溶于溶剂
别名 N/A

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系Selleck为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % ddH2O
计算重置

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02450903 Completed Drug: LDK378 Non-Small-Cell Lung Cancer Novartis Pharmaceuticals|Novartis August 21 2015 Phase 2
NCT02040870 Completed Drug: LDK378 Non-Small Cell Lung Cancer Novartis Pharmaceuticals|Novartis March 7 2014 Phase 1|Phase 2
NCT01950481 Completed Drug: LDK378 Normal Hepatic Function|Impaired Hepatic Function Novartis Pharmaceuticals|Novartis January 2014 Phase 1
NCT01772797 Completed Drug: LDK378|Drug: AUY922 Anaplastic Lymphoma Kinase (ALK)|Non-small Cell Lung Cancer Novartis Pharmaceuticals|Novartis June 2013 Phase 1
NCT01685060 Completed Drug: LDK378 Non-Small Cell Lung Cancer Novartis Pharmaceuticals|Novartis November 26 2012 Phase 2
NCT01634763 Completed Drug: LDK378 Tumors Characterized by Genetic Alterations in Anaplastic Lymphoma Kinase (ALK) Novartis Pharmaceuticals|Novartis June 2012 Phase 1

技术支持

在订购、运输、储存和使用我们的产品的任何阶段,您遇到的任何问题,均可以通过拨打我们的热线电话400-668-6834,或者技术支持邮箱tech@selleck.cn,直接联系到我们。我们会在24小时内尽快联系您。

操作手册

如果有其他问题,请给我们留言。

  • * 必填项

常见问题及建议解决方法

  • 问题 1:

    how to reconstitute the inhibitor for oral administration to mice?

  • 回答:

    You can resuspend LDK378 in 30% PEG400/0.5% Tween 80/5% propylene glycol and use the suspension for oral gavage feeding.

ALK Signaling Pathway Map

ALK Inhibitors with Unique Features

相关ALK产品

Tags: 购买Ceritinib (LDK378) | Ceritinib (LDK378)供应商 | 采购Ceritinib (LDK378) | Ceritinib (LDK378)价格 | Ceritinib (LDK378)生产 | 订购Ceritinib (LDK378) | Ceritinib (LDK378)代理商
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID