Shipping services continue despite COVID-19 outbreak ! Click here to view COVID-19 related products

Ceritinib (LDK378)

For research use only.

Catalog No.S7083

64 publications

Ceritinib (LDK378) Chemical Structure

CAS No. 1032900-25-6

Ceritinib (LDK378) is potent inhibitor against ALK with IC50 of 0.2 nM in cell-free assays. Ceritinib (LDK378) also inhibits IGF-1R, InsR, STK22D and FLT3 with IC50 of 8 nM, 7 nM, 23 nM and 60 nM, respectively. Phase 3.

Size Price Stock Quantity  
USD 147 In stock
USD 470 In stock
USD 1309 In stock
Bulk Discount

Free Overnight Delivery on orders over $ 500
Next day delivery by 10:00 a.m. Order now.

Selleck's Ceritinib (LDK378) has been cited by 64 publications

Purity & Quality Control

Choose Selective ALK Inhibitors

Biological Activity

Description Ceritinib (LDK378) is potent inhibitor against ALK with IC50 of 0.2 nM in cell-free assays. Ceritinib (LDK378) also inhibits IGF-1R, InsR, STK22D and FLT3 with IC50 of 8 nM, 7 nM, 23 nM and 60 nM, respectively. Phase 3.
Features Does not cross react with c-Met, and has an improved in vivo glucose homeostasis profile relative to TAE684. May be active in Crizotinib-relapsed tumors.
Targets
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
In vitro

LDK378 shows great anti-proliferative activity in Ba/F3-NPM-ALK and Karpas290 cells with IC50 of 26.0 nM and 22.8 nM, compared with IC50 of 319.5 nM and 2477 nM in Ba/F3-Tel-InsR and Ba/F3-WT cells. [1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Parental(+IL3) NWThT41ST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3rn[VczKGh? MUDEUXNQ NHO2S4pKSzVyPUG1PFYhyrFiMUezJI5O MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd2OUCzOEc,OjV5NEmwN|Q9N2F-
WT 70 NFXrXFhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1\tPVczKGh? NUPvdIpyTE2VTx?= MlHBTWM2OD1{MTFCtUA5KG6P MnLvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5NEmwN|QoRjJ3N{S5NFM1RC:jPh?=
G1128S 1022 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEntWWw4OiCq NYDWd3BWTE2VTx?= MWnJR|UxRTFyMjFCtUA{QCCwTR?= NYjqcopKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3OFkxOzRpPkK1O|Q6ODN2PD;hQi=>
C1156F 1293 NYnQdlRGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWG3NkBp NX\GW|NvTE2VTx?= NEmzXW1KSzVyPUKxO{DDuSBzMUWgcm0> MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd2OUCzOEc,OjV5NEmwN|Q9N2F-
I1171N 519 NHjBPYNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYP6[5VkPzJiaB?= MkTqSG1UVw>? MVrJR|UxRTF6NzFCtUA5PyCwTR?= NH;PWXM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe0PVA{PCd-MkW3OFkxOzR:L3G+
I1171T 445 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlrSO|IhcA>? NH6xVnlFVVOR Ml6zTWM2OD16MjFCtUAyOiCwTR?= M2Xz[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{S5NFM1Lz5{NUe0PVA{PDxxYU6=
F1174I 184 NXLC[Ik5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1\jOFczKGh? Mk\uSG1UVw>? MYfJR|UxRTF|INMxJFAvOSCwTR?= MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd2OUCzOEc,OjV5NEmwN|Q9N2F-
N1178H 169 MmDIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2G3TFczKGh? NI\TXndFVVOR NHTDcXlKSzVyPUSyJOKyKDZibl2= NXLjOJpQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3OFkxOzRpPkK1O|Q6ODN2PD;hQi=>
E1210K 748 NIDJWYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoLnO|IhcA>? NHHMS5pFVVOR NH7lW3BKSzVyPUG4O{DDuSB6NDDuUS=> M1rBN|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{S5NFM1Lz5{NUe0PVA{PDxxYU6=
C1156F/D1203N 2809 MmPjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1XWflczKGh? NIPEO|dFVVOR M{XyNGlEPTB;MkW0JOKyKDl7IH7N MmrvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5NEmwN|QoRjJ3N{S5NFM1RC:jPh?=
Ba/F3 NA WT M1\ONGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVS3NkBp M3LkOWlEPTB;MD6wNlAh|ryP NYXhRpRqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3Nlc1ODBpPkK1O|I4PDByPD;hQi=>
Ba/F3 NA C1156Y NU\yeYwzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXy3NkBp MoTHTWM2OD1yLkC3NUDPxE1? NFnSe2I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyO|QxOCd-MkW3Nlc1ODB:L3G+
Ba/F3 NA L1196M NXS0SGc2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGXB[5Q4OiCq M2fGOWlEPTB;MD6wOFIh|ryP NU\KVWdHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3Nlc1ODBpPkK1O|I4PDByPD;hQi=>
Ba/F3 NA L1152R Mn\lS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXPBO5ZmPzJiaB?= NUezPVB4UUN3ME2wMlI5QCEQvF2= MofVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5Mke0NFAoRjJ3N{K3OFAxRC:jPh?=
Ba/F3 NA G1202R MljhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHzHRWg4OiCq NWXTdHpZUUN3ME2wMlI4PyEQvF2= NH\XPVY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyO|QxOCd-MkW3Nlc1ODB:L3G+
Ba/F3 NA G1269A MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmrkO|IhcA>? NV;GV2pLUUN3ME2wMlAyQSEQvF2= NEjobGc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyO|QxOCd-MkW3Nlc1ODB:L3G+
Ba/F3 NA S1206Y NUHXcW5ZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXi3NkBp MlzrTWM2OD1yLkCzO{DPxE1? Mo[zQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5Mke0NFAoRjJ3N{K3OFAxRC:jPh?=
Ba/F3 EA WT MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3LjVlczKGh? NV7nSpl5UUN3ME2wMlAzOSEQvF2= NEnlc4s9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyO|QxOCd-MkW3Nlc1ODB:L3G+
Ba/F3 EA C1156Y NIfqeFBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NG\ScYs4OiCq NFnVUGZKSzVyPUCuNFI3KM7:TR?= M2XOXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{K3OFAxLz5{NUeyO|QxODxxYU6=
Ba/F3 EA L1196M NW\FO3dDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3XrdlczKGh? NUPGXpp3UUN3ME2wMlAyQSEQvF2= MnnaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5Mke0NFAoRjJ3N{K3OFAxRC:jPh?=
Ba/F3 EA L1152R MlHBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mnv2O|IhcA>? M{fXO2lEPTB;MD6wPVkh|ryP MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd{N{SwNEc,OjV5Mke0NFA9N2F-
Ba/F3 EA G1202R MoPZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEjlRpg4OiCq Mo\rTWM2OD1yLkS2O{DPxE1? Mk\OQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5Mke0NFAoRjJ3N{K3OFAxRC:jPh?=
Ba/F3 EA G1269A M1LYXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1XNdFczKGh? NWjjUFRFUUN3ME2wMlA{OyEQvF2= M{XkN|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{K3OFAxLz5{NUeyO|QxODxxYU6=
Ba/F3 EA S1206Y MlXCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWTXPWFtPzJiaB?= MV7JR|UxRTBwMEO4JO69VQ>? MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd{N{SwNEc,OjV5Mke0NFA9N2F-
BAF3 Ml7nRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? M{fLblczKGi{cx?= MnH1RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDtc5V{\SCEQV[zJINmdGy|IHjhdoJwemmwZzDFUWw1NUGOSzDh[pRmeiB5MjDodpMh[nliU2LCJI9zKEOFS{igZZN{[XluIFnDOVAhRSByLkCxNFch|ryPLh?= NIC3NIY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUK4PFk1OCd-MkmyPFg6PDB:L3G+
NCI-H3122 NIXt[lNCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MXe3NkBpenN? M3K2WGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTlPJMWg{OTJ{IHPlcIx{KGGodHXyJFczKGi{czDifUBE\WyuVHn0[ZIuT2yxIFz1cYlv\XOlZX70JGNmdGxiVnnhZoltcXS7IFHzd4F6NCCHQ{WwJF0hOC5yMUWg{txONg>? NUjmVFlxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1OlgzQDlpPkK2OVY5Ojh7PD;hQi=>
NCI-H2228 MXXHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NWjZS3QzOyCmYYnz MluxS5Jwf3SqIHnubIljcXSrb36gc4YhcHWvYX6gUmNKNUh{MkK4JINmdGy|IHHmeIVzKDNiZHH5d{BjgSCudX3pcoV{[2WwY3WtZoF{\WRiQ3XscHRqfGW{LVfsc{Bie3OjeTygTWM2OCB;IECuNFE2KM7:TT6= M{f0T|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NkK3O|I2Lz5{OU[yO|czPTxxYU6=
SU-DHL1 MmnDS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NUS1TmRTOyCmYYnz MYHHdo94fGhiaX7obYJqfGmxbjDv[kBpfW2jbjDTWU1FUExzIHPlcIx{KGGodHXyJFMh\GG7czDifUBtfW2rbnXzZ4Vv[2VvYnHz[YQhS2WubGTpeIVzNUeubzDhd5NigSxiSVO1NEA:KDBwMEG1JO69VS5? M2PnWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NkK3O|I2Lz5{OU[yO|czPTxxYU6=
DFCI114 M1TVVWFvfGmycn;sbYZmemG2aY\lJIF{e2G7 Mki5O|IhcHK| NXXHc3k2SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDESmNKOTF2IHPlcIx{KGW6cILld5NqdmdiRV3MOE1CVEtiR{GyOllCKG23dHHueEBi\nSncjC3NkBpenNiYomgR4VtdFSrdHXyMWdtdyCOdX3pcoV{[2WwdDDD[YxtKF[rYXLpcIl1gSCDc4PhfUwhTUN3MDC9JFAvODF6IN88UU4> MnHGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3NkiyPFkoRjJ4NU[4Nlg6RC:jPh?=
HCC78 Mn7yR5l1d3SxeHnjbZR6KGG|c3H5 M2PGRVczKGi{cx?= MkWxR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gTGNEPzhiY3XscJMhcGG{Yn;ybY5oKFOOQ{O0RVIuWk:VMTDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5iY3XscEBxem:uaX\ldoF1cW:wIHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVAhRSByLkCxPEDPxE1w NGHOZpA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{S3OFkzPSd-Mke0O|Q6OjV:L3G+
KARPAS299 MWrDfZRwfG:6aXPpeJkh[XO|YYm= MmTTNkB1dyB|IHThfZM> MonuR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gT2FTWEGVMkm5JINmdGy|IHHmeIVzKDJidH:gN{Bl[Xm|IHL5JIx2[2moZYLhd4UhemWyb4L0[ZIh\2WwZTDhd5NigSxiSVO1NEA:KDBwMEKyPEDPxE1w M1r2NlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|N{SyNlUzLz5{M{e0NlI2OjxxYU6=
KARPAS299 NGjUO|dEgXSxdH;4bYNqfHliYYPzZZk> NXXJ[2pUS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hU0GUUFHTNlk6KGOnbHzzJIV5eHKnc4PpcochVlCPLVHMT{BnfXOrb36g[4Vv\SCjc4Pld5Nm\CCjczDndo94fGhiaX7obYJqfGmxbjygTWM2OCB;IECuNFIzQCEQvF2u NWnlWoV1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO4N|c4QTdpPkKzPFM4Pzl5PD;hQi=>
NCI-H3122 MXzGeY5kfGmxbjDhd5NigQ>? NIjRZpg4OiCqcoO= NIHYb3FKdmirYnn0bY9vKG:oIFXNUFQh\nW|ZXSgRWxMKGmwIHj1cYFvKE6FST3IN|EzOiClZXzsd{Bie3Onc4Pl[EBieyClZXzsJIdzd3e2aDDpcohq[mm2aX;uJI1m[XO3cnXkJIFnfGW{IEeyJIhzeyCkeTDTVmIh[XO|YYmsJGNEPTBiPTCwMlAzPSEQvF2u NFfLR4w9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{mxOVE3QSd-Mke5NVUyPjl:L3G+
BAF3 MkfkSpVv[3Srb36gZZN{[Xl? NGnCUVczKHSxIEOg[IF6ew>? MXPJcohq[mm2aX;uJI9nKE6STT3meZNm\CCDTFugLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO|ZXSgbY4hdW:3c3WgRmFHOyClZXzsd{Bi\nSncjCyJJRwKDNiZHH5d{BjgSCudXPp[oVz[XOnIILldI9zfGW{IHflcoUh[XO|YYmsJGlEPTBiPTCwMlAzPiEQvF2u NHja[2o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e0NlI2Oid-MkO3OFIzPTJ:L3G+
BA/F3 NFW2UoZEgXSxdH;4bYNqfHliYYPzZZk> NVXQT28yS3m2b4TvfIlkcXS7IHHnZYlve3RibX;1d4UhSkFxRkOgZ4VtdHNiZYjwdoV{e2mwZzDOVG0uSUyNIH\1d4lwdiCpZX7lJIF{e2W|c3XkJIF{KGe{b4f0bEBqdmirYnn0bY9vNCCLQ{WwJF0hOC5yMk[g{txONg>? M1PuZ|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|OEO3O|k4Lz5{M{izO|c6PzxxYU6=
KARPAS299 MkjTRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? MnvmO|IhcHK| NFHsfWFCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFvBVnBCWzJ7OTDj[YxteyCqYYLic5JqdmdiTmDNMWFNUyCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwJF0hOC5yMk[g{txONg>? NFLvSnI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUG3OFgxQSd-MkmxO|Q5ODl:L3G+
NCI-H2228 M1;pRWFvfGmycn;sbYZmemG2aY\lJIF{e2G7 NV24b3FXPzJiaILz NXjFTJBpSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDOR2kuUDJ{MkigZ4VtdHNiaHHyZo9zcW6pIFXNUFQuSUyNIHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVAhRSByLkCyOkDPxE1w NX3IfGliRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CyNlMyOjBpPkOwNlI{OTJyPD;hQi=>
KARPAS299 MVrDfZRwfG:6aXPpeJkh[XO|YYm= NHL4Oo44OiCqcoO= M3f5SmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGtCWlCDU{K5PUBk\WyuczDoZZJjd3KrbnegUnBONUGOSzDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5iY3XscEBxem:uaX\ldoF1cW:wIHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVAhRSByLkCyO{DPxE1w MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzR5NEmyOUc,Ojd2N{S5NlU9N2F-
Ba/F3 NY\Qd2lCTnWwY4Tpc44h[XO|YYm= Mkf4O|IhcHK| Mo\oTY5pcWKrdHnvckBw\iCHTVy0MWFNUyCVMUKwOnkhdXW2YX70JEh2dmuwb4fuJI9zcWerbjmg[ZhxemW|c3XkJIlvKG2xdYPlJGJiN0Z|IHPlcIx{KGG|c3Xzd4VlKGG|IHPlcIwhfmmjYnnsbZR6KGGodHXyJFczKGi{czDifUBOXFNiYYPzZZktKEmFNUCgQUAxNjB|MzFOwG0v NYfMNmdkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1OlgzQDlpPkK2OVY5Ojh7PD;hQi=>
NCI-H3122 M4fNfmFvfGmycn;sbYZmemG2aY\lJIF{e2G7 NYnUcVRDSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEB4cWymIIT5dIUhcHWvYX6gUmNKNUh|MUKyJINmdGy|LDDDR|UxKD1iMD6wN|gh|ryPLh?= NFvsPGw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkKzOVk1PSd-Mk[yN|U6PDV:L3G+
NCI-H3122 M3WxOGZ2dmO2aX;uJIF{e2G7 NH:wRVc4OiCqcoO= M3u1ZWlvcGmkaYTpc44hd2ZiRV3MOE1CVEtiaX6gbJVu[W5iTlPJMWg{OTJ{IHPlcIx{KGG|c3Xzd4VlKGG|IHnubIljcXSrb36gc4Yh[2WubDDwdo9tcW[ncnH0bY9vKGGodHXyJFczKGi{czDifUBUWkJiYYPzZZktKEOFNUCgQUAxNjB|ODFOwG0v M32xT|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4OUKzOlk2Lz5{NkmyN|Y6PTxxYU6=
NCI-H3122 NYG5S2pYTnWwY4Tpc44h[XO|YYm= NX3IOY1uPzJiaILz NX\L[ldRUW6qaXLpeIlwdiCxZjDFUWw1NUGOSzDpckBpfW2jbjDOR2kuUDNzMkKgZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iClZXzsJJBzd2yrZnXyZZRqd25iYX\0[ZIhPzJiaILzJIJ6KFOUQjDhd5NigSxiQ1O1NEA:KDBwMEO4JO69VS5? MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjl{M{[5OUc,OjZ7MkO2PVU9N2F-
NCI-H3122 M{iwO2Z2dmO2aX;uJIF{e2G7 NHT0PZM4OiCqcoO= NYDm[JZ5UW6qaXLpeIlwdiCxZjDFUWw1KG[3c3XkJGFNUyCrbjDoeY1idiCQQ1mtTFMyOjJiY3XscJMh[XO|ZYPz[YQh[XNiY3XscEBoem:5dHigbY5pcWKrdHnvckBi\nSncjC3NkBpenNiYomgV3JDKGG|c3H5MEBESzVyIE2gNE4xOzhizszNMi=> NELWVWc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEO4OVUxPSd-MkizPFU2ODV:L3G+
BA/F3 NITYRlhHfW6ldHnvckBie3OjeR?= Ml;2TY5pcWKrdHnvckBw\iCDTFugLJVvc26xd36gc5Jq\2mwKTD0doFve2[nY4Tl[EBqdiCvb4Xz[UBDSS:IMzDj[YxteyxiSVO1NEA:KDBwMESwO{DPxE1w NGLEUpg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{izO|c6Pyd-MkO4N|c4QTd:L3G+
Ba/F3 MYDGeY5kfGmxbjDhd5NigQ>? NFHLXXk4OiCqcoO= NIP2S|dKdmirYnn0bY9vKG:oIIfpcIQhfHmyZTDFUWw1NUGOSzCoeY5sdm:5bjDvdolocW5rIHX4dJJme3OnZDDpckBud3W|ZTDCZU9HOyClZXzsd{Bie3Onc4Pl[EBieyClZXzsJJZq[WKrbHn0fUBi\nSncjC3NkBpenNiYomgUXRUKGG|c3H5MEBKSzVyIE2gNE4xPDFizszNMi=> MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjV4OEK4PUc,OjZ3NkiyPFk9N2F-
Ba/F3 MnfNSpVv[3Srb36gZZN{[Xl? MorpO|IhcHK| MWXJcohq[mm2aX;uJI9nKHerbHSgeJlx\SCHTVy0MWFNUyBqdX7rco94diCxcnnnbY4qKGW6cILld5Nm\CCrbjDtc5V{\SCEYT;GN{Bk\WyuczDhd5Nme3OnZDDhd{Bk\WyuII\pZYJqdGm2eTDh[pRmeiB5MjDodpMh[nliTWTTJIF{e2G7LDDJR|UxKD1iMD6wOFEh|ryPLh?= M1rXW|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NU[4Nlg6Lz5{NkW2PFI5QTxxYU6=
KARPAS299 NU\qUpg5SW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= MV[3NkBpenN? MlX3RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCNQWLQRXMzQTliY3XscJMhcGG{Yn;ybY5oKE6STT3BUGsh[W[2ZYKgO|IhcHK|IHL5JG1VXCCjc4PhfUwhUUN3MDC9JFAvODRzIN88UU4> NFj4UpE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MEKyN|EzOCd-M{CyNlMyOjB:L3G+
BAF3 MYTBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? MXu3NkBpenN? MkK5RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDtc5V{\SCEQV[zJINmdGy|IHjhdoJwemmwZzDFUWw1NUGOSzDMNVE6Pk1ibYX0ZY51KGGodHXyJFczKGi{czDifUBUWkJib4KgR2NMQCCjc4PhfUwhUUN3MDC9JFAvODV2OTFOwG0v NGnaU|E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUK4PFk1OCd-MkmyPFg6PDB:L3G+
Ba/F3 MWDGeY5kfGmxbjDhd5NigQ>? NUTDNXZ6PzJiaILz NXLJflc3UW6qaXLpeIlwdiCxZjDFUWw1NUGOSzDHNVI3QUFibYX0ZY51KCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIH3veZNmKEKjL1[zJINmdGy|IHHzd4V{e2WmIHHzJINmdGxidnnhZoltcXS7IHHmeIVzKDd{IHjyd{BjgSCPVGOgZZN{[XluIFnDOVAhRSByLkC1O{DPxE1w MofFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3NkiyPFkoRjJ4NU[4Nlg6RC:jPh?=
HCC78 NW\ZR2g5SW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NHrwbow4OiCqcoO= NX\vNZNqSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDIR2M4QCClZXzsd{Bp[XKkb4LpcochW0yFM{TBNk1TV1NzIHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVAhRSByLkC1PEDPxE1w MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTF5NEiwPUc,OjlzN{S4NFk9N2F-
HCC78 M{Xn[WFvfGmycn;sbYZmemG2aY\lJIF{e2G7 MYK3NkBpenN? MXfBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEiFQ{e4JINmdGy|IHjhdoJwemmwZzDTUGM{PEF{LWLPV|Eh[W[2ZYKgO|IhcHK|IHL5JG1VXCCjc4PhfUwhUUN3MDC9JFAvODV6IN88UU4> MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODJ{M{GyNEc,OzB{MkOxNlA9N2F-
Ba/F3 MWLGeY5kfGmxbjDhd5NigQ>? MYe3NkBpenN? NVu1ZWhXUW6qaXLpeIlwdiCxZjDFUWw1NUGOSzDMNVE6Pk1ibYX0ZY51KCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIH3veZNmKEKjL1[zJINmdGy|IHHzd4V{e2WmIHHzJINmdGxidnnhZoltcXS7IHHmeIVzKDd{IHjyd{BjgSCPVGOgZZN{[XluIFnDOVAhRSByLkC2OEDPxE1w MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjV4OEK4PUc,OjZ3NkiyPFk9N2F-
DFCI76 MVHBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? MlHhO|IhcHK| NUTKUoh[SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDESmNKPzZiY3XscJMh\XiycnXzd4lv\yCHTVy0MWFNUyCOMUG1NnIhdXW2YX70JIFnfGW{IEeyJIhzeyCkeTDD[YxtXGm2ZYKtS4xwKEy3bXnu[ZNk\W62IFPlcIwhXmmjYnnsbZR6KEG|c3H5MEBGSzVyIE2gNE4xPzJizszNMi=> NVm2WFA4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1OlgzQDlpPkK2OVY5Ojh7PD;hQi=>
BAF3 MkTFRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? NVXvS4wySW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBud3W|ZTDCRWY{KGOnbHzzJIV5eHKnc4PpcochSUyNIFyxNVk3VSCvdYThcpQtKEOFNUCgQUAxNjB5NTFOwG0v NX7tN29bRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[yN|U6PDVpPkK2NlM2QTR3PD;hQi=>
BA/F3 NHfZRYdHfW6ldHnvckBie3OjeR?= MXS3NkBpenN? M1q5UGlvcGmkaYTpc44hd2ZiQVzLJGwyOTl4TTDteZRidnRiaX6gcY92e2ViQlGvSlMh[2WubIOgZZN{\XO|ZXSgZZMhcW6qaXLpeIlwdiCxZjDj[YxtKHC{b3zp[oVz[XSrb36gZYZ1\XJiN{KgbJJ{KGK7IGfTWFEh[XO|YYmsJGNEPTBiPTCwMlA4PSEQvF2u NVTtWFV3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[5NlM3QTVpPkK2PVI{Pjl3PD;hQi=>
BA/F3 NGTke5lHfW6ldHnvckBie3OjeR?= NEmzeXg4OiCqcoO= NEDtSmNKdmirYnn0bY9vKG:oIFXNUFQh\nW|ZXSgRWxMKExzMUm2UUBufXSjboSgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO|ZXSgbY4hdW:3c3WgRmEwTjNiY3XscJMh[XO|ZYPz[YQh[XNiY3XscEBoem:5dHigbY5pcWKrdHnvckBu\WG|dYLl[EBi\nSncjC3NkBpenNiYomgV3JDKGG|c3H5MEBESzVyIE2gNE4xPzVizszNMi=> MmHwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd7MUWxOlkoRjJ5OUG1NVY6RC:jPh?=
BA/F3 M{DON2Z2dmO2aX;uJIF{e2G7 MkHrO|IhcHK| M1HXemlvcGmkaYTpc44hd2ZiRV3MOEBnfXOnZDDBUGshMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5ibX;1d4UhSkFxRkOgZ4VtdHNiYYPz[ZN{\WRiYYOgZ4VtdCCpcn;3eIghcW6qaXLpeIlwdiCvZXHzeZJm\CCjZoTldkA4OiCqcoOgZpkhW1KEIHHzd4F6NCCFQ{WwJF0hOC5yN{Wg{txONg>? MmfPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd7MUWxOlkoRjJ5OUG1NVY6RC:jPh?=
BAF3 M2PR[mZ2dmO2aX;uJIF{e2G7 MYS3NkBpenN? NGjDUnFKdmirYnn0bY9vKG:oIFHMT{BNOTF7Nl2gcZV1[W62IDj1cotvd3ewIH;ybYdqdiliZYjwdoV{e2WmIHnuJI1wfXOnIFLBSlMh[2WubIOgZZN{\XO|ZXSgZZMh[2WubDDndo94fGhiaX7obYJqfGmxbjDh[pRmeiB5MjDodpMh[nliV2PUMVEh[XO|YYmsJGNEPTBiPTCwMlA4PSEQvF2u MnT5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjh|OEW1NFUoRjJ6M{i1OVA2RC:jPh?=
KARPAS299 MlriRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? MXy3NkBpenN? Ml7VRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCNQWLQRXMzQTliY3XscJMhcGG{Yn;ybY5oKE6STT3BUGsh[W[2ZYKgO|IhcHK|IHL5JHNTSiCxcjDDR2s5KGG|c3H5MEBKSzVyIE2gNE4xQDRizszNMi=> NVT5dnQ6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmyPFg6PDBpPkK5Nlg5QTRyPD;hQi=>
SMS-KCNR M1ruRWFvfGmycn;sbYZmemG2aY\lJIF{e2G7 M1zDbVczKGi{cx?= NXz0d2N{SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDTUXMuU0OQUjDj[YxteyCneIDy[ZN{cW6pIFXNUFQuSUyNIGKxNlc2WSCvdYThcpQh[W[2ZYKgO|IhcHK|IHL5JGNmdGyWaYTldk1IdG9iTIXtbY5me2OnboSgR4VtdCCYaXHibYxqfHliQYPzZZktKEWFNUCgQUAxNjB7MjFOwG0v MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjV4OEK4PUc,OjZ3NkiyPFk9N2F-
NCI-H3122 MYnBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? NHvSSpk4OiCqcoO= MkfLRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCQQ1mtTFMyOjJiY3XscJMh[W[2ZYKgO|IhcHK|IHL5JHNTSiCxcjDDR2s5KGG|c3H5MEBKSzVyIE2gNE4xQTZizszNMi=> NVPHXHZ5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmyPFg6PDBpPkK5Nlg5QTRyPD;hQi=>
NCI-H2228 MWXBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? MY[3NkBpenN? M17LZWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTlPJMWgzOjJ6IHPlcIx{KGijcnLvdolv\yCHTVy0MWFNUyCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwJF0hOC5yOUmg{txONg>? MkjUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjlzN{S4NFkoRjJ7MUe0PFA6RC:jPh?=
Ba/F3 M2\FOmZ2dmO2aX;uJIF{e2G7 NInsNIg4OiCqcoO= Mnz2TY5pcWKrdHnvckBw\iCHTVy0MWFNUyCIMUG3OGwhdXW2YX70JEh2dmuwb4fuJI9zcWerbjmg[ZhxemW|c3XkJIlvKG2xdYPlJGJiN0Z|IHPlcIx{KGG|c3Xzd4VlKGG|IHPlcIwhfmmjYnnsbZR6KGGodHXyJFczKGi{czDifUBOXFNiYYPzZZktKEmFNUCgQUAxNjFyMTFOwG0v NVHUTJAyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1OlgzQDlpPkK2OVY5Ojh7PD;hQi=>
NCI-H2228 MV;DfZRwfG:6aXPpeJkh[XO|YYm= NYHDZXlkPzJiaILz M4fLVmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJG5EUS2KMkKyPEBk\WyuczDhd5Nme3OnZDDhd{Bk\WyuII\pZYJqdGm2eTDh[pRmeiB5MjDodpMh[nliTWTTJIF{e2G7LDDJR|UxKD1iMD6xNFI3KM7:TT6= Moi4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV4NES2O|EoRjJ3NkS0OlcyRC:jPh?=
LAN5 M4XafGFvfGmycn;sbYZmemG2aY\lJIF{e2G7 MVi3NkBpenN? MlrtRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCOQV61JINmdGy|IHX4dJJme3OrbnegSW1NPC2DTFugVlEzPzWTIH31eIFvfCCjZoTldkA4OiCqcoOgZpkhS2WubGTpeIVzNUeubzDMeY1qdmW|Y3XueEBE\WyuIG\pZYJqdGm2eTDBd5NigSxiRVO1NEA:KDBwMUKyJO69VS5? NGfNeJk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkW2PFI5QSd-Mk[1OlgzQDl:L3G+
SU-DHL1 NGO5cGJCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= M4W0dlczKGi{cx?= MnjSRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCVVT3ETGwyKGOnbHzzJIhiemKxcnnu[{BPWE1vQVzLJIFnfGW{IEeyJIhzeyCkeTDTVmIhd3JiQ1PLPEBie3OjeTygTWM2OCB;IECuNVIzKM7:TT6= NETZe5o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUK4PFk1OCd-MkmyPFg6PDB:L3G+
Kelly NGLU[m9CdnSrcILvcIln\XKjdHn2[UBie3OjeR?= M1ezclczKGi{cx?= NHPldHRCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFvlcIx6KGOnbHzzJIV5eHKnc4PpcochTU2OND3BUGshTjFzN{TMJI12fGGwdDDh[pRmeiB5MjDodpMh[nliQ3XscHRqfGW{LVfsc{BNfW2rbnXzZ4VvfCCFZXzsJHZq[WKrbHn0fUBCe3OjeTygSWM2OCB;IECuNVQzKM7:TT6= MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjV4OEK4PUc,OjZ3NkiyPFk9N2F-
Ba/F3 NX:wVJlbTnWwY4Tpc44h[XO|YYm= M2fleFczKGi{cx?= M17ObmlvcGmkaYTpc44hd2ZiRV3MOE1CVEtiQ{GxOVZ[KG23dHHueEApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCvb4Xz[UBD[S:IMzDj[YxteyCjc4Pld5Nm\CCjczDj[YxtKH[rYXLpcIl1gSCjZoTldkA4OiCqcoOgZpkhVVSVIHHzd4F6NCCLQ{WwJF0hOC5zNkSg{txONg>? M3LQfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NU[4Nlg6Lz5{NkW2PFI5QTxxYU6=
SH-SY5Y M1Hwd2FvfGmycn;sbYZmemG2aY\lJIF{e2G7 MmK2O|IhcHK| NYPyeGVRSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDTTE1UYTW\IHPlcIx{KGW6cILld5NqdmdiRV3MOE1CVEtiRkGxO|RNKG23dHHueEBi\nSncjC3NkBpenNiYomgR4VtdFSrdHXyMWdtdyCOdX3pcoV{[2WwdDDD[YxtKF[rYXLpcIl1gSCDc4PhfUwhTUN3MDC9JFAvOTh4IN88UU4> NFTaenU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkW2PFI5QSd-Mk[1OlgzQDl:L3G+
BAF3 NHq3endCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= Mn3IO|IhcHK| MX\BcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IH3veZNmKEKDRkOgZ4VtdHNiaHHyZo9zcW6pIFPEO|QuWk:VMTDh[pRmeiB5MjDodpMh[nliU2LCJI9zKEOFS{igZZN{[XluIFnDOVAhRSByLkKzOEDPxE1w M4DPRVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7Mki4PVQxLz5{OUK4PFk1ODxxYU6=
SK-N-SH NH;pclVCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MX:3NkBpenN? M3T5cGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iU1utUk1UUCClZXzsd{BmgHC{ZYPzbY5oKEWPTEStRWxMKEZzMUe0UEBufXSjboSgZYZ1\XJiN{KgbJJ{KGK7IFPlcIxVcXSncj3HcI8hVHWvaX7ld4NmdnRiQ3XscEBXcWGkaXzpeJkhSXO|YYmsJGVEPTBiPTCwMlMxOyEQvF2u MlztQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3NkiyPFkoRjJ4NU[4Nlg6RC:jPh?=
BAF3 MlPQSpVv[3Srb36gZZN{[Xl? M3vLVVIhfG9iMzDkZZl{ MUDJcohq[mm2aX;uJI9nKFSHTD3meZNm\CCrboP1cIlvKHKnY3XweI9zKCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIH3veZNmKEKDRkOgZ4VtdHNiYX\0[ZIhOiC2bzCzJIRigXNiYomgcJVkcW[ncnHz[UBz\XCxcoTldkBo\W6nIHHzd4F6NCCLQ{WwJF0hOC5|MUm1JO69VS5? MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd2MkK1Nkc,OjN5NEKyOVI9N2F-
BA/F3 M{DabWN6fG:2b4jpZ4l1gSCjc4PhfS=> MoDjR5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmEwTjNiY3XscJMhfHKjboPm[YN1\WRid3n0bEBV\WxvSX7zVkBo\W6nIHHzd4V{e2WmIHHzJIdzd3e2aDDpcohq[mm2aX;uMEBKSzVyIE2gNE4{OiEQvF2u NFjqVIY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{izO|c6Pyd-MkO4N|c4QTd:L3G+
SK-N-FI MYLBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? MWq3NkBpenN? NI\2d4pCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGPLMW4uTkliY3XscJMh\XiycnXzd4lv\yC5aXzkJJR6eGViRV3MOE1CVEtiYX\0[ZIhPzJiaILzJIJ6KEOnbHzUbZRmei2JbH:gUJVucW6nc3PlcpQhS2WubDDWbYFjcWyrdImgRZN{[XluIFXDOVAhRSByLkO0PUDPxE1w MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjV4OEK4PUc,OjZ3NkiyPFk9N2F-
CHLA20 MnzZRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? Mm\6O|IhcHK| M13rNWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iQ1jMRVIxKGOnbHzzJIV5eHKnc4PpcochTU2OND3BUGshWjF{N{XRJI12fGGwdDDh[pRmeiB5MjDodpMh[nliQ3XscHRqfGW{LVfsc{BNfW2rbnXzZ4VvfCCFZXzsJHZq[WKrbHn0fUBCe3OjeTygSWM2OCB;IECuN|Y{KM7:TT6= MmC1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3NkiyPFkoRjJ4NU[4Nlg6RC:jPh?=
Ba/F3 MV\GeY5kfGmxbjDhd5NigQ>? MWq3NkBpenN? NEG2UlRKdmirYnn0bY9vKG:oIFXNUFQuSUyNIFexNlAzWiCvdYThcpQhMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5ibX;1d4UhSmFxRkOgZ4VtdHNiYYPz[ZN{\WRiYYOgZ4VtdCC4aXHibYxqfHliYX\0[ZIhPzJiaILzJIJ6KE2WUzDhd5NigSxiSVO1NEA:KDBwNES0JO69VS5? NUTJT2xbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1OlgzQDlpPkK2OVY5Ojh7PD;hQi=>
LAN1 Mmi5RY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? NIiwT4s4OiCqcoO= NHrmbFZCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFzBUlEh[2WubIOg[ZhxemW|c3nu[{BGVUx2LVHMT{BHOTF5NFygcZV1[W62IHHmeIVzKDd{IHjyd{BjgSCFZXzsWIl1\XJvR3zvJGx2dWmwZYPj[Y51KEOnbHygWoli[mmuaYT5JGF{e2G7LDDFR|UxKD1iMD61OFkh|ryPLh?= NUTK[nlNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1OlgzQDlpPkK2OVY5Ojh7PD;hQi=>
SK-N-BE(2) NGnNV4hCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= M3fFb|czKGi{cx?= NFTOeYxCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGPLMW4uSkVqMjmgZ4VtdHNiZYjwdoV{e2mwZzD3bYxlKHS7cHWgSW1NPC2DTFugZYZ1\XJiN{KgbJJ{KGK7IFPlcIxVcXSncj3HcI8hVHWvaX7ld4NmdnRiQ3XscEBXcWGkaXzpeJkhSXO|YYmsJGVEPTBiPTCwMlU6OyEQvF2u MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjV4OEK4PUc,OjZ3NkiyPFk9N2F-
Ba/F3 MVfGeY5kfGmxbjDhd5NigQ>? NYTHUWR6PzJiaILz NXToVZJVUW6qaXLpeIlwdiCxZjDFUWw1NUGOSzCxNVUyXGmwczDteZRidnRiKIXub45wf25ib4Lp[4lvMSCneIDy[ZN{\WRiaX6gcY92e2ViQnGvSlMh[2WubIOgZZN{\XO|ZXSgZZMh[2WubDD2bYFjcWyrdImgZYZ1\XJiN{KgbJJ{KGK7IF3UV{Bie3OjeTygTWM2OCB;IECuOlY5KM7:TT6= NWO3eVdYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1OlgzQDlpPkK2OVY5Ojh7PD;hQi=>
BAF3 MVHBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? Mmq4O|IhcHK| MX7BcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IH3veZNmKEKDRkOgZ4VtdHNiaHHyZo9zcW6pIFXNUFQuSUyNIFexNlAzWiCvdYThcpQh[W[2ZYKgO|IhcHK|IHL5JHNTSiCxcjDDR2s5KGG|c3H5MEBKSzVyIE2gNE44OjZizszNMi=> MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTJ6OEm0NEc,Ojl{OEi5OFA9N2F-
Ba/F3 Mn7GSpVv[3Srb36gZZN{[Xl? MVe3NkBpenN? Mmr4TY5pcWKrdHnvckBw\iCqdX3hckBGT0[UIHTlcFE6N1R5OUDNM2M4QTeVIH31eIFvfCCneIDy[ZN{\WRiaX6gcY92e2ViQnGvSlMh[2WubIOgZZN{\XO|ZXSgZZMh[2WubDDndo94fGhiaX7obYJqfGmxbjDh[pRmeiB5MjDodpMh[nliQ3XscHRqfGW{LVfsc{Bie3OjeTygS2k2OCB;IECuO|gxPSEQvF2u M1e0bFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7MUO2OFY2Lz5{OUGzOlQ3PTxxYU6=
SK-N-AS NU\INGtlSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NVjrcVNOPzJiaILz NXXnb484SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDTT{1PNUGVIHPlcIx{KGW6cILld5Nqdmdid3ns[EB1gXCnIFXNUFQuSUyNIHHmeIVzKDd{IHjyd{BjgSCFZXzsWIl1\XJvR3zvJGx2dWmwZYPj[Y51KEOnbHygWoli[mmuaYT5JGF{e2G7LDDFR|UxKD1iMT6wOFUh|ryPLh?= M1[3OFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NU[4Nlg6Lz5{NkW2PFI5QTxxYU6=
BAF3 M3nPe2N6fG:2b4jpZ4l1gSCjc4PhfS=> M4LXdVIhfG9iMzDkZZl{ MYfDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRWY{KGOnbHzzJIFnfGW{IEKgeI8hOyCmYYnzJIJ6KGy3Y3nm[ZJie2VicnXwc5J1\XJiZ3Xu[UBie3OjeTygTWM2OCB;IEKuOFc4KM7:TT6= MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd2MkK1Nkc,OjN5NEKyOVI9N2F-
Ba/F3 NXvIeopQTnWwY4Tpc44h[XO|YYm= NH3UO|E4OiCqcoO= MoS3TY5pcWKrdHnvckBw\iCHTVy0MWFNUyCOMUG1NnIhdXW2YX70JEh2dmuwb4fuJI9zcWerbjmg[ZhxemW|c3XkJIlvKG2xdYPlJGJiN0Z|IHPlcIx{KGG|c3Xzd4VlKGG|IHPlcIwhfmmjYnnsbZR6KGGodHXyJFczKGi{czDifUBOXFNiYYPzZZktKEmFNUCgQUAzNjd2NzFOwG0v M1;OcFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NU[4Nlg6Lz5{NkW2PFI5QTxxYU6=
BA/F3 MX;DfZRwfG:6aXPpeJkh[XO|YYm= NEjGd2s4OiCqcoO= MYLDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRU9HOyClZXzsd{Bie3Onc4Pl[EBieyClZXzsJJZq[WKrbHn0fUBi\nSncjC3NkBpenNiYomgUXRUKGG|c3H5MEBKSzVyIE2gOU42OTJizszNMi=> NInObpI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkW2PFI5QSd-Mk[1OlgzQDl:L3G+
KARPAS299 MlfjRZBweHSxc3nzJIF{e2G7 NGPGNIo3OCCwTR?= NYLRT4Y4OjRiaILz M2e1Vmlv\HWldHnvckBw\iCjcH;weI9{cXNiaX6gbJVu[W5iS1HSVGFUOjl7IHPlcIx{KGijcnLvdolv\yCQUF2tRWxMKGG2IE[wJI5OKGGodHXyJFI1KGi{czDifUBi[3KrZHnu[UBwemGwZ3Wv[ZRpcWSrdX2gZpJwdWmmZTDzeIFqdmmwZzDiZZNm\CCobIXvdoV{[2WwY3WgcYlkem:|Y3;wbYMhdWW2aH;k MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTF5NEiwPUc,OjlzN{S4NFk9N2F-
SU-DHL1 M3jjR2Z2dmO2aX;uJIF{e2G7 M{Ltc|IxKHSxIEKwNEBvVQ>? M3LiTFEhcHJ? MonQTY5pcWKrdHnvckBw\iCDTFugbY4hcHWvYX6gV3UuTEiOMTDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gbY4hW1SDVEOgdIhwe3Cqb4L5cIF1cW:wIHH0JHk4ODVicnXzbYR2\SCjdDCyNEB1dyB{MECgcm0h[W[2ZYKgNUBpeiCkeTDX[ZN1\XKwIHLsc5Qh[W6jbInzbZM> M4TNOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7Mki4PVQxLz5{OUK4PFk1ODxxYU6=
SU-DHL1 NW\TbVVQTnWwY4Tpc44h[XO|YYm= NX;wXmZiOjBidH:gNlAxKG6P NFHWUnUyKGi{ M2\wcGlvcGmkaYTpc44hd2ZiQVzLJJBpd3OyaH;yfYxifGmxbjDheEB[OTJ5ODDy[ZNq\HWnIHnuJIh2dWGwIGPVMWRJVDFiY3XscJMh[XRiMkCgeI8hOjByIH7NJIFnfGW{IEGgbJIh[nliV3XzeIVzdiCkbH;0JIFv[Wy7c3nz NH76SoQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUK4PFk1OCd-MkmyPFg6PDB:L3G+
NCI-H3122 NUfDe41pTnWwY4Tpc44h[XO|YYm= Mm[3NlAhfG9iMkCwJI5O NHjIfHYyKGi{ NYi2ZlQyUW6qaXLpeIlwdiCxZjDBUGshcW5iaIXtZY4hVkOLLVizNVIzKGOnbHzzJIF{e2W|c3XkJIF{KHKnZIXjeIlwdiCrbjDFVmsheGixc4Doc5J6dGG2aX;uJIF1KFR{MEKvM3kzODRicnXzbYR2\XNiYYSgNlAhfG9iMkCwJI5OKGGodHXyJFEhcHJiYomgW4V{fGW{bjDicI91KGGwYXz5d4l{ MnHEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl{OEi5OFAoRjJ7Mki4PVQxRC:jPh?=
NCI-H3122 MkLLSpVv[3Srb36gZZN{[Xl? M2f5d|IxKHSxIEKwNEBvVQ>? NFHyPXoyKGi{ MWfJcohq[mm2aX;uJI9nKEGOSzDpckBpfW2jbjDOR2kuUDNzMkKgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKEGtdDDwbI9{eGixconsZZRqd25iYYSgV|Q4OyC{ZYPp[JVmKGG2IEKwJJRwKDJyMDDuUUBi\nSncjCxJIhzKGK7IGfld5Rmem5iYnzveEBidmGueYPpdy=> NHPGeVE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUK4PFk1OCd-MkmyPFg6PDB:L3G+
SU-DHL1 M4[wbmZ2dmO2aX;uJIF{e2G7 MoXVNlAhfG9iMkCwJI5O MXKxJIhz M1e3UmlvcGmkaYTpc44hd2ZiQVzLJIlvKGi3bXHuJHNWNUSKTEGgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKEGtdDDwbI9{eGixconsZZRqd25iYYSgV|Q4OyC{ZYPp[JVmKGG2IEKwJJRwKDJyMDDuUUBi\nSncjCxJIhzKGK7IGfld5Rmem5iYnzveEBidmGueYPpdy=> NX3ieIxuRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmyPFg6PDBpPkK5Nlg5QTRyPD;hQi=>
SU-DHL1 NYfsTnd{TnWwY4Tpc44h[XO|YYm= NFTL[2IzOCC2bzCyNFAhdk1? MmLiNUBpeg>? NGDFfndKdmirYnn0bY9vKG:oIFHMT{BqdiCqdX3hckBUXS2GSFyxJINmdGy|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiCHUlugdIhwe3Cqb4L5cIF1cW:wIHH0JHQzODJxL2myNFQhemW|aXT1[ZMh[XRiMkCgeI8hOjByIH7NJIFnfGW{IEGgbJIh[nliV3XzeIVzdiCkbH;0JIFv[Wy7c3nz NYDVbJU1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmyPFg6PDBpPkK5Nlg5QTRyPD;hQi=>
NCI-H3122 M1jsV2Z2dmO2aX;uJIF{e2G7 MYSyNEB1dyB{MECgcm0> MWSxJIhz MXvJcohq[mm2aX;uJI9nKEGOSzDwbI9{eGixconsZZRqd25iYYSgXVEzPzhicnXzbYR2\SCrbjDoeY1idiCQQ1mtTFMyOjJiY3XscJMh[XRiMkCgeI8hOjByIH7NJIFnfGW{IEGgbJIh[nliV3XzeIVzdiCkbH;0JIFv[Wy7c3nz NEH3Z489[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUK4PFk1OCd-MkmyPFg6PDB:L3G+
NCI-H3122 MYTGeY5kfGmxbjDhd5NigQ>? NInMSmEzOCC2bzCyNFAhdk1? NUHmb2dpOSCqch?= NFjxZ5ZKdmirYnn0bY9vKG:oIFHMT{BqdiCqdX3hckBPS0lvSEOxNlIh[2WubIOgZZN{\XO|ZXSgZZMhemWmdXP0bY9vKGmwIGPURXQ{KHCqb4PwbI9zgWyjdHnvckBifCC\N{C1JJJme2mmdXWgZZQhOjBidH:gNlAxKG6PIHHmeIVzKDFiaIKgZpkhX2W|dHXyckBjdG:2IHHuZYx6e2m| MoHOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl{OEi5OFAoRjJ7Mki4PVQxRC:jPh?=
SU-DHL1 MlzSSpVv[3Srb36gZZN{[Xl? NUT1cXR1OzBibl2= NFnWSWQyPiCqcoO= M3jGO2lvcGmkaYTpc44hd2ZiQVzLJIF2fG:yaH;zdIhwenmuYYTpc44h[XRiWUG1NFchemW|aXT1[UBqdiCqdX3hckBUXS2GSFyxJINmdGy|IHH0JFMxKG6PIHHmeIVzKDF4IHjyd{BjgSCZZYP0[ZJvKGKub4SgZY5idHm|aYO= NWHje|Q1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm2Nlc4OjVpPkK5OlI4PzJ3PD;hQi=>
SU-DHL1 M2TaeWZ2dmO2aX;uJIF{e2G7 MWGzNEBvVQ>? NGexdFUyPiCqcoO= MmHrTY5pcWKrdHnvckBw\iCDTFugbY4hcHWvYX6gV3UuTEiOMTDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gbY4hW1SDVEOgdIhwe3Cqb4L5cIF1cW:wIHH0JHk4ODVicnXzbYR2\SCjdDCzNEBvVSCjZoTldkAyPiCqcoOgZpkhX2W|dHXyckBjdG:2IHHuZYx6e2m| M1Ow[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NkK3O|I2Lz5{OU[yO|czPTxxYU6=
NCI-H3122 MUDGeY5kfGmxbjDhd5NigQ>? NYrZUmx3PTBidH:gNlUxKG6P NFSxO4IyPiCqcoO= MULJcoR2[3Srb36gc4YhSUyNIHTl[5Ji\GG2aX;uJIlvKGi3bXHuJG5EUS2KM{GyNkBk\WyuczDhd5Nme3OnZDDhd{Bl\WO{ZXHz[UBqdiCDTFugdIhwe3Cqb4L5cIF1cW:wIHH0JHkyPjB2IHH0JFUxKHSxIEK1NEBvVSCjZoTldkAyPiCqcoOgZpkhcW2vdX7vZoxwfCCvZYToc4Q> NX7iNIVNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm2OlA6QDRpPkK5OlYxQTh2PD;hQi=>
SH-SY5Y NIqzbpdCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MVe3NkBpenN? M1HD[2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iU1itV3k2YSClZXzsd{Bi\nSncjC3NkBpenNiYomgR4VtdFSrdHXyMWdtdyCudX3pcoV{[2WwdDDj[YxtKH[rYXLpcIl1gSCjc4PhfS=> MlXOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl4NkC5PFQoRjJ7Nk[wPVg1RC:jPh?=
CHLA20 NXvvSHFGSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NUXVR3pWPzJiaILz M4HVN2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iQ1jMRVIxKGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDD[YxtXGm2ZYKtS4xwKGy3bXnu[ZNk\W62IHPlcIwhfmmjYnnsbZR6KGG|c3H5 MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTZ4MEm4OEc,Ojl4NkC5PFQ9N2F-
SH-SY5Y NX75OpRLSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NYnxO5NpPzJiaILz MnH6RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCVSD3TXVV[KGOnbHzzJIFnfGW{IEeyJIhzeyCrbjDwdoV{\W6lZTDv[kBCSkOEMTDpcohq[mm2b4KgeIFzcXG3aXThdkBjgSCFZXzsWIl1\XJvR3zvJIx2dWmwZYPj[Y51KGOnbHygeoli[mmuaYT5JIF{e2G7 M{\nPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7Nk[wPVg1Lz5{OU[2NFk5PDxxYU6=
KARPAS299 MmmzSpVv[3Srb36gZZN{[Xl? MmfwOVAhfG9iMkWwJI5O NWjzXpBEOTZiaILz NVPQcmpjUW6mdXP0bY9vKG:oIFHMT{Bl\We{YXTheIlwdiCrbjDoeY1idiCNQWLQRXMzQTliY3XscJMh[XO|ZYPz[YQh[XNiZHXjdoVie2ViaX6gRWxMKHCqb4PwbI9zgWyjdHnvckBifCC\MU[wOEBifCB3MDD0c{AzPTBibl2gZYZ1\XJiMU[gbJJ{KGK7IHntcZVvd2Kub4SgcYV1cG:m MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTZ4MEm4OEc,Ojl4NkC5PFQ9N2F-
CHLA20 NYraSZZLSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= MVi3NkBpenN? NVvBW3kzSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDDTGxCOjBiY3XscJMh[W[2ZYKgO|IhcHK|IHnuJJBz\XOnbnPlJI9nKEGEQ1KxJIlvcGmkaYTvdkB1[XKrcYXp[IFzKGK7IFPlcIxVcXSncj3HcI8hdHWvaX7ld4NmdnRiY3XscEB3cWGkaXzpeJkh[XO|YYm= MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTZ4MEm4OEc,Ojl4NkC5PFQ9N2F-
NCI-H3122 MVXBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? M4Psb|czKGi{cx?= NVLj[ZlkSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDOR2kuUDNzMkKgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KEOnbHzUbZRmei2JbH:gcJVucW6nc3PlcpQh[2WubDD2bYFjcWyrdImgZZN{[Xl? MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTZ4MEm4OEc,Ojl4NkC5PFQ9N2F-
KARPAS299 NHX0[5ZCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MYW3NkBpenN? M{LXVGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iS1HSVGFUOjl7IHPlcIx{KGGodHXyJFczKGi{czDifUBE\WyuVHn0[ZIuT2yxIHz1cYlv\XOlZX70JINmdGxidnnhZoltcXS7IHHzd4F6 MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTZ4MEm4OEc,Ojl4NkC5PFQ9N2F-
SU-DHL1 M1\CN2FvfGmycn;sbYZmemG2aY\lJIF{e2G7 M{LqWVczKGi{cx?= NE\ldXFCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGPVMWRJVDFiY3XscJMh[W[2ZYKgO|IhcHK|IHL5JGNmdGyWaYTldk1IdG9ibIXtbY5me2OnboSgZ4VtdCC4aXHibYxqfHliYYPzZZk> MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTZ4MEm4OEc,Ojl4NkC5PFQ9N2F-
KARPAS299 MnXKRZBweHSxc3nzJIF{e2G7 MoTLOVAhdk1? M1O2RlI1KGi{cx?= MW\JcoR2[3Srb36gc4Yh[XCxcITvd4l{KGmwIHj1cYFvKEuDUmDBV|I6QSClZXzsd{Bie3Onc4Pl[EBieyC3bnPs[YFzKGOnbHygd4hzcW6tYXflJIF1KDVyIH7NJIFnfGW{IEK0JIhzeyCkeTDIc4VkcHO2IEOzNlU5KHO2YXnubY5oKGKjc3XkJIlvfmW{dHXkJIZtfW:{ZYPj[Y5k\SCvaXPyc5Nkd3C7 M3jacFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMkKzNVIxLz5|MEKyN|EzODxxYU6=
KARPAS299 MWrBdI9xfG:|aYOgZZN{[Xl? NITmU2U2OCCwTR?= MXuyOEBpenN? M3XRW2lv\HWldHnvckBw\iCjcH;weI9{cXNiaX6gbJVu[W5iS1HSVGFUOjl7IHPlcIx{KGG|c3Xzd4VlKGG|IHzheIUh[XCxcITveIlkKGOnbHzzJIF1KDVyIH7NJIFnfGW{IEK0JIhzeyCkeTDBU{9GSiCmb4XicIUhe3SjaX7pcoch[mG|ZXSgbY53\XK2ZXSg[ox2d3Knc3PlcoNmKG2rY4Lvd4NweHl? MkTlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB{MkOxNlAoRjNyMkKzNVIxRC:jPh?=
KARPAS299 MXvBdI9xfG:|aYOgZZN{[Xl? NXTMfWE1PTBibl2= Mk\uNlQhcHK| M{DobGlv\HWldHnvckBw\iCjcH;weI9{cXNiaX6gbJVu[W5iS1HSVGFUOjl7IHPlcIx{KGG|c3Xzd4VlKGG|IH\yZYdu\W62YYTpc44h[XRiNUCgcm0h[W[2ZYKgNlQhcHK|IHL5JGhw\WOqc4SgN|MzPThic4ThbY5qdmdiYnHz[YQhcW64ZYL0[YQh\my3b4Lld4NmdmOnIH3pZ5Jwe2OxcIm= M{LOOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMkKzNVIxLz5|MEKyN|EzODxxYU6=

... 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
In vivo LDK378 is designed to reduce the possibility of forming reactive metabolites and shows undetectable levels of glutathione (GSH) adducts (<1%) in liver microsomes. LDK378 has relatively good metabolic stability, with moderate CYP3A4 (Midazolam substrate) inhibition and hERG inhibition. LDK378 exhibits low plasma clearance in animals (mouse, rat, dog and monkey) compared to liver blood flow, with the oral bioavailability of above 55% in mouse, rat, dog and monkey. LDK378 induces a dose-dependent growth inhibition and tumor regression in the Karpas299 and H2228 rat xenograft models, with no body-weight loss. LDK378 shows no impact on insulin levels or plasma glucose utilization in the mouse upon chronic dosing up to 100 mg/kg. [1]

Protocol

Kinase Assay:[1]
- Collapse

Enzymatic kinase profiling description:

All kinases are expressed as either Histidine- or GST-tagged fusion proteins using the baculovirus expression technology except for the untagged ERK2 which is produced in E. coli. The kinase activity is measured in the LabChip mobility shift assay. The assay is performed at 30°C for 60 min. The effect of LDK378 on the enzymatic activity is obtained from the linear progress curves in the absence and presence of LDK378 and routinely determines from one reading (end point measurement)
Cell Research:[1]
- Collapse
  • Cell lines: Ba/F3-NPM-ALK, Ba/F3-Tel-InsR, Ba/F3-WT, Karpas299 cells
  • Concentrations: ~100 μM
  • Incubation Time: 2-3 days
  • Method: Luciferase-expressing cells are incubated with serial dilutions of LDK378 or DMSO for 2-3 days. Luciferase expression is used as a measure of cell proliferation/survival and is evaluated with the Bright-Glo Luciferase Assay System. IC50 values are generated by using XLFit software.
    (Only for Reference)
Animal Research:[1]
- Collapse
  • Animal Models: RNU nude rats bearing the Karpas299/H2228 tumors
  • Dosages: ~50 mg/kg
  • Administration: Oral gavage
    (Only for Reference)

Solubility (25°C)

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

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 558.14
Formula

C28H36ClN5O3S

CAS No. 1032900-25-6
Storage powder
in solvent
Synonyms N/A
Smiles CC1=CC(=C(C=C1C2CCNCC2)OC(C)C)NC3=NC=C(C(=N3)NC4=CC=CC=C4S(=O)(=O)C(C)C)Cl

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
CalculateReset

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • 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):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

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

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

  • * Indicates a Required Field

Frequently Asked Questions

  • Question 1:

    how to reconstitute the inhibitor for oral administration to mice?

  • Answer:

    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

Related ALK Products

Tags: buy Ceritinib (LDK378) | Ceritinib (LDK378) supplier | purchase Ceritinib (LDK378) | Ceritinib (LDK378) cost | Ceritinib (LDK378) manufacturer | order Ceritinib (LDK378) | Ceritinib (LDK378) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID