Ceritinib (LDK378)

Catalog No.S7083

For research use only.

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.

Ceritinib (LDK378) Chemical Structure

CAS No. 1032900-25-6

Selleck's Ceritinib (LDK378) has been cited by 88 publications

Purity & Quality Control

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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) Mmn3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGLFc2k4OiCq NIPNRmFFVVOR NE\pW|FKSzVyPUG1PFYhyrFiMUezJI5O NGHYU289[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe0PVA{PCd-MkW3OFkxOzR:L3G+
WT 70 NIm0bJhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFjj[nI4OiCq M4WzT2ROW09? Ml\VTWM2OD1{MTFCtUA5KG6P M1vOfVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{S5NFM1Lz5{NUe0PVA{PDxxYU6=
G1128S 1022 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFjmVHc4OiCq MWXEUXNQ M4XG[2lEPTB;MUCyJOKyKDN6IH7N MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd2OUCzOEc,OjV5NEmwN|Q9N2F-
C1156F 1293 MmT2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUPYXWw1PzJiaB?= NUHibVFjTE2VTx?= M{PCbGlEPTB;MkG3JOKyKDFzNTDuUS=> NWnPRXNYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3OFkxOzRpPkK1O|Q6ODN2PD;hQi=>
I1171N 519 NXnGVlJxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXvvPHFKPzJiaB?= Mn3ISG1UVw>? MoXtTWM2OD1zOEegxtEhQDdibl2= MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd2OUCzOEc,OjV5NEmwN|Q9N2F-
I1171T 445 NVzvN3QxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml\iO|IhcA>? MVHEUXNQ MX3JR|UxRTh{INMxJFEzKG6P MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd2OUCzOEc,OjV5NEmwN|Q9N2F-
F1174I 184 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVu5XGdRPzJiaB?= Mk[4SG1UVw>? NHfzfnFKSzVyPUGzJOKyKDBwMTDuUS=> MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd2OUCzOEc,OjV5NEmwN|Q9N2F-
N1178H 169 M4Hlcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXHBWpRQPzJiaB?= Mo\DSG1UVw>? MYnJR|UxRTR{INMxJFYhdk1? Mn;hQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5NEmwN|QoRjJ3N{S5NFM1RC:jPh?=
E1210K 748 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXq3NkBp MYPEUXNQ NH22dlhKSzVyPUG4O{DDuSB6NDDuUS=> MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd2OUCzOEc,OjV5NEmwN|Q9N2F-
C1156F/D1203N 2809 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1;zblczKGh? NXvUUWhuTE2VTx?= MUXJR|UxRTJ3NDFCtUA6QSCwTR?= MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd2OUCzOEc,OjV5NEmwN|Q9N2F-
Ba/F3 NA WT MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkC3O|IhcA>? NYHZNZJXUUN3ME2wMlAzOCEQvF2= NFi3dHg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyO|QxOCd-MkW3Nlc1ODB:L3G+
Ba/F3 NA C1156Y M4nVVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVKyTmNLPzJiaB?= M3\XcmlEPTB;MD6wO|Eh|ryP MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd{N{SwNEc,OjV5Mke0NFA9N2F-
Ba/F3 NA L1196M NXT3dW1jT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1myb|czKGh? MVTJR|UxRTBwMESyJO69VQ>? MmjVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5Mke0NFAoRjJ3N{K3OFAxRC:jPh?=
Ba/F3 NA L1152R MoTGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1vDPVczKGh? MUPJR|UxRTBwMki4JO69VQ>? NWHpdW5FRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3Nlc1ODBpPkK1O|I4PDByPD;hQi=>
Ba/F3 NA G1202R MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{HyfFczKGh? NGTkW25KSzVyPUCuNlc4KM7:TR?= NEW5fmQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyO|QxOCd-MkW3Nlc1ODB:L3G+
Ba/F3 NA G1269A NIf2ZXRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVzzXpp{PzJiaB?= NHjiVZFKSzVyPUCuNFE6KM7:TR?= MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd{N{SwNEc,OjV5Mke0NFA9N2F-
Ba/F3 NA S1206Y NEnTZ4lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVzvZVdUPzJiaB?= NGPjOopKSzVyPUCuNFM4KM7:TR?= MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd{N{SwNEc,OjV5Mke0NFA9N2F-
Ba/F3 EA WT NEHMdGlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFrMXVc4OiCq NHXRPWhKSzVyPUCuNFIyKM7:TR?= M1\uOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{K3OFAxLz5{NUeyO|QxODxxYU6=
Ba/F3 EA C1156Y NYSzdWk4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUTG[VJiPzJiaB?= MVPJR|UxRTBwMEK2JO69VQ>? M3XFTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{K3OFAxLz5{NUeyO|QxODxxYU6=
Ba/F3 EA L1196M NHr6VWtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIL2RmQ4OiCq M3\5[GlEPTB;MD6wNVkh|ryP MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd{N{SwNEc,OjV5Mke0NFA9N2F-
Ba/F3 EA L1152R NXXxcYZ5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFjocHc4OiCq NUnFfZRGUUN3ME2wMlA6QSEQvF2= M17wT|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{K3OFAxLz5{NUeyO|QxODxxYU6=
Ba/F3 EA G1202R NYXtTo9vT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnT0O|IhcA>? MYjJR|UxRTBwNE[3JO69VQ>? MlvpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5Mke0NFAoRjJ3N{K3OFAxRC:jPh?=
Ba/F3 EA G1269A MmnnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NILz[Jg4OiCq MXzJR|UxRTBwMEOzJO69VQ>? MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd{N{SwNEc,OjV5Mke0NFA9N2F-
Ba/F3 EA S1206Y M4SxSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGnKN3I4OiCq MoS5TWM2OD1yLkCzPEDPxE1? NFLzcHU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyO|QxOCd-MkW3Nlc1ODB:L3G+
BAF3 Mn\SRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? NETB[2s4OiCqcoO= NU\XUHV6SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBud3W|ZTDCRWY{KGOnbHzzJIhiemKxcnnu[{BGVUx2LVHMT{Bi\nSncjC3NkBpenNiYomgV3JDKG:{IFPDT|gh[XO|YYmsJGlEPTBiPTCwMlAyODdizszNMi=> M1zjUlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7Mki4PVQxLz5{OUK4PFk1ODxxYU6=
NCI-H3122 MoPDRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? NHv3ZXo4OiCqcoO= NGfaUXBCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF7DTU1JOzF{MjDj[YxteyCjZoTldkA4OiCqcoOgZpkhS2WubGTpeIVzNUeubzDMeY1qdmW|Y3XueEBE\WyuIG\pZYJqdGm2eTDBd5NigSxiRVO1NEA:KDBwMEG1JO69VS5? NFnrSpE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkW2PFI5QSd-Mk[1OlgzQDl:L3G+
NCI-H2228 M{jkPWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MnjLN{Bl[Xm| MYHHdo94fGhiaX7obYJqfGmxbjDv[kBpfW2jbjDOR2kuUDJ{MkigZ4VtdHNiYX\0[ZIhOyCmYYnzJIJ6KGy3bXnu[ZNk\W6lZT3iZZNm\CCFZXzsWIl1\XJvR3zvJIF{e2G7LDDJR|UxKD1iMD6wNVUh|ryPLh?= MknFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl4Mke3NlUoRjJ7NkK3O|I2RC:jPh?=
SU-DHL1 NVjWXFZqT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= M3nV[VMh\GG7cx?= NYHvephiT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hW1VvRFjMNUBk\WyuczDh[pRmeiB|IHThfZMh[nlibIXtbY5me2OnbnPlMYJie2WmIFPlcIxVcXSncj3HcI8h[XO|YYmsJGlEPTBiPTCwMlAyPSEQvF2u M4iwTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NkK3O|I2Lz5{OU[yO|czPTxxYU6=
DFCI114 NVfMV2JOSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NGLqb204OiCqcoO= MYjBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKESIQ1mxNVQh[2WubIOg[ZhxemW|c3nu[{BGVUx2LVHMT{BIOTJ4OVGgcZV1[W62IHHmeIVzKDd{IHjyd{BjgSCFZXzsWIl1\XJvR3zvJGx2dWmwZYPj[Y51KEOnbHygWoli[mmuaYT5JGF{e2G7LDDFR|UxKD1iMD6wNVgh|ryPLh?= NV\LUYg5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1OlgzQDlpPkK2OVY5Ojh7PD;hQi=>
HCC78 NYHzbll1S3m2b4TvfIlkcXS7IHHzd4F6 M2qxOlczKGi{cx?= M{i0PGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGhESzd6IHPlcIx{KGijcnLvdolv\yCVTFOzOGEzNVKRU{GgZZN{\XO|ZXSgZZMhemWmdXP0bY9vKGmwIHPlcIwheHKxbHnm[ZJifGmxbjDh[pRmeiB5MjDodpMh[nliTWTUJIF{e2G7LDDJR|UxKD1iMD6wNVgh|ryPLh?= NGHvV5U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{S3OFkzPSd-Mke0O|Q6OjV:L3G+
KARPAS299 NF\1Z5ZEgXSxdH;4bYNqfHliYYPzZZk> MnfTNkB1dyB|IHThfZM> NV2yXXJnS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hU0GUUFHTNlk6KGOnbHzzJIFnfGW{IEKgeI8hOyCmYYnzJIJ6KGy3Y3nm[ZJie2VicnXwc5J1\XJiZ3Xu[UBie3OjeTygTWM2OCB;IECuNFIzQCEQvF2u NE\4T3M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e0NlI2Oid-MkO3OFIzPTJ:L3G+
KARPAS299 NXfOWWtTS3m2b4TvfIlkcXS7IHHzd4F6 M3j6TGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGtCWlCDU{K5PUBk\WyuczDlfJBz\XO|aX7nJG5RVS2DTFug[pV{cW:wIHflcoUh[XO|ZYPz[YQh[XNiZ4Lve5RpKGmwaHnibZRqd25uIFnDOVAhRSByLkCyNlgh|ryPLh?= MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzh|N{e5O{c,OjN6M{e3PVc9N2F-
NCI-H3122 Mn7GSpVv[3Srb36gZZN{[Xl? MUS3NkBpenN? NXm1fVVCUW6qaXLpeIlwdiCxZjDFUWw1KG[3c3XkJGFNUyCrbjDoeY1idiCQQ1mtTFMyOjJiY3XscJMh[XO|ZYPz[YQh[XNiY3XscEBoem:5dHigbY5pcWKrdHnvckBu\WG|dYLl[EBi\nSncjC3NkBpenNiYomgV3JDKGG|c3H5MEBESzVyIE2gNE4xOjVizszNMi=> MlrCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd7MUWxOlkoRjJ5OUG1NVY6RC:jPh?=
BAF3 MWnGeY5kfGmxbjDhd5NigQ>? MV2yJJRwKDNiZHH5dy=> NH7FdGNKdmirYnn0bY9vKG:oIF7QUU1nfXOnZDDBUGshMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5ibX;1d4UhSkGIMzDj[YxteyCjZoTldkAzKHSxIEOg[IF6eyCkeTDseYNq\mW{YYPlJJJmeG:{dHXyJIdmdmViYYPzZZktKEmFNUCgQUAxNjB{NjFOwG0v M1:2eFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|N{SyNlUzLz5{M{e0NlI2OjxxYU6=
BA/F3 MofDR5l1d3SxeHnjbZR6KGG|c3H5 NXmwN5J[S3m2b4TvfIlkcXS7IHHnZYlve3RibX;1d4UhSkFxRkOgZ4VtdHNiZYjwdoV{e2mwZzDOVG0uSUyNIH\1d4lwdiCpZX7lJIF{e2W|c3XkJIF{KGe{b4f0bEBqdmirYnn0bY9vNCCLQ{WwJF0hOC5yMk[g{txONg>? Mk\1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN6M{e3PVcoRjJ|OEO3O|k4RC:jPh?=
KARPAS299 MUTBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? NGLNUYs4OiCqcoO= M1jTNGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iS1HSVGFUOjl7IHPlcIx{KGijcnLvdolv\yCQUF2tRWxMKGGodHXyJFczKGi{czDifUBOXFRiYYPzZZktKEmFNUCgQUAxNjB{NjFOwG0v Mlm5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjlzN{S4NFkoRjJ7MUe0PFA6RC:jPh?=
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SH-SY5Y M{XEcWFvfGmycn;sbYZmemG2aY\lJIF{e2G7 M1TKOlczKGi{cx?= MkjlRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCVSD3TXVV[KGOnbHzzJIFnfGW{IEeyJIhzeyCrbjDwdoV{\W6lZTDv[kBCSkOEMTDpcohq[mm2b4KgeIFzcXG3aXThdkBjgSCFZXzsWIl1\XJvR3zvJIx2dWmwZYPj[Y51KGOnbHygeoli[mmuaYT5JIF{e2G7 M1fac|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7Nk[wPVg1Lz5{OU[2NFk5PDxxYU6=
KARPAS299 NFLle49HfW6ldHnvckBie3OjeR?= M33FXFUxKHSxIEK1NEBvVQ>? MUGxOkBpenN? NVXsO|NMUW6mdXP0bY9vKG:oIFHMT{Bl\We{YXTheIlwdiCrbjDoeY1idiCNQWLQRXMzQTliY3XscJMh[XO|ZYPz[YQh[XNiZHXjdoVie2ViaX6gRWxMKHCqb4PwbI9zgWyjdHnvckBifCC\MU[wOEBifCB3MDD0c{AzPTBibl2gZYZ1\XJiMU[gbJJ{KGK7IHntcZVvd2Kub4SgcYV1cG:m NXrDTZgxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm2OlA6QDRpPkK5OlYxQTh2PD;hQi=>
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NCI-H3122 NV7ibmZRSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= M1exTlczKGi{cx?= NUDJRmVOSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDOR2kuUDNzMkKgZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KEOnbHzUbZRmei2JbH:gcJVucW6nc3PlcpQh[2WubDD2bYFjcWyrdImgZZN{[Xl? M2n4W|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7Nk[wPVg1Lz5{OU[2NFk5PDxxYU6=
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KARPAS299 NEL6WHpCeG:ydH;zbZMh[XO|YYm= M2fsT|UxKG6P NWHvU|FzOjRiaILz MUnJcoR2[3Srb36gc4Yh[XCxcITvd4l{KGmwIHj1cYFvKEuDUmDBV|I6QSClZXzsd{Bie3Onc4Pl[EBieyCocnHncYVvfGG2aX;uJIF1KDVyIH7NJIFnfGW{IEK0JIhzeyCkeTDIc4VkcHO2IEOzNlU5KHO2YXnubY5oKGKjc3XkJIlvfmW{dHXkJIZtfW:{ZYPj[Y5k\SCvaXPyc5Nkd3C7 M2DV[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMkKzNVIxLz5|MEKyN|EzODxxYU6=
Assay
Methods Test Index PMID
Western blot p-ALK / ALK / p-AKT / AKT / p-ERK / ERK ; pROS1 / ROS1 / pSTAT3 / STAT3 28425916 25351743
Growth inhibition assay Cell viability 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 (from reference)

Kinase Assay:[1]
  • 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]
  • 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.
Animal Research:[1]
  • Animal Models: RNU nude rats bearing the Karpas299/H2228 tumors
  • Dosages: ~50 mg/kg
  • Administration: Oral gavage

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 558.14
Formula

C28H36ClN5O3S

CAS No. 1032900-25-6
Storage 3 years -20°C powder
2 years -80°C in solvent
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)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

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

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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

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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.

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