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) M2DIeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVvyRm1IPzJiaB?= NF3oUmNFVVOR NWLlNph5UUN3ME2xOVg3KMLzIEG3N{BvVQ>? NIHMS2g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe0PVA{PCd-MkW3OFkxOzR:L3G+
WT 70 NEf2TIRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGfyW444OiCq NFrrSJNFVVOR NGGzdWhKSzVyPUKxJOKyKDhibl2= MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd2OUCzOEc,OjV5NEmwN|Q9N2F-
G1128S 1022 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHHBW4w4OiCq NV3h[4tXTE2VTx?= NVP1bnlwUUN3ME2xNFIhyrFiM{igcm0> NGHWU3o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe0PVA{PCd-MkW3OFkxOzR:L3G+
C1156F 1293 MljIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2XSXFczKGh? NF\Vb25FVVOR NYG5NFR5UUN3ME2yNVchyrFiMUG1JI5O MnLaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5NEmwN|QoRjJ3N{S5NFM1RC:jPh?=
I1171N 519 NEX1dFhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXq3NkBp NXHC[Vc5TE2VTx?= MX;JR|UxRTF6NzFCtUA5PyCwTR?= Mof4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5NEmwN|QoRjJ3N{S5NFM1RC:jPh?=
I1171T 445 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVi3NkBp NULwR2NkTE2VTx?= NH7RPHlKSzVyPUiyJOKyKDF{IH7N MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd2OUCzOEc,OjV5NEmwN|Q9N2F-
F1174I 184 NGLqUodIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1jwW|czKGh? MnXJSG1UVw>? NV;nbZRQUUN3ME2xN{DDuSByLkGgcm0> NIHrT4M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe0PVA{PCd-MkW3OFkxOzR:L3G+
N1178H 169 M1fMfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{\MdVczKGh? MoPCSG1UVw>? MV3JR|UxRTR{INMxJFYhdk1? M3H1eVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{S5NFM1Lz5{NUe0PVA{PDxxYU6=
E1210K 748 NWf6OGRXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2nHOFczKGh? NXr6RWc1TE2VTx?= NELLd2xKSzVyPUG4O{DDuSB6NDDuUS=> M4nOfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{S5NFM1Lz5{NUe0PVA{PDxxYU6=
C1156F/D1203N 2809 NHPjSVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYHab5duPzJiaB?= MnLySG1UVw>? M{HQdmlEPTB;MkW0JOKyKDl7IH7N MnG2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5NEmwN|QoRjJ3N{S5NFM1RC:jPh?=
Ba/F3 NA WT NFPSNIJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXW3NkBp MXrJR|UxRTBwMEKwJO69VQ>? NHfQeoQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyO|QxOCd-MkW3Nlc1ODB:L3G+
Ba/F3 NA C1156Y NW\N[2R6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmXkO|IhcA>? NVXHd491UUN3ME2wMlA4OSEQvF2= MmXjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5Mke0NFAoRjJ3N{K3OFAxRC:jPh?=
Ba/F3 NA L1196M M13XN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mo\vO|IhcA>? M3rRZmlEPTB;MD6wOFIh|ryP MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd{N{SwNEc,OjV5Mke0NFA9N2F-
Ba/F3 NA L1152R M4fOUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnjNO|IhcA>? NGDPWpVKSzVyPUCuNlg5KM7:TR?= NHjqcoc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyO|QxOCd-MkW3Nlc1ODB:L3G+
Ba/F3 NA G1202R MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXywbmNuPzJiaB?= MUnJR|UxRTBwMke3JO69VQ>? MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd{N{SwNEc,OjV5Mke0NFA9N2F-
Ba/F3 NA G1269A M1;w[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWm5bGp7PzJiaB?= M2T1WmlEPTB;MD6wNVkh|ryP MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd{N{SwNEc,OjV5Mke0NFA9N2F-
Ba/F3 NA S1206Y NIT0NpJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXi3NkBp MUPJR|UxRTBwMEO3JO69VQ>? NHvsUlk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyO|QxOCd-MkW3Nlc1ODB:L3G+
Ba/F3 EA WT MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4nm[FczKGh? M37m[WlEPTB;MD6wNlEh|ryP NX\lb|YzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3Nlc1ODBpPkK1O|I4PDByPD;hQi=>
Ba/F3 EA C1156Y NFfT[HRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHHkbYM4OiCq NF:xbGVKSzVyPUCuNFI3KM7:TR?= NXe2W3I5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3Nlc1ODBpPkK1O|I4PDByPD;hQi=>
Ba/F3 EA L1196M Mn74S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4rodlczKGh? MnrmTWM2OD1yLkCxPUDPxE1? MmXVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5Mke0NFAoRjJ3N{K3OFAxRC:jPh?=
Ba/F3 EA L1152R NYjMSmhsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVL6UmJiPzJiaB?= MlrUTWM2OD1yLkC5PUDPxE1? NHnNfYY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyO|QxOCd-MkW3Nlc1ODB:L3G+
Ba/F3 EA G1202R M{XUZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUPYfHN[PzJiaB?= M1jOVGlEPTB;MD60Olch|ryP MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd{N{SwNEc,OjV5Mke0NFA9N2F-
Ba/F3 EA G1269A NVrMW4ZyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MknRO|IhcA>? M4P2VmlEPTB;MD6wN|Mh|ryP M{D4[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{K3OFAxLz5{NUeyO|QxODxxYU6=
Ba/F3 EA S1206Y MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFrIW3I4OiCq M3fxZmlEPTB;MD6wN|gh|ryP NGK2SJQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUeyO|QxOCd-MkW3Nlc1ODB:L3G+
BAF3 NUfleJRoSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= NYSxb4RkPzJiaILz M2Lzb2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgcY92e2ViQlHGN{Bk\WyuczDoZZJjd3KrbnegSW1NPC2DTFugZYZ1\XJiN{KgbJJ{KGK7IGPSRkBweiCFQ1u4JIF{e2G7LDDJR|UxKD1iMD6wNVA4KM7:TT6= MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTJ6OEm0NEc,Ojl{OEi5OFA9N2F-
NCI-H3122 M{TwTGFvfGmycn;sbYZmemG2aY\lJIF{e2G7 MVO3NkBpenN? M4rEbGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTlPJMWg{OTJ{IHPlcIx{KGGodHXyJFczKGi{czDifUBE\WyuVHn0[ZIuT2yxIFz1cYlv\XOlZX70JGNmdGxiVnnhZoltcXS7IFHzd4F6NCCHQ{WwJF0hOC5yMUWg{txONg>? M3vTNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NU[4Nlg6Lz5{NkW2PFI5QTxxYU6=
NCI-H2228 NULV[GdOT3Kxd4ToJIlvcGmkaYTpc44h[XO|YYm= NVexOIxFOyCmYYnz Ml6yS5Jwf3SqIHnubIljcXSrb36gc4YhcHWvYX6gUmNKNUh{MkK4JINmdGy|IHHmeIVzKDNiZHH5d{BjgSCudX3pcoV{[2WwY3WtZoF{\WRiQ3XscHRqfGW{LVfsc{Bie3OjeTygTWM2OCB;IECuNFE2KM7:TT6= MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTZ{N{eyOUc,Ojl4Mke3NlU9N2F-
SU-DHL1 NGrjO4pIem:5dHigbY5pcWKrdHnvckBie3OjeR?= MYqzJIRigXN? Mmq0S5Jwf3SqIHnubIljcXSrb36gc4YhcHWvYX6gV3UuTEiOMTDj[YxteyCjZoTldkA{KGSjeYOgZpkhdHWvaX7ld4NmdmOnLXLhd4VlKEOnbHzUbZRmei2JbH:gZZN{[XluIFnDOVAhRSByLkCxOUDPxE1w NGe0OmU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OU[yO|czPSd-Mkm2Nlc4OjV:L3G+
DFCI114 MX\BcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? NFyySGM4OiCqcoO= M4XQUmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iRF\DTVEyPCClZXzsd{BmgHC{ZYPzbY5oKEWPTEStRWxMKEdzMk[5RUBufXSjboSgZYZ1\XJiN{KgbJJ{KGK7IFPlcIxVcXSncj3HcI8hVHWvaX7ld4NmdnRiQ3XscEBXcWGkaXzpeJkhSXO|YYmsJGVEPTBiPTCwMlAyQCEQvF2u NHfhV3A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkW2PFI5QSd-Mk[1OlgzQDl:L3G+
HCC78 Mn7nR5l1d3SxeHnjbZR6KGG|c3H5 NHG1OYc4OiCqcoO= MW\DfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDIR2M4QCClZXzsd{Bp[XKkb4LpcochW0yFM{TBNk1TV1NzIHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiClZXzsJJBzd2yrZnXyZZRqd25iYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NEA:KDBwMEG4JO69VS5? MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzR5NEmyOUc,Ojd2N{S5NlU9N2F-
KARPAS299 NVPOUYl5S3m2b4TvfIlkcXS7IHHzd4F6 MWOyJJRwKDNiZHH5dy=> MVfDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDLRXJRSVN{OUmgZ4VtdHNiYX\0[ZIhOiC2bzCzJIRigXNiYomgcJVkcW[ncnHz[UBz\XCxcoTldkBo\W6nIHHzd4F6NCCLQ{WwJF0hOC5yMkK4JO69VS5? NIPwNlU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{e0NlI2Oid-MkO3OFIzPTJ:L3G+
KARPAS299 NGS3UHpEgXSxdH;4bYNqfHliYYPzZZk> MorBR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gT2FTWEGVMkm5JINmdGy|IHX4dJJme3OrbnegUnBONUGOSzDmeZNqd25iZ3Xu[UBie3Onc4Pl[EBieyCpcn;3eIghcW6qaXLpeIlwdixiSVO1NEA:KDBwMEKyPEDPxE1w NUC2RYUyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO4N|c4QTdpPkKzPFM4Pzl5PD;hQi=>
NCI-H3122 M2HtSmZ2dmO2aX;uJIF{e2G7 NFvGWY84OiCqcoO= NYPjdWZCUW6qaXLpeIlwdiCxZjDFUWw1KG[3c3XkJGFNUyCrbjDoeY1idiCQQ1mtTFMyOjJiY3XscJMh[XO|ZYPz[YQh[XNiY3XscEBoem:5dHigbY5pcWKrdHnvckBu\WG|dYLl[EBi\nSncjC3NkBpenNiYomgV3JDKGG|c3H5MEBESzVyIE2gNE4xOjVizszNMi=> M1niUlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5OUG1NVY6Lz5{N{mxOVE3QTxxYU6=
BAF3 NWHqSpdCTnWwY4Tpc44h[XO|YYm= MoC0NkB1dyB|IHThfZM> MWTJcohq[mm2aX;uJI9nKE6STT3meZNm\CCDTFugLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO|ZXSgbY4hdW:3c3WgRmFHOyClZXzsd{Bi\nSncjCyJJRwKDNiZHH5d{BjgSCudXPp[oVz[XOnIILldI9zfGW{IHflcoUh[XO|YYmsJGlEPTBiPTCwMlAzPiEQvF2u MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd2MkK1Nkc,OjN5NEKyOVI9N2F-
BA/F3 MXrDfZRwfG:6aXPpeJkh[XO|YYm= NF7Pb2xEgXSxdH;4bYNqfHliYXfhbY5{fCCvb4Xz[UBDSS:IMzDj[YxteyCneIDy[ZN{cW6pIF7QUU1CVEtiZoXzbY9vKGenbnWgZZN{\XO|ZXSgZZMh\3Kxd4ToJIlvcGmkaYTpc44tKEmFNUCgQUAxNjB{NjFOwG0v M{nEblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|OEO3O|k4Lz5{M{izO|c6PzxxYU6=
KARPAS299 M3TGUmFvfGmycn;sbYZmemG2aY\lJIF{e2G7 MmW5O|IhcHK| Mlu2RY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCNQWLQRXMzQTliY3XscJMhcGG{Yn;ybY5oKE6STT3BUGsh[W[2ZYKgO|IhcHK|IHL5JG1VXCCjc4PhfUwhUUN3MDC9JFAvODJ4IN88UU4> MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTF5NEiwPUc,OjlzN{S4NFk9N2F-
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CHLA20 MUXBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? MV[3NkBpenN? MljuRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCFSFzBNlAh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IFPlcIxVcXSncj3HcI8hdHWvaX7ld4NmdnRiY3XscEB3cWGkaXzpeJkh[XO|YYm= NWXrOXk2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm2OlA6QDRpPkK5OlYxQTh2PD;hQi=>
SH-SY5Y M4nP[WFvfGmycn;sbYZmemG2aY\lJIF{e2G7 M{nzbFczKGi{cx?= M2XLOWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iU1itV3k2YSClZXzsd{Bi\nSncjC3NkBpenNiaX6gdJJme2WwY3Wgc4YhSUKFQkGgbY5pcWKrdH;yJJRiemmzdXnkZZIh[nliQ3XscHRqfGW{LVfsc{BtfW2rbnXzZ4VvfCClZXzsJJZq[WKrbHn0fUBie3OjeR?= M1\yPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7Nk[wPVg1Lz5{OU[2NFk5PDxxYU6=
KARPAS299 Mm\xSpVv[3Srb36gZZN{[Xl? MoLwOVAhfG9iMkWwJI5O M{K4UlE3KGi{cx?= M{XIWmlv\HWldHnvckBw\iCDTFug[IVoemGmYYTpc44hcW5iaIXtZY4hU0GUUFHTNlk6KGOnbHzzJIF{e2W|c3XkJIF{KGSnY4LlZZNmKGmwIFHMT{BxcG:|cHjvdplt[XSrb36gZZQhYTF4MESgZZQhPTBidH:gNlUxKG6PIHHmeIVzKDF4IHjyd{BjgSCrbX31co9jdG:2IH3leIhw\A>? MoPOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl4NkC5PFQoRjJ7Nk[wPVg1RC:jPh?=
CHLA20 NXroPIloSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= M3r5N|czKGi{cx?= Ml7mRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCFSFzBNlAh[2WubIOgZYZ1\XJiN{KgbJJ{KGmwIIDy[ZNmdmOnIH;mJGFDS0JzIHnubIljcXSxcjD0ZZJqeXWrZHHyJIJ6KEOnbHzUbZRmei2JbH:gcJVucW6nc3PlcpQh[2WubDD2bYFjcWyrdImgZZN{[Xl? NH;WcIo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OU[2NFk5PCd-Mkm2OlA6QDR:L3G+
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KARPAS299 NGSwVoNCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MmHNO|IhcHK| MXrBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEuDUmDBV|I6QSClZXzsd{Bi\nSncjC3NkBpenNiYomgR4VtdFSrdHXyMWdtdyCudX3pcoV{[2WwdDDj[YxtKH[rYXLpcIl1gSCjc4PhfS=> M3;0c|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7Nk[wPVg1Lz5{OU[2NFk5PDxxYU6=
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KARPAS299 MlPORZBweHSxc3nzJIF{e2G7 MXu1NEBvVQ>? MVGyOEBpenN? NFPRbG9KdmS3Y4Tpc44hd2ZiYYDvdJRwe2m|IHnuJIh2dWGwIFvBVnBCWzJ7OTDj[YxteyCjc4Pld5Nm\CCjczDsZZRmKGGyb4D0c5Rq[yClZXzsd{BifCB3MDDuUUBi\nSncjCyOEBpenNiYomgRW8wTUJiZH;1ZoxmKHO2YXnubY5oKGKjc3XkJIlvfmW{dHXkJIZtfW:{ZYPj[Y5k\SCvaXPyc5Nkd3C7 MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODJ{M{GyNEc,OzB{MkOxNlA9N2F-
KARPAS299 MmC4RZBweHSxc3nzJIF{e2G7 MVu1NEBvVQ>? NHvFbGozPCCqcoO= NYm3NIE1UW6mdXP0bY9vKG:oIHHwc5B1d3OrczDpckBpfW2jbjDLRXJRSVN{OUmgZ4VtdHNiYYPz[ZN{\WRiYYOg[pJi\22nboTheIlwdiCjdDC1NEBvVSCjZoTldkAzPCCqcoOgZpkhUG:nY3jzeEA{OzJ3ODDzeIFqdmmwZzDiZZNm\CCrbo\ldpRm\CCobIXvdoV{[2WwY3WgcYlkem:|Y3;wfS=> NXm4cINERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CyNlMyOjBpPkOwNlI{OTJyPD;hQi=>
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 2022-08-01)

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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