Crizotinib (PF-02341066)

For research use only.

Licensed by Pfizer Catalog No.S1068

261 publications

Crizotinib (PF-02341066) Chemical Structure

Molecular Weight(MW): 450.34

Crizotinib (PF-02341066) is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM in cell-based assays, respectively. It is also a potent ROS1 inhibitor with Ki value less than 0.025 nM. Crizotinib induces autophagy through inhibition of the STAT3 pathway in multiple lung cancer cell lines.

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Selleck's Crizotinib (PF-02341066) has been cited by 261 publications

Purity & Quality Control

Choose Selective c-Met Inhibitors

Biological Activity

Description Crizotinib (PF-02341066) is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM in cell-based assays, respectively. It is also a potent ROS1 inhibitor with Ki value less than 0.025 nM. Crizotinib induces autophagy through inhibition of the STAT3 pathway in multiple lung cancer cell lines.
Targets
ROS1 [6]
(Cell-free assay)
c-Met [1]
(A549, MDA-MB-231, GTL-16, HT29, 786-O, Colo-205, A498 cells)
ALK [1]
(Karpas299 cells)
<0.025 nM(Ki) 11 nM 24 nM
In vitro

PF-2341066 displays similar potency against c-Met phosphorylation in mIMCD3 mouse or MDCK canine epithelial cells with IC50 of 5 nM and 20 nM, respectivly. PF-2341066 shows improved or similar activity against NIH3T3 cells engineered to express c-Met ATP-binding site mutants V1092I or H1094R or the P-loop mutant M1250T with IC50 of 19 nM, 2 nM and 15 nM, respectively, compared with NIH3T3 cells expressing wild-type receptor with IC50 of 13 nM. In contrast, a marked shift in potency of PF-2341066 is observed against cells engineered to express c-Met activation loop mutants Y1230C and Y1235D with IC50 of 127 nM and 92 nM, respectively, compared with wild-type receptor. PF-2341066 also potently prevents the phosphorylation of c-Met in NCI-H69 and HOP92 cells, with IC50 of 13 nM and 16 nM, respectively, which express the endogenous c-Met variants R988C and T1010I, respectively. PF-2341066 is >1,000-fold selective for the VEGFR2 and PDGFRβ RTKs, >250-fold selective for IRK and Lck, and ∼40- to 60-fold selective for Tie2, TrkA, and TrkB, all compared with c-Met. PF-2341066 is 20- to 30-fold selective for RON and Axl RTKs. In contrast, PF-2341066 shows a near-equivalent IC50 of 24 nM against the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) oncogenic fusion variant of the ALK RTK expressed by the KARPAS299 human anaplastic large cell lymphoma (ALCL) cell line. PF-2341066 inhibits c-Met–dependent neoplastic phenotypes of cancer cells and angiogenic phenotypes of endothelial cells. PF-2341066 suppresses human GTL-16 gastric carcinoma cell growth with IC50 of 9.7 nM. PF-2341066 induces apoptosis in GTL-16 cells with IC50 of 8.4 nM. PF-2341066 inhibits HGF-stimulated human NCI-H441 lung carcinoma cell migration and invasion with IC50 of 11 nM and 6.1 nM, respectively. PF-2341066 inhibits MDCK cell scattering with IC50 of 16 nM. PF-2341066 prevents HGF-stimulated c-Met phosphorylation, cell survival, and Matrigel invasion with IC50 of 11 nM, 14 nM and 35 nM, respectively. In addition, PF-2341066 prevents serum-stimulated HMVEC branching tubulogenesis (formation of vascular tubes) in fibrin gels. [1] PF-2341066 also potently inhibits NPM-ALK phosphorylation in Karpas299 or SU-DHL-1 ALCL cells with an IC50 of 24 nM. PF-2341066 potently prevents cell proliferation, which is associated with G(1)-S-phase cell cycle arrest and induction of apoptosis in ALK-positive ALCL cells with IC50 of 30 nM, but not ALK-negative lymphoma cells. [2] Besides, PF-2341066 prevents osteosarcoma behavior associated with primary tumor growth (i.e., proliferation and survival) as well as metastasis (eg, invasion and clonogenicity). [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BAF3 MU\DfZRwfG:6aXOgRZN{[Xl? MXK0PEBp MnHVSG1UVw>? MmPWR5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmFHOyClZXzsd{BmgHC{ZYPzbY5oKEGOSzDGNVE4PExibYX0ZY51KGOxZYjwdoV{e2mwZzDFUWw1KHerdHigTWM2OCCxZjCwMlYzKM7:TR?= MkXkNlE2PzJ3OEm=
BAF3 MlTkR5l1d3SxeHnjJGF{e2G7 M1X2[lQ5KGh? MX;EUXNQ MYnDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRWY{KGOnbHzzJIV5eHKnc4PpcochSUyNIFyxNVk3VSCvdYThcpQh[2:neIDy[ZN{cW6pIFXNUFQhf2m2aDDJR|UxKG:oIEKuNkDPxE1? M2mxV|IyPTd{NUi5
BAF3 MoHBR5l1d3SxeHnjJGF{e2G7 MoTiOFghcA>? MnfXSG1UVw>? NWnSdHNoS3m2b4TvfIlkcXS7IHHnZYlve3RibX;1d4UhSkGIMzDj[YxteyCneIDy[ZN{cW6pIFXNUFQuSUyNIIfpeIghUUN3MDDv[kAxNjJ6IN88US=> NGewdW0zOTV5MkW4PS=>
Kelly NWD5UlhZS3m2b4TvfIlkKEG|c3H5 NFPle2pFVVOR Mn22R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gT4VtdHliY3XscJMh\XiycnXzd4lv\yCDTFugSlEyPzSOIH31eIFvfCC5aYToJGlEPTBib3[gNE41OiEQvF2= M4DhZ|IyPTd{NUi5
SH-SY5Y M3HsdGN6fG:2b4jpZ{BCe3OjeR?= NXHX[2RTTE2VTx?= M4Pm[2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHNJNVO\NWmgZ4VtdHNiZYjwdoV{e2mwZzDBUGshTjFzN{TMJI12fGGwdDD3bZRpKEmFNUCgc4YhOC53MzFOwG0> M{nsflIyPTd{NUi5
SMS-KCN MUHDfZRwfG:6aXOgRZN{[Xl? M4W3V2ROW09? NXPab2dvS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hW02VLVvDUkBk\WyuczDlfJBz\XO|aX7nJGFNUyCUMUK3OXEhdXW2YX70JJdqfGhiSVO1NEBw\iByLkmxJO69VQ>? NHSybYszOTV5MkW4PS=>
BAF3 MYPDfZRwfG:6aXOgRZN{[Xl? M1rENFQ5KGh? M3rtWmROW09? Mn3CR5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmFHOyClZXzsd{BmgHC{ZYPzbY5oKFSnbD3BUGshf2m2aDDJR|UxKG:oIECuNVkh|ryP M3XnOVIyPTd{NUi5
3T3 NFnnOGZHfW6ldHnvckBCe3OjeR?= M4H4eFEhcA>? NFzndINFVVOR NEnUNYtKdmirYnn0bY9vKG:oIGLPUkBie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6wPEDPxE1? M{fhSlIyQDF{NEG0
3T3-E NHf2dGdHfW6ldHnvckBCe3OjeR?= NIrYWYYyKGh? NGrNWplFVVOR M130bGlvcGmkaYTpc44hd2ZiVFnFNkBie3Onc4Pl[EBoem:5dHig[oFkfG:{LXnu[JVk\WRiYYX0c5Bpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOC52NEig{txO Mlz0NlE5OTJ2MUS=
A549 NXL3e5dYU2mwYYPlJGF{e2G7 MXOxJIg> MlfkSG1UVw>? NHS5cJlKdmirYnn0bY9vKG:oIHj1cYFvKHKnY3;tZolv[W62IHOtUWVVKGurbnHz[UBmgHC{ZYPz[YQh[XO|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBJT0ZvaX7keYNm\CCjdYTvdIhwe3Cqb4L5cIF1cW:wIIfpeIghUUN3MDDv[kAxNjByODFOwG0> NF\HbHYzOThzMkSxOC=>
BAF3-BCL Mn3ZSpVv[3Srb36gRZN{[Xl? NITGWYsyKGh? NHqyT4NFVVOR NWnsNJU3UW6qaXLpeIlwdiCxZjDBRmwh[XO|ZYPz[YQh[XNiZ4Lve5RpKG[jY4Tvdk1qdmS3Y3XkJIF2fG:yaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIEGuNVU6KM7:TR?= MWmyNVgyOjRzNB?=
HEK293 MX3GeY5kfGmxbjDBd5NigQ>? Mom1NUBp M4SybWROW09? MoX6TY5pcWKrdHnvckBw\iCDWFygZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwMkm0JO69VQ>? NY\DU5h7OjF6MUK0NVQ>
HEK293 MlvBSpVv[3Srb36gRZN{[Xl? NXvEZ5NqOSCq MnqxSG1UVw>? M1rGVGlvcGmkaYTpc44hd2ZiSWKgZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDJwOEi3JO69VQ>? MlXxNlE5OTJ2MUS=
Jurkat MVTGeY5kfGmxbjDBd5NigQ>? MnLSNUBp NFnpZZpFVVOR NFiweGtKdmirYnn0bY9vKG:oIFzDT{Bie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMj63OFEh|ryP MYCyNVgyOjRzNB?=
KARPAS299 MYTLbY5ie2ViQYPzZZk> NGXDPW4yKGh? MYTEUXNQ NGG2clBKdmirYnn0bY9vKG:oIFHMT{Bie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6wNkDPxE1? MVSyNVgyOjRzNB?=
PAE MYrGeY5kfGmxbjDBd5NigQ>? NGPoVVYyKGh? MlHGSG1UVw>? MmPQTY5pcWKrdHnvckBw\iCWUlvCJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iByLkO5PUDPxE1? NVHH[21{OjF6MUK0NVQ>
BAF3 NVnDRpc5TnWwY4Tpc44hSXO|YYm= Ml7vNk0{KGR? NV7uNFJ[TE2VTx?= M1fJe2lvcGmkaYTpc44hd2ZiVFXMMYZ2e2WmIHnud5VtcW5icnXj[ZB1d3JiZYjwdoV{e2WmIIfpeIghUUN3MDDv[kAyNjZ2MzFOwG0> Ml2wNlM4PDJ{NUK=
KARPAS299 MYrDfZRwfG:6aXOgRZN{[Xl? MkfLNk0{KGR? M2HFV2ROW09? NEDteXlKSzVyPUCuNFY1OiEQvF2= NXjKPW9VOjN5NEKyOVI>
EBC1 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3XwSlczKGh? MWrEUXNQ MljjTWM2OD1yLkCyN{DPxE1? MYKyN|k6OzN{OB?=
HCT116 MmPMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH7peW84OiCq NV;xdJBYTE2VTx?= MVHJR|UxRTF2LkiyJO69VQ>? NGjXXWIzOzl7M{OyPC=>
MCF7 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4nsOlczKGh? Ml60SG1UVw>? M4P4e2lEPTB;OT61PEDPxE1? M3LBVVI{QTl|M{K4
MDA-MB-231 NILkV2pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2H6VVczKGh? NILIbnlFVVOR NHL4O5NKSzVyPUGwMlgh|ryP MlLTNlM6QTN|Mki=
MKN45 NXLNW4ZMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3;PV|czKGh? NX;1XIRxTE2VTx?= NInoWoNKSzVyPUCuNFE{KM7:TR?= MV:yN|k6OzN{OB?=
NCI-H441 NGr4SmlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYjNOnh2PzJiaB?= MmOzSG1UVw>? NHzJfVdKSzVyPUG3MlI2KM7:TR?= NF;Bb28zOzl7M{OyPC=>
NCI-H661 M2DETWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoWyO|IhcA>? Moq1SG1UVw>? NV7sbnY3UUN3ME2xNU41PyEQvF2= MnX4NlM6QTN|Mki=
SK-MEL-28 MornS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFPV[XE4OiCq NETFcFFFVVOR M4LidmlEPTB;MUCuPVch|ryP NVTV[mNZOjN7OUOzNlg>
SKOV3 M3XWUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn7tO|IhcA>? NXjsWFBDTE2VTx?= MmjoTWM2OD1zMj64OUDPxE1? MnjwNlM6QTN|Mki=
SNU5 MoHYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mne2O|IhcA>? NXPv[5E6TE2VTx?= MYnJR|UxRTBwMEG2JO69VQ>? M4jFTFI{QTl|M{K4
NCI-H2228 M2jzd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3PM[lczKGh? MorqSG1UVw>? MV3Jcohq[mm2aX;uJI9nKEGOSz3meZNqd25iZILpeoVvKGOnbHygdJJwdGmoZYLheIlwdiC5aYToJGlEPTBib3[gNE4yOThizszN MVKyOFQ{OjlyOR?=
NCI-H3122 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFPvNZE4OiCq MVTEUXNQ MmLXTY5pcWKrdHnvckBw\iCDTFut[pV{cW:wIHTybZZmdiClZXzsJJBzd2yrZnXyZZRqd25id3n0bEBKSzVyIH;mJFAvOTB6IN88US=> NGP5UVkzPDR|MkmwPS=>
NCI-H3122 Mm\5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX:3NkBp M2eyVmROW09? M2PvVmlvcGmkaYTpc44hd2ZiQVzLMYZ2e2mxbjDkdol3\W5iY3XscEBxem:uaX\ldoF1cW:wIHnuJIh2dWGwIF7DTU1JOzF{MjDj[YxteyCqYYLic5JqdmdiQVzLJGcyOjZ7QTDteZRidnRid3n0bEBKSzVyIH;mJFAvPjJ|IN88US=> M2Xl[|I1PDN{OUC5
NCI-H3122 NUPmWXhxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXi3NkBp Ml2zSG1UVw>? MYPJcohq[mm2aX;uJI9nKEGOSz3meZNqd25iZILpeoVvKGOnbHygdJJwdGmoZYLheIlwdiCrbjDoeY1idiCQQ1mtTFMyOjJiY3XscJMhcGG{Yn;ybY5oKEGOSzDMNVE6Pk1ibYX0ZY51KHerdHigTWM2OCCxZjCwMlg{QCEQvF2= MUiyOFQ{OjlyOR?=
NIH-3T3 M{fXdGtqdmG|ZTDBd5NigQ>? MWexJIg> NXfCfGhoTE2VTx?= MnS5TY5pcWKrdHnvckBw\iCqdX3hckB4cWymIIT5dIUhTU2OND3meZNm\CCDTFug[ZhxemW|c3XkJIF{e2W|c3XkJIF{KHCqb4PwbI9zgWyjdHXkJGFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMD6wPEDPxE1? NHXacGUzPDR|MkmwPS=>
NIH-3T3 NULpXFIxU2mwYYPlJGF{e2G7 NXjqbGc2OSCq NVrDXlVLTE2VTx?= M{DaOWlvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugS|EzPjmDIH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDBwNkC1JO69VQ>? NVzVcmkxOjR2M{K5NFk>
NIH-3T3 MV7LbY5ie2ViQYPzZZk> NHL1RVAyKGh? M1ztfWROW09? NYDVdI1PUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BUOTJyNmmgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMD62NlYh|ryP M1nocFI1PDN{OUC5
NIH-3T3 Mn7HT4lv[XOnIFHzd4F6 MkDZNUBp MVrEUXNQ M3LmeGlvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugUFEyQT[PIH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDBwOESzJO69VQ>? NEO0S5EzPDR|MkmwPS=>
NIH-3T3 M4r2UWtqdmG|ZTDBd5NigQ>? NYjJc|g1OSCq NEfwVpNFVVOR NVLHbpNSUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BNOTF3MmKgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMT6wNlYh|ryP MUSyOFQ{OjlyOR?=
BAF3 MlTHSpVv[3Srb36gRZN{[Xl? NGO5W4k4OiCq NInIeGpFVVOR M1T2[WlvcGmkaYTpc44hd2ZiTmDNM2FNUyC2cnHud4Zm[3SnZDDhd5Nme3OnZDDhd{Bk\WyuIHfyc5d1cCCrbnjpZol1cW:wIIfpeIghUUN3MDDv[kAxNjB3MTFOwG0> M{K3d|I1PDZ6NkOy
BAF3 M{LXbGN6fG:2b4jpZ{BCe3OjeR?= Mo\pO|IhcA>? M3nq[GROW09? NXTrd25kUUN3ME2wMlk5KM7:TR?= MnPPNlQ1Pjh4M{K=
NIH-3T3 NV63UId{U2mwYYPlJGF{e2G7 NWm0Vld[OSCq NVu1RodJUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BHOTF5NFygcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMD6xOlUh|ryP NH\vSIYzPDhzOUGxOi=>
NIH-3T3 Mn\VT4lv[XOnIFHzd4F6 M2LYNlEhcA>? MYfJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIFOxNVU3YSCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAxNjR5ODFOwG0> M1vSNVI1QDF7MUG2
NIH-3T3 MUTLbY5ie2ViQYPzZZk> MYixJIg> MUTJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIFexNlAzWiCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAyNjF2ODFOwG0> M1KxZlI1QDF7MUG2
NIH-3T3 MkjmT4lv[XOnIFHzd4F6 M1XUSFEhcA>? NXL4R4l[UW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{AyOTVzVHnud{BufXSjboSg[ZhxemW|c3XkJIF{e2W|c3XkJIF{KHCqb4PwbI8uSUyNIHzleoVtKHerdHigTWM2OCCxZjCzMlA{QSEQvF2= M4jUT|I1QDF7MUG2
KARPAS299 M{PuWWtqdmG|ZTDBd5NigQ>? NHrHToo6OCCvaX6= NV7zZWc4TE2VTx?= M{H5OWlvcGmkaYTpc44hd2ZiTmDNMYZ2e2WmIFHMT{BxcG:|cHjvdplt[XSrb36g[ZhxemW|c3XkJJdqfGhiSVO1NEBw\iByLkGxJO69VQ>? Ml[xNlQ6ODB5NUC=
MKN 45 M3nSO2tqdmG|ZTDBd5NigQ>? M1O5clEhcA>? MV;EUXNQ M1jzNmlvcGmkaYTpc44hd2ZiYz3N[ZQheGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iByLkCyJO69VQ>? NIG5XGYzPDlyMEe1NC=>
A549 M3S0dWN6fG:2b4jpZ{BCe3OjeR?= M1nQc|Q5KGh? M123PGROW09? NYrRbpdtUUN3MDDv[kA1NjB6NDFOwG0> NX[xe497OjR7MEC4N|A>
NCI-H1975 NUP6cJRIS3m2b4TvfIlkKEG|c3H5 Mly1OFghcA>? NVHkc2Y1TE2VTx?= NVn0c4U5UUN3MDDv[kA4NjV3MTFOwG0> NYjRfmw2OjR7MEC4N|A>
NCI-H1993 NGn5XlBEgXSxdH;4bYMhSXO|YYm= MXu0PEBp M{O0N2ROW09? MX7JR|UxKG:oIECuNFYyKM7:TR?= MYmyOFkxODh|MB?=
NCI-H1993 M1H6fWFxd3Sxc3nzJGF{e2G7 NX76T4RiOSEQvF2= NVzOc4wxOjRiaB?= MUXEUXNQ NHP2[otld2W|IH7veEBqdmS3Y3WgZZBweHSxc3nz M3TMSVI1QTByOEOw
NIH-3T3 MWfDfZRwfG:6aXOgRZN{[Xl? MlXtOFghcA>? NUjFb4gzTE2VTx?= MljRTWM2OCCxZjCwMlM3PCEQvF2= NX\YU2RjOjR7MEC4N|A>
EBC1 MlLHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnLjO|IhcA>? Ml\SSG1UVw>? MoXyTWM2OCCxZjCwMlAxPjlizszN NFfU[XUzPDlyMEizNS=>
KARPAS299 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHO0Sng4OiCq MnzmSG1UVw>? MnfVTWM2OCCxZjCwMlIh|ryP MXqyOFkxODh|MR?=
NB1 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXPJR|UxRTlzLkm4JI5O NXvadFVRW0GQR1XS
NCI-SNU-5 MkmyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2LkNGlEPTB;MUC1Mlc2KG6P M1vLSnNCVkeHUh?=
SR M3\0R2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGL4RlNKSzVyPUGyOk4{OSCwTR?= MVnTRW5ITVJ?
SF539 NWPVVVdrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXXmdo9JUUN3ME2yNFQvOjRibl2= MmXLV2FPT0WU
SU-DHL-1 M33OVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX3NdlZ2UUN3ME2zN|YvQDJibl2= M1XwVXNCVkeHUh?=
SCC-3 NH7pbmJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUnJR|UxRTN3Nj63OkBvVQ>? MUTTRW5ITVJ?
DEL NFTxWZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUXtUoRvUUN3ME2zOlkvQSCwTR?= MkHmV2FPT0WU
CTV-1 NHnEOIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYHPS4JrUUN3ME21PVYvPDhibl2= M{PvOXNCVkeHUh?=
EM-2 MlL6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{fhdmlEPTB;NkCxMlM1KG6P NXLFO3RmW0GQR1XS
MHH-CALL-2 Mk\sS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1y4NGlEPTB;NkiyMlU4KG6P NGfSNGJUSU6JRWK=
KM12 M{L4V2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFvyWW5KSzVyPUewOk46KG6P NVXnS4xlW0GQR1XS
KINGS-1 NUfQdZhJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnO0TWM2OD15NEmuO|Uhdk1? MWfTRW5ITVJ?
MEG-01 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXzJR|UxRTh3Nz62OkBvVQ>? MmDVV2FPT0WU
BV-173 NF7hR5NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1PxfWlEPTB;MT6wOVk6PyEQvF2= MmPDV2FPT0WU
LAMA-84 MmXXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{nlZ2lEPTB;MT6zPFI5OiEQvF2= Mn:2V2FPT0WU
KARPAS-299 MoXFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NICzOnVKSzVyPUGuOFA5PjFizszN Ml\LV2FPT0WU
K-562 MkDyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1O3ZWlEPTB;MT63NlI3QSEQvF2= Mn\xV2FPT0WU
SK-LMS-1 M2TVZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M33rS2lEPTB;MT63Olg3PyEQvF2= Mk\WV2FPT0WU
MOLT-16 M3fKVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGjRdYNKSzVyPUGuPVU2PzVizszN M3jYeXNCVkeHUh?=
CMK Mnu4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYDJR|UxRTFwOU[xOVkh|ryP M1fNfHNCVkeHUh?=
ST486 MmLMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWTTU|lJUUN3ME2yMlQ{ODd|IN88US=> MXXTRW5ITVJ?
CI-1 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmnGTWM2OD1{LkS5OlU6KM7:TR?= Ml\nV2FPT0WU
KP-N-RT-BM-1 NFTqenNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnfwTWM2OD1{LkewNVIzKM7:TR?= NI\OPWxUSU6JRWK=
ALL-PO NFPUS5BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWfJR|UxRTNwMUiyNFch|ryP NYPa[VdWW0GQR1XS
KS-1 NWXKNHZRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX7MZoZIUUN3ME2zMlIyOjJ3IN88US=> MXLTRW5ITVJ?
Becker MmjlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2PaOWlEPTB;ND6yN|k{KM7:TR?= M1nYOHNCVkeHUh?=
GDM-1 M172UGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2LmfmlEPTB;ND6yOFYyPyEQvF2= M4LIRnNCVkeHUh?=
BC-1 NFXDcFlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4jaUmlEPTB;ND60PVI4PyEQvF2= NEG2PFdUSU6JRWK=
NB14 M1;Eb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MorvTWM2OD12LkizOVI1KM7:TR?= MkjMV2FPT0WU
NOS-1 M4G0TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIeyb|NKSzVyPUWuN|M5PzRizszN Mn:zV2FPT0WU
MZ1-PC NEPQUWhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVfTc|N3UUN3ME21MlgzOTVzIN88US=> MXfTRW5ITVJ?
A498 MoW0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUKxPGV6UUN3ME22MlA5PDd|IN88US=> MmDwV2FPT0WU
EW-16 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3PvS2lEPTB;Nj6zO|c4OyEQvF2= NX7jPVFjW0GQR1XS
NALM-6 NXr2fWlrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUDn[ZhjUUN3ME22MlY5Ozh5IN88US=> M33n[XNCVkeHUh?=
EB-3 MljSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVXJR|UxRTdwMEeyN|Mh|ryP M{LWN3NCVkeHUh?=
697 MlfyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4TIeGlEPTB;OT6yOFMzQSEQvF2= NWG1TVNCW0GQR1XS
Ramos-2G6-4C10 M{DINWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFnOPJFKSzVyPUmuOVk5PDJizszN MnvSV2FPT0WU
KNS-81-FD MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4LiPWlEPTB;OT62PVY2OyEQvF2= NFfKSnZUSU6JRWK=
HUTU-80 NG\FSplIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV\JcWJwUUN3ME25Mlc1PjR{IN88US=> NFiweXhUSU6JRWK=
LS-411N MnrzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX;JR|UxRTFyLkC1Olch|ryP M2HVW3NCVkeHUh?=
RPMI-8402 NUKzTHA2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3[3cGlEPTB;MUCuNVE3KM7:TR?= MkCxV2FPT0WU
KU812 NVPwNYZzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1flV2lEPTB;MUCuNlk6OSEQvF2= MWXTRW5ITVJ?
EW-1 NVvFNGpFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mne3TWM2OD1zMD60OFI2KM7:TR?= M{LZRXNCVkeHUh?=
HC-1 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUfNOXlnUUN3ME2xNE41QDR2IN88US=> MmXkV2FPT0WU
NB69 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWi2O|VtUUN3ME2xNE42ODR|IN88US=> NV;6U2ozW0GQR1XS
MFH-ino NYH1O|hsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4P6PWlEPTB;MUCuPFMxOyEQvF2= NXzzbpBRW0GQR1XS
CCRF-CEM M{G3cGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUXJR|UxRTFzLkW5O{DPxE1? MWDTRW5ITVJ?
SK-N-DZ MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUTJR|UxRTF{LkC0N|Yh|ryP NFL2RVdUSU6JRWK=
NCI-H720 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXP1TWxEUUN3ME2xNk4yPzB3IN88US=> NI\LZmdUSU6JRWK=
HCC1187 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlHNTWM2OD1zMj6yNFQyKM7:TR?= NWHJZZJwW0GQR1XS
IST-SL2 NIrpb21Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnPtTWM2OD1zMj60PFczKM7:TR?= NV[4fJNJW0GQR1XS
KE-37 NX75SGJlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXLTTGpNUUN3ME2xNk44QTZ4IN88US=> NX3BSI9sW0GQR1XS
HCC1599 NVryOIZuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVPHOJRlUUN3ME2xNk46ODZ7IN88US=> NH60c29USU6JRWK=
A4-Fuk MmjYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYG3TllMUUN3ME2xNk46PTh4IN88US=> NELud2NUSU6JRWK=
NKM-1 M3GxcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkW4TWM2OD1zMz6yPVI2KM7:TR?= MUHTRW5ITVJ?
BE-13 NHmzTlVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{nJWmlEPTB;MUOuO|k5QSEQvF2= NEjXTpBUSU6JRWK=
MV-4-11 MmHHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1z4S2lEPTB;MUSuNFMzPCEQvF2= MnjLV2FPT0WU
OPM-2 M3\DfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1zNbGlEPTB;MUSuOFA5PSEQvF2= NUHrWnlmW0GQR1XS
KARPAS-422 MmHRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1;SVWlEPTB;MUSuOVEzPiEQvF2= NFLldI1USU6JRWK=
RPMI-8226 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHHvU4JKSzVyPUG0Mlg6OTVizszN MkLIV2FPT0WU
KARPAS-45 NXf2SpVjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVvJR|UxRTF3Lke3NVYh|ryP Mk[4V2FPT0WU
SK-PN-DW NYLVSHM3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVTJR|UxRTF3Lki2N|Eh|ryP NXW3fYNKW0GQR1XS
LC-2 MmO1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYnJR|UxRTF4LkG1NFYh|ryP MmPXV2FPT0WU
NCI-H1648 NX;5OIc1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXvyZZBMUUN3ME2xOk4zPTRizszN Ml3VV2FPT0WU
RL95-2 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIjFdnRKSzVyPUG2MlM6PzhizszN NEezU5JUSU6JRWK=
KNS-42 MknPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXz4NFl{UUN3ME2xOk44Ojd2IN88US=> NF7HVpRUSU6JRWK=
RPMI-6666 Ml;CS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXXJR|UxRTF4LkmyNVEh|ryP MYjTRW5ITVJ?
SIG-M5 NV\RXHdvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mkj6TWM2OD1zNz6xPVA{KM7:TR?= NHLXSGRUSU6JRWK=
VA-ES-BJ M4\IdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn3lTWM2OD1zNz63OFUyKM7:TR?= NV3OOmJEW0GQR1XS
MONO-MAC-6 NYfQXGlDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXHOS2hLUUN3ME2xO{46OzF{IN88US=> M3XMcHNCVkeHUh?=
LAN-6 NFPCbFJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHHDdGxKSzVyPUG4Mlc2PTdizszN M1LIN3NCVkeHUh?=
A388 NXTaXmRnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX;JR|UxRTF7LkOwOVkh|ryP MmPrV2FPT0WU
SK-NEP-1 NImz[pdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmjXTWM2OD1{MD6yNVMzKM7:TR?= M{nFZ3NCVkeHUh?=
TE-10 MlvLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEHNOGhKSzVyPUKwMlUzOjFizszN MmPhV2FPT0WU
HL-60 NXHHc5JLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWG0UG5SUUN3ME2yNE46ODl7IN88US=> NFPhOmNUSU6JRWK=
MC116 M3nvfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWDob3ZVUUN3ME2yNU44OjJzIN88US=> NVyyTlVFW0GQR1XS
SW962 MoPwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVzDfYJPUUN3ME2yNU44QTF3IN88US=> MUnTRW5ITVJ?
NOMO-1 M4DuN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWPZNWxqUUN3ME2yNk43PTZ2IN88US=> MoTzV2FPT0WU
CTB-1 MnnNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGDYS3JKSzVyPUKyMlg3PzFizszN NEDDeVdUSU6JRWK=
MRK-nu-1 NX7EdY52T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUTUXJBPUUN3ME2yNk46ODd2IN88US=> NUn2R|k6W0GQR1XS
GR-ST MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlLNTWM2OD1{Mz63OkDPxE1? MnHpV2FPT0WU
HH NWH0fFBST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmW2TWM2OD1{ND6wNFMh|ryP MYTTRW5ITVJ?
NCI-H1963 M3vGcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXLJR|UxRTJ2LkC3PFIh|ryP MYLTRW5ITVJ?
QIMR-WIL NEDnUoNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVLxOIg5UUN3ME2yOE45Pzd{IN88US=> NFHFNVBUSU6JRWK=
CGTH-W-1 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX\JeYg3UUN3ME2yOU4xPzJ|IN88US=> NEHBUWdUSU6JRWK=
LP-1 NXu2XpJqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoXCTWM2OD1{NT62OVUyKM7:TR?= MnL3V2FPT0WU
NCI-H748 MonYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3[4O2lEPTB;Mk[uOVE{PyEQvF2= NHnXTpVUSU6JRWK=
PF-382 MnzFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEHSdXNKSzVyPUK3MlIzOjNizszN M3HyZXNCVkeHUh?=
ATN-1 Mn70S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4\weGlEPTB;MkeuN|c{OiEQvF2= Mk\TV2FPT0WU
L-540 NXLTOo9{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH;4OolKSzVyPUK3MlY1PTlizszN NXT0PZY5W0GQR1XS
LXF-289 MlfDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVGxT|UyUUN3ME2yO{44PTF7IN88US=> NFnBXW9USU6JRWK=
LS-513 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFjaVHhKSzVyPUK4MlE5ODdizszN Mn\SV2FPT0WU
NCI-H1581 NYfr[HhzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mke0TWM2OD1|MD6zPVc3KM7:TR?= Mn24V2FPT0WU
ES6 M1P5d2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGj1ZnZKSzVyPUOwMlY5QTlizszN M4\6U3NCVkeHUh?=
SW982 NFXw[Y9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVfJR|UxRTNyLki1OlYh|ryP NVXJe3R2W0GQR1XS
DOHH-2 MnTuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1LvN2lEPTB;M{GuOVg6OyEQvF2= NV3VTYh6W0GQR1XS
DB MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH\Y[ZBKSzVyPUOzMlk1OzFizszN MmjOV2FPT0WU
MPP-89 M16xb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUDJR|UxRTN2LkG3OVYh|ryP MX7TRW5ITVJ?
LB831-BLC NVzNVmg5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2LNTmlEPTB;M{SuOVE5PCEQvF2= NEmyfoNUSU6JRWK=
NB5 M{LUXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUPJR|UxRTN2Lki1N|Uh|ryP Mn7yV2FPT0WU
GB-1 NY\MPGljT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGLiSJpKSzVyPUO1MlA1PjlizszN MmPwV2FPT0WU
TE-15 MlvCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFHwUFhKSzVyPUO1MlIzOzhizszN MYDTRW5ITVJ?
LC4-1 Ml\sS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH\5NG5KSzVyPUO1MlM5PDdizszN M2TzWXNCVkeHUh?=
NCI-H747 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn\XTWM2OD1|Nj6xN|Y6KM7:TR?= MoTmV2FPT0WU
NTERA-S-cl-D1 MoLjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV;HRXBrUUN3ME2zPE44OzR5IN88US=> MWDTRW5ITVJ?
SK-MM-2 NXnxSGJUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYrkWHlbUUN3ME20NE4yOTR4IN88US=> NWfRToQyW0GQR1XS
TGW M4XZd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHfscFJKSzVyPUSxMlA2PjNizszN MWHTRW5ITVJ?
ONS-76 NGHhZmlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGLXcHhKSzVyPUSyMlQ5QDNizszN NFL3c21USU6JRWK=
CPC-N MmfPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXfVd4hKUUN3ME20Nk46QTdzIN88US=> MX7TRW5ITVJ?
ES4 NWfTW3RET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHnaNo1KSzVyPUS0MlQyPTNizszN M2LLbnNCVkeHUh?=
Daudi NHnDblJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFPtcGpKSzVyPUS1MlA5OjdizszN MnOyV2FPT0WU
MOLT-4 MoHkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYHJR|UxRTR3LkC4OVMh|ryP NH3nWpBUSU6JRWK=
HT-144 MlHNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWLJTlluUUN3ME20Ok44OjZizszN NF3sZZlUSU6JRWK=
SW872 NHO0RopIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYnTT4tSUUN3ME20PE4yQTN|IN88US=> MnvsV2FPT0WU
D-283MED NX3uc5RZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml[2TWM2OD12OD6zOVQzKM7:TR?= M3zvUXNCVkeHUh?=
NCI-H2126 M4nqU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUjYUmh6UUN3ME20PE45PDd4IN88US=> NXTHb|RXW0GQR1XS
NCI-SNU-16 NX\hc4NsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHH0[FRKSzVyPUS5MlIyPDNizszN NFTwWXZUSU6JRWK=
CESS NHS3eoFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWrJR|UxRTR7LkWwPFgh|ryP MUXTRW5ITVJ?
A101D Mki0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmLETWM2OD12OT65O|M3KM7:TR?= MkHPV2FPT0WU

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
pALK / pAKT / pERK / pS6; 

PubMed: 24675041     


H3122 cells were treated with the indicated concentrations of crizotinib or ceritinib for 6 hours. Lysates were probed with antibodies directed against the specified proteins.

pROS1 / ROS1; 

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.

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.

PARP / cleaved caspase-3 / Bax / Bcl-2; 

PubMed: 25193856     


The expression of PARP, cleaved caspase-3, Bax, and Bcl-2 were measured by western blotting after PANC-1 cells were treated with various concentrations of Crizotinib (0-10 μM) for 72 hr.

p-c-Met / c-Met; 

PubMed: 25193856     


Cancer cells with c-MET alterations were exposed to Crizotinib (10 μM) in the indicated times (SNU-5, MKN-45, and SNU-638: gastric cancer cells of c-MET amplification).

p-mTOR; 

PubMed: 26384345     


Immunoblotting for phospho- or total MET, STAT3, AKT, MTOR and ERK in SPC-A1 cells treated with crizotinib for 48 h.

24675041 25351743 25193856 26384345
Immunofluorescence
LC3 / lysosome; 

PubMed: 26384345     


Cells were treated with DMSO or 4 μM crizotinib for 72 h before they were labeled with a fluorescent marker and imaged by fluorescence microscopy. Green: FITC-labeled LC3; Red: lyso-tracker-labeled lysosome; Blue: DAPI-labeled nucleus. 

SRC / Met; 

PubMed: 26517812     


Cellular localization of SRC and Met following treatment for 48 h with dasatinib, crizotinib or combination in (A) LN-18 and (B) U373 cells. Scale bar denotes 10 μm. Nuclei were visualized by DAPI while SRC and Met were labeled with a fluorescein and Texas-red conjugated secondary antibodies, respectively.

α-tubulin; 

PubMed: 26517812     


LN-18 cells were treated with dasatinib 0.2 μM, crizotinib 4 μM or their combination for 48 h. Mitotic spindle were visualized using α-tubulin antibody conjugated to a fluorescein-labeled secondary antibody. Nuclei were stained by DAPI. The scale bar denotes 10 μm.

cytochrome c; 

PubMed: 25193856     


PANC-1 pancreatic cancer cells were treated with Crizotinib (1 and 10 μM) for 6 hr and stained with anti-cytochrome c antibody, Mitotracker and DAPI. The immunostained cells were analyzed under an Olympus confocal laser scanning microscope with 400x magnification. Cytochrome c (green), mitotracker: red

p-ALK; 

PubMed: 25193856     


PANC-1 cells were also treated with various concentrations (0-10 μM) of Crizotinib and stained with p-ALK antibody and DAPI. The immunostained cells were analyzed under an Olympus confocal laser scanning microscope with 400x magnification.

26384345 26517812 25193856
In vivo

In the GTL-16 model, PF-2341066 reveals the ability to cause marked regression of large established tumors (>600 mm3) in both the 50 mg/kg/day and 75 mg/kg/day treatment cohorts, with a 60% decrease in mean tumor volume over the 43-day administration schedule. In an another study, PF-2341066 displays the ability to completely inhibits GTL-16 tumor growth for >3 months, with only 1 of 12 mice exhibiting a significant increase in tumor growth over the 3-month treatment schedule at 50 mg/kg/day. In the NCI-H441 NSCLC model, a 43% decrease in mean tumor volume is observed at 50 mg/kg/day during the 38-day PF-2341066 administration cycle. In the Caki-1 RCC model, a 53% decrease in mean tumor volume is observed to be associated with decreased volume of each tumor by at least 30% at 50 mg/kg/day during the 33-day PF-2341066 administration cycle. PF-2341066 also reveals near-complete prevention of the growth of established tumors at 50 mg/kg/day in the U87MG glioblastoma or PC-3 prostate carcinoma xenograft models, with 97% or 84% inhibition on the final study day, respectively. In contrast, PF-2341066 p.o. given at 50 mg/kg/day does not significantly inhibit tumor growth in the MDA-MB-231 breast carcinoma model, or the DLD-1 colon carcinoma model. A significant dose-dependent reduction of CD31–positive endothelial cells is observed at 12.5 mg/kg/day, 25 mg/kg/day, and 50 mg/kg/day in GTL-16 tumors, indicating that inhibition of MVD shows a dose-dependent correlation to antitumor efficacy. PF-2341066 displays a significant dose-dependent reduction of human VEGFA and IL-8 plasma levels in both the GTL-16 and U87MG models. Marked inhibition of phosphorylated c-Met, Akt, Erk, PLCλ1, and STAT5 levels is observed in GTL-16 tumors following p.o. administration of PF-2341066.[1] P.o. administration of PF-2341066 to severe combined immunodeficient-Beige mice bearing Karpas299 ALCL tumor xenografts leads to dose-dependent antitumor efficacy with complete regression of all tumors at the 100 mg/kg/d dose within 15 days of initial compound administration. In addition, inhibition of key NPM-ALK signaling mediators, including phospholipase C-gamma, signal transducers and activators of transcription 3, extracellular signal-regulated kinases, and Akt by PF-2341066 are observed at concentrations or dose levels, which correlated with inhibition of NPM-ALK phosphorylation and function.[2] PF-2341066 prevents osteosarcoma behavior associated with primary tumor growth (eg, proliferation and survival) as well as metastasis (eg, invasion and clonogenicity). In nude mice treated with PF-2341066 via oral gavage, the growth and associated osteolysis and extracortical bone matrix formation of osteosarcoma xenografts are prevented by PF-2341066.[3] Treatment of c-MET-amplified GTL-16 xenografts with 50 mg/kg PF-2341066 elicits tumor regression that is associated with a slow reduction in 18F-FDG uptake and decreases expression of the glucose transporter 1, GLUT-1.[4]

Protocol

Kinase Assay:

[1]

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Cellular kinase phosphorylation ELISA assays:

Cells are seeded in 96-well plates in media supplemented with 10% fetal bovine serum (FBS) and transferred to serum-free media [with 0.04% bovine serum albumin (BSA)] after 24 h. In experiments investigating ligand-dependent RTK phosphorylation, corresponding growth factors are added for up to 20 min. After incubation of cells with PF-2341066 for 1 h and/or appropriate ligands for the designated times, cells are washed once with HBSS supplemented with 1 mM Na3VO4, and protein lysates are generated from cells. Subsequently, phosphorylation of selected protein kinases is assessed by a sandwich ELISA method using specific capture antibodies used to coat 96-well plates and a detection antibody specific for phosphorylated tyrosine residues. Antibody-coated plates are (a) incubated in the presence of protein lysates at 4°C overnight; (b) washed seven times in 1% Tween 20 in PBS; (c) incubated in a horseradish peroxidase–conjugated anti–total-phosphotyrosine (PY-20) antibody (1:500) for 30 min; (d) washed seven times again; (e) incubated in 3,3′,5,5′-tetramethyl benzidine peroxidase substrate to initiate a colorimetric reaction that is stopped by adding 0.09 N H2SO4; and (f) measured for absorbance in 450 nm using a spectrophotometer.
Cell Research:

[1]

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  • Cell lines: GTL-16 gastric carcinoma cells and T47D breast carcinoma cells
  • Concentrations: 0-256 nM
  • Incubation Time: 1 hour
  • Method:

    Cells including GTL-16 gastric carcinoma cells and T47D breast carcinoma cells are seeded in 96-well plates in media supplemented with 10% fetal bovine serum (FBS) and transferred to serum-free media [with 0.04% bovine serum albumin (BSA)] after 24 hours. In experiments investigating ligand-dependent RTK phosphorylation, corresponding growth factors are added for up to 20 minutes. After incubation of cells with PF-2341066 for 1 hour and/or appropriate ligands for the designated times, cells are washed once with HBSS supplemented with 1 mM Na3VO4, and protein lysates are generated from cells. Subsequently, phosphorylation of selected protein kinases is assessed by a sandwich ELISA method using specific capture antibodies used to coat 96-well plates and a detection antibody specific for phosphorylated tyrosine residues. Antibody-coated plates are (a) incubated in the presence of protein lysates at 4 °C overnight; (b) washed seven times in 1% Tween 20 in PBS; (c) incubated in a horseradish peroxidase–conjugated anti–total-phosphotyrosine (PY-20) antibody (1:500) for 30 min; (d) washed seven times again; (e) incubated in 3,3,5,5-tetramethyl benzidine peroxidase substrate to initiate a colorimetric reaction that is stopped by adding 0.09 N H2SO4; and (f) measured for absorbance in 450 nm using a spectrophotometer.


    (Only for Reference)
Animal Research:

[1]

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  • Animal Models: Female or male nu/nu mice bearing NCI-H441,or DLD-1, or MDA-MB-231
  • Dosages: 12.5 mg/kg/day, 25 mg/kg/day, and 50 mg/kg/day
  • Administration: Administered via p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 9 mg/mL (19.98 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
5% DMSO+30% PEG 300+dd H2O
For best results, use promptly after mixing.
5mg/mL

* 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 450.34
Formula

C21H22Cl2FN5O

CAS No. 877399-52-5
Storage powder
in solvent
Synonyms N/A
Smiles CC(C1=C(C=CC(=C1Cl)F)Cl)OC2=C(N=CC(=C2)C3=CN(N=C3)C4CCNCC4)N

In vivo Formulation Calculator (Clear solution)

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

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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04148066 Recruiting Diagnostic Test: ctDNA blood sample Carcinoma Non-Small-Cell Lung The Netherlands Cancer Institute|Roche Pharma AG July 17 2019 Phase 2
NCT03439215 Recruiting Drug: Lorlatinib Carcinoma Non-Small-Cell Lung Fondazione Ricerca Traslazionale|Clinical Research Technology S.r.l. June 13 2017 Phase 2
NCT02946216 Unknown status Genetic: ctDNA analysis Non-small Cell Lung Cancer Stage III|Non-Small-Cell Lung Cancer Metastatic|Adenocarcinoma of Lung|EGFR Wildtype First People''s Hospital of Hangzhou November 2016 --
NCT02511184 Terminated Drug: Crizotinib|Drug: Pembrolizumab ALK-positive Advanced NSCLC Pfizer|Merck Sharp & Dohme Corp. October 2015 Phase 1
NCT02419287 Unknown status Drug: crizotinib Anaplastic Large Cell Lymphoma ALK-Positive University of Milano Bicocca April 2015 Phase 2
NCT02499614 Unknown status Drug: Crizotinib Carcinoma Non-Small-Cell Lung Fondazione Ricerca Traslazionale December 2014 Phase 2

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.

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Frequently Asked Questions

  • Question 1:

    Could you tell me whether this product represents the pure R-form of crizotinib, or is the the racemic Crizotinib, so a mixture of the S- and the R-form?

  • Answer:

    Our S1068 Crizotinib is R enantiomer(except batch 05 and 06, they are racemate), and S7505 is S enantiomer.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID