Crizotinib (PF-02341066)

For research use only. Not for use in humans.

Licensed by Pfizer Catalog No.S1068

229 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.

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Selleck's Crizotinib (PF-02341066) has been cited by 229 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.
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 NWjJWodPS3m2b4TvfIlkKEG|c3H5 MX[0PEBp NYHHRYN{TE2VTx?= M2P5T2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KG2xdYPlJGJCTjNiY3XscJMh\XiycnXzd4lv\yCDTFugSlEyPzSOIH31eIFvfCClb3X4dJJme3OrbnegSW1NPCC5aYToJGlEPTBib3[gNE43OiEQvF2= M{TGbVIyPTd{NUi5
BAF3 M1LhSmN6fG:2b4jpZ{BCe3OjeR?= M2fUNVQ5KGh? M2LTT2ROW09? NWHaV4VXS3m2b4TvfIlkcXS7IHHnZYlve3RibX;1d4UhSkGIMzDj[YxteyCneIDy[ZN{cW6pIFHMT{BNOTF7Nl2gcZV1[W62IHPv[ZhxemW|c3nu[{BGVUx2IIfpeIghUUN3MDDv[kAzNjJizszN MmDvNlE2PzJ3OEm=
BAF3 MWXDfZRwfG:6aXOgRZN{[Xl? MVu0PEBp M1XPbmROW09? MlfzR5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmFHOyClZXzsd{BmgHC{ZYPzbY5oKEWPTEStRWxMKHerdHigTWM2OCCxZjCwMlI5KM7:TR?= MWCyNVU4OjV6OR?=
Kelly MVnDfZRwfG:6aXOgRZN{[Xl? MY\EUXNQ M1z1WGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGtmdGy7IHPlcIx{KGW6cILld5NqdmdiQVzLJGYyOTd2TDDteZRidnRid3n0bEBKSzVyIH;mJFAvPDJizszN NFy5fI8zOTV5MkW4PS=>
SH-SY5Y MUfDfZRwfG:6aXOgRZN{[Xl? MkHYSG1UVw>? Mn;OR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV2guW1l3WTDj[YxteyCneIDy[ZN{cW6pIFHMT{BHOTF5NFygcZV1[W62IIfpeIghUUN3MDDv[kAxNjV|IN88US=> MWmyNVU4OjV6OR?=
SMS-KCN NXT4cWExS3m2b4TvfIlkKEG|c3H5 MmjpSG1UVw>? NH;0UFZEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBUVVNvS1POJINmdGy|IHX4dJJme3OrbnegRWxMKFJzMke1VUBufXSjboSge4l1cCCLQ{WwJI9nKDBwOUGg{txO M{D3W|IyPTd{NUi5
BAF3 M1nsXGN6fG:2b4jpZ{BCe3OjeR?= Ml3xOFghcA>? MkjySG1UVw>? NXX6VI8xS3m2b4TvfIlkcXS7IHHnZYlve3RibX;1d4UhSkGIMzDj[YxteyCneIDy[ZN{cW6pIGTlcE1CVEtid3n0bEBKSzVyIH;mJFAvOTlizszN NFHMZ4YzOTV5MkW4PS=>
3T3 NXjUZ4V2TnWwY4Tpc44hSXO|YYm= NVi2Z4lKOSCq M2[yZWROW09? NInkb3hKdmirYnn0bY9vKG:oIGLPUkBie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6wPEDPxE1? NVXiSXBTOjF6MUK0NVQ>
3T3-E Mnz0SpVv[3Srb36gRZN{[Xl? MW[xJIg> NFWwc|FFVVOR MYXJcohq[mm2aX;uJI9nKFSLRUKgZZN{\XO|ZXSg[5Jwf3SqIH\hZ5Rwei2rbnT1Z4VlKGG3dH;wbI9{eGixconsZZRqd25id3n0bEBKSzVyIH;mJFAvPDR6IN88US=> NIO1d5MzOThzMkSxOC=>
A549 M1v0W2tqdmG|ZTDBd5NigQ>? NWDjd5NnOSCq MVnEUXNQ M13XdmlvcGmkaYTpc44hd2ZiaIXtZY4hemWlb33ibY5idnRiYz3NSXQhc2mwYYPlJIV5eHKnc4Pl[EBie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGhITi2rbnT1Z4VlKGG3dH;wbI9{eGixconsZZRqd25id3n0bEBKSzVyIH;mJFAvODB6IN88US=> NXG3OmtNOjF6MUK0NVQ>
BAF3-BCL NEOyPINHfW6ldHnvckBCe3OjeR?= Ml74NUBp Mn\RSG1UVw>? NVPuToIyUW6qaXLpeIlwdiCxZjDBRmwh[XO|ZYPz[YQh[XNiZ4Lve5RpKG[jY4Tvdk1qdmS3Y3XkJIF2fG:yaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIEGuNVU6KM7:TR?= MWiyNVgyOjRzNB?=
HEK293 MoXvSpVv[3Srb36gRZN{[Xl? NWPJSm9xOSCq Mnz4SG1UVw>? MmrvTY5pcWKrdHnvckBw\iCDWFygZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwMkm0JO69VQ>? NHjCTo4zOThzMkSxOC=>
HEK293 MWrGeY5kfGmxbjDBd5NigQ>? NIjHW|kyKGh? M4TVUGROW09? M2nhUWlvcGmkaYTpc44hd2ZiSWKgZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDJwOEi3JO69VQ>? MUKyNVgyOjRzNB?=
Jurkat M4HVfGZ2dmO2aX;uJGF{e2G7 M1H4TFEhcA>? MoDqSG1UVw>? MknTTY5pcWKrdHnvckBw\iCOQ1ugZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDJwN{SxJO69VQ>? MnLhNlE5OTJ2MUS=
KARPAS299 MXXLbY5ie2ViQYPzZZk> M37TOlEhcA>? MnvJSG1UVw>? NHjWd2pKdmirYnn0bY9vKG:oIFHMT{Bie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6wNkDPxE1? Mn\4NlE5OTJ2MUS=
PAE MUDGeY5kfGmxbjDBd5NigQ>? MmP3NUBp MVfEUXNQ M{D2XmlvcGmkaYTpc44hd2ZiVGLLRkBie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6zPVkh|ryP NV\pTHNWOjF6MUK0NVQ>
BAF3 NGD1SINHfW6ldHnvckBCe3OjeR?= MWGyMVMh\A>? M2TicGROW09? NGHxN|RKdmirYnn0bY9vKG:oIGTFUE1nfXOnZDDpcpN2dGmwIILlZ4VxfG:{IHX4dJJme3OnZDD3bZRpKEmFNUCgc4YhOS54NEOg{txO NU\KWol5OjN5NEKyOVI>
KARPAS299 M3vLN2N6fG:2b4jpZ{BCe3OjeR?= NXz0VlF{Oi1|IHS= MVjEUXNQ Mn63TWM2OD1yLkC2OFIh|ryP MUKyN|c1OjJ3Mh?=
EBC1 NYXw[pNwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MonvO|IhcA>? MnS0SG1UVw>? NILSd2VKSzVyPUCuNFI{KM7:TR?= MVqyN|k6OzN{OB?=
HCT116 NFzzZ|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYHvNlVLPzJiaB?= MUDEUXNQ MYfJR|UxRTF2LkiyJO69VQ>? NWfhdWlROjN7OUOzNlg>
MCF7 MoDjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml\CO|IhcA>? MmXTSG1UVw>? NXXQUYdnUUN3ME25MlU5KM7:TR?= M2m4RVI{QTl|M{K4
MDA-MB-231 NGG4TolIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXO4Z|VMPzJiaB?= MmrmSG1UVw>? NXrQTZFbUUN3ME2xNE45KM7:TR?= M1PudFI{QTl|M{K4
MKN45 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{fqUFczKGh? MWnEUXNQ NE\TNnRKSzVyPUCuNFE{KM7:TR?= M2\SeFI{QTl|M{K4
NCI-H441 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3vlVFczKGh? M1\hV2ROW09? MX7JR|UxRTF5LkK1JO69VQ>? NUXMcWtoOjN7OUOzNlg>
NCI-H661 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUC3NkBp M1mwdWROW09? NFz5PGRKSzVyPUGxMlQ4KM7:TR?= MXyyN|k6OzN{OB?=
SK-MEL-28 NVPjclZyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mnj3O|IhcA>? M4LIb2ROW09? NWTGbJFwUUN3ME2xNE46PyEQvF2= MojJNlM6QTN|Mki=
SKOV3 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV:3NkBp NXqyXnhnTE2VTx?= NYnEXmNMUUN3ME2xNk45PSEQvF2= MYSyN|k6OzN{OB?=
SNU5 NXzJNZJCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4LjPVczKGh? M3W3WWROW09? NYK2dY5UUUN3ME2wMlAyPiEQvF2= Mkf5NlM6QTN|Mki=
NCI-H2228 MmXyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWK3NkBp NEXLRpBFVVOR NHj2R3JKdmirYnn0bY9vKG:oIFHMT{1nfXOrb36g[JJqfmWwIHPlcIwheHKxbHnm[ZJifGmxbjD3bZRpKEmFNUCgc4YhOC5zMUig{txO NVPUWFNyOjR2M{K5NFk>
NCI-H3122 M1LXSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mln0O|IhcA>? M4LjSWROW09? M3vNbGlvcGmkaYTpc44hd2ZiQVzLMYZ2e2mxbjDkdol3\W5iY3XscEBxem:uaX\ldoF1cW:wIIfpeIghUUN3MDDv[kAxNjFyODFOwG0> M2HBcVI1PDN{OUC5
NCI-H3122 MljsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVq3NkBp NYW5dGlLTE2VTx?= NF\vcnpKdmirYnn0bY9vKG:oIFHMT{1nfXOrb36g[JJqfmWwIHPlcIwheHKxbHnm[ZJifGmxbjDpckBpfW2jbjDOR2kuUDNzMkKgZ4VtdHNiaHHyZo9zcW6pIFHMT{BIOTJ4OVGgcZV1[W62IIfpeIghUUN3MDDv[kAxNjZ{MzFOwG0> NFfyNGYzPDR|MkmwPS=>
NCI-H3122 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH7zcXc4OiCq NXj0O3ZtTE2VTx?= NFvCU4lKdmirYnn0bY9vKG:oIFHMT{1nfXOrb36g[JJqfmWwIHPlcIwheHKxbHnm[ZJifGmxbjDpckBpfW2jbjDOR2kuUDNzMkKgZ4VtdHNiaHHyZo9zcW6pIFHMT{BNOTF7Nl2gcZV1[W62IIfpeIghUUN3MDDv[kAxNjh|ODFOwG0> NHPQOWUzPDR|MkmwPS=>
NIH-3T3 NEfDTYtMcW6jc3WgRZN{[Xl? NVriW5FrOSCq MnnZSG1UVw>? NGfoV2JKdmirYnn0bY9vKG:oIHj1cYFvKHerbHSgeJlx\SCHTVy0MYZ2e2WmIFHMT{BmgHC{ZYPz[YQh[XO|ZYPz[YQh[XNicHjvd5Bpd3K7bHH0[YQhSUyNIHzleoVtKHerdHigTWM2OCCxZjCwMlA5KM7:TR?= M1XkVlI1PDN{OUC5
NIH-3T3 NVLDV2Q2U2mwYYPlJGF{e2G7 MUexJIg> NXqwO4lkTE2VTx?= MlK0TY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzDHNVI3QUFibYX0ZY51KGW6cILld5Nm\CCjc4Pld5Nm\CCjczDwbI9{eGixLVHMT{Bt\X[nbDD3bZRpKEmFNUCgc4YhOC54MEWg{txO NH;me5kzPDR|MkmwPS=>
NIH-3T3 NV3hdZZUU2mwYYPlJGF{e2G7 M{Dj[|EhcA>? MXrEUXNQ MVrJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIGOxNlA3YSCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAxNjZ{NjFOwG0> NHHtNlgzPDR|MkmwPS=>
NIH-3T3 NHjCTHpMcW6jc3WgRZN{[Xl? NWfGZnFUOSCq MoHFSG1UVw>? NGPifGFKdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJGwyOTl4TTDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLki0N{DPxE1? MUOyOFQ{OjlyOR?=
NIH-3T3 NEm3WZdMcW6jc3WgRZN{[Xl? MmnkNUBp M4O2T2ROW09? NVy2PGZqUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BNOTF3MmKgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMT6wNlYh|ryP NXriZlJ7OjR2M{K5NFk>
BAF3 M1TNXWZ2dmO2aX;uJGF{e2G7 NEfsRmE4OiCq NXvpfWx7TE2VTx?= MWjJcohq[mm2aX;uJI9nKE6STT;BUGshfHKjboPm[YN1\WRiYYPz[ZN{\WRiYYOgZ4VtdCCpcn;3eIghcW6qaXLpeIlwdiC5aYToJGlEPTBib3[gNE4xPTFizszN M4Ln[|I1PDZ6NkOy
BAF3 MmfpR5l1d3SxeHnjJGF{e2G7 NGrld4M4OiCq NYfHVFRVTE2VTx?= M1rJWGlEPTB;MD65PEDPxE1? MYqyOFQ3QDZ|Mh?=
NIH-3T3 MVXLbY5ie2ViQYPzZZk> MnjzNUBp NVq3WZA{UW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BHOTF5NFygcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMD6xOlUh|ryP MXiyOFgyQTFzNh?=
NIH-3T3 MnvBT4lv[XOnIFHzd4F6 MlK2NUBp NXnYSXFzUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BEOTF3NmmgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMD60O|gh|ryP M3;4TlI1QDF7MUG2
NIH-3T3 NGf4SGpMcW6jc3WgRZN{[Xl? NUXl[5pVOSCq M2S5WWlvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugS|EzODKUIH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDFwMUS4JO69VQ>? NYf6fYNQOjR6MUmxNVY>
NIH-3T3 Ml:4T4lv[XOnIFHzd4F6 NXzoSHNTOSCq MXzJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIEGxOVFVcW6|IH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDNwMEO5JO69VQ>? NXfoXHI{OjR6MUmxNVY>
KARPAS299 M4LmTWtqdmG|ZTDBd5NigQ>? M4L5UlkxKG2rbh?= M2DqOWROW09? NVHIbmpyUW6qaXLpeIlwdiCxZjDOVG0u\nW|ZXSgRWxMKHCqb4PwbI9zgWyjdHnvckBmgHC{ZYPz[YQhf2m2aDDJR|UxKG:oIECuNVEh|ryP M33OcVI1QTByN{Ww
MKN 45 M{PhPGtqdmG|ZTDBd5NigQ>? M2Pse|EhcA>? MoH5SG1UVw>? NVjpeGZIUW6qaXLpeIlwdiCxZjDjMW1mfCCyaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIECuNFIh|ryP NW\aXYE3OjR7MEC3OVA>
A549 NVrLRnJQS3m2b4TvfIlkKEG|c3H5 MoHJOFghcA>? MUDEUXNQ M{jVcmlEPTBib3[gOE4xQDRizszN M2DzOFI1QTByOEOw
NCI-H1975 M2W5cGN6fG:2b4jpZ{BCe3OjeR?= MnfjOFghcA>? NYfBTXVETE2VTx?= NHTJUW9KSzVyIH;mJFcvPTVzIN88US=> MUKyOFkxODh|MB?=
NCI-H1993 M2nCXWN6fG:2b4jpZ{BCe3OjeR?= MVy0PEBp M37GU2ROW09? NYDOT2dSUUN3MDDv[kAxNjB4MTFOwG0> Mnn2NlQ6ODB6M{C=
NCI-H1993 NGL3emtCeG:2b4Ppd{BCe3OjeR?= NWrO[mRXOSEQvF2= NGO2eWwzPCCq M{TGN2ROW09? M3PuVoRw\XNibn;0JIlv\HWlZTDhdI9xfG:|aYO= NILIb4wzPDlyMEizNC=>
NIH-3T3 MYLDfZRwfG:6aXOgRZN{[Xl? M3XvN|Q5KGh? M4\jb2ROW09? MnTJTWM2OCCxZjCwMlM3PCEQvF2= MYqyOFkxODh|MB?=
EBC1 NGX1T49Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml63O|IhcA>? NFXr[XNFVVOR NGXVblJKSzVyIH;mJFAvODB4OTFOwG0> MknVNlQ6ODB6M{G=
KARPAS299 Mo\rS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYO3NkBp MnTCSG1UVw>? NXPWPYVTUUN3MDDv[kAxNjJizszN NVvmWI9YOjR7MEC4N|E>
NB1 NF;TdZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYjJR|UxRTlzLkm4JI5O NEjpS4ZUSU6JRWK=
NCI-SNU-5 M1\QNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVrJR|UxRTFyNT63OUBvVQ>? Mk\4V2FPT0WU
SR MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1XiVGlEPTB;MUK2MlMyKG6P NWrue5JmW0GQR1XS
SF539 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUDyOHpsUUN3ME2yNFQvOjRibl2= MXPTRW5ITVJ?
SU-DHL-1 M{\UUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NI\YVmlKSzVyPUOzOk45OiCwTR?= NIPacYRUSU6JRWK=
SCC-3 MmewS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoTFTWM2OD1|NU[uO|Yhdk1? M2nITXNCVkeHUh?=
DEL NFPVWW5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NI\R[JdKSzVyPUO2PU46KG6P M13ROnNCVkeHUh?=
CTV-1 NFjWN3hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVnJR|UxRTV7Nj60PEBvVQ>? MV;TRW5ITVJ?
EM-2 M1vCbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mny4TWM2OD14MEGuN|Qhdk1? NXjkUYR2W0GQR1XS
MHH-CALL-2 NWfVO|FPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mo\YTWM2OD14OEKuOVchdk1? M{T0VXNCVkeHUh?=
KM12 MlHKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NELPdmhKSzVyPUewOk46KG6P M1fBUHNCVkeHUh?=
KINGS-1 M1nmfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlzRTWM2OD15NEmuO|Uhdk1? MmXoV2FPT0WU
MEG-01 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NI\ieY9KSzVyPUi1O{43PiCwTR?= NXXCSHc2W0GQR1XS
BV-173 M{W2Z2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3izfWlEPTB;MT6wOVk6PyEQvF2= MmTVV2FPT0WU
LAMA-84 NWjRbVJFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYTMbGVoUUN3ME2xMlM5Ojh{IN88US=> NH7ueFFUSU6JRWK=
KARPAS-299 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWLJR|UxRTFwNEC4OlEh|ryP NHLPR3lUSU6JRWK=
K-562 NX60RWFKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYT1U3puUUN3ME2xMlczOjZ7IN88US=> M3LFPXNCVkeHUh?=
SK-LMS-1 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGDnZlFKSzVyPUGuO|Y5PjdizszN M1q0cXNCVkeHUh?=
MOLT-16 M1nkR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIDUSpVKSzVyPUGuPVU2PzVizszN Ml\KV2FPT0WU
CMK NYe4cmVkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3\pNWlEPTB;MT65OlE2QSEQvF2= NGm4ZW5USU6JRWK=
ST486 MlO0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVjJR|UxRTJwNEOwO|Mh|ryP MXLTRW5ITVJ?
CI-1 NWHMcGJmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkfQTWM2OD1{LkS5OlU6KM7:TR?= M4PQenNCVkeHUh?=
KP-N-RT-BM-1 M1rOUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWHqbW9XUUN3ME2yMlcxOTJ{IN88US=> M37Yc3NCVkeHUh?=
ALL-PO MmLYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2fFXWlEPTB;Mz6xPFIxPyEQvF2= NYD2XlRUW0GQR1XS
KS-1 NVLy[ZlZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWLJR|UxRTNwMkGyNlUh|ryP M3;Zd3NCVkeHUh?=
Becker M3LrWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4TpOmlEPTB;ND6yN|k{KM7:TR?= M{jnTXNCVkeHUh?=
GDM-1 NUjDUFl5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlPITWM2OD12LkK0OlE4KM7:TR?= M4jxb3NCVkeHUh?=
BC-1 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV[2S3d6UUN3ME20MlQ6Ojd5IN88US=> Mny4V2FPT0WU
NB14 NXnSfpdJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVrYT|JQUUN3ME20Mlg{PTJ2IN88US=> M1LhSHNCVkeHUh?=
NOS-1 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NG[1T3dKSzVyPUWuN|M5PzRizszN NXK3fYl2W0GQR1XS
MZ1-PC Moi2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml;yTWM2OD13LkiyNVUyKM7:TR?= NFLDUZZUSU6JRWK=
A498 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYDPXGhXUUN3ME22MlA5PDd|IN88US=> MX;TRW5ITVJ?
EW-16 MkK5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYW5VZcxUUN3ME22MlM4Pzd|IN88US=> M1Lad3NCVkeHUh?=
NALM-6 M1nHfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIjUTGlKSzVyPU[uOlg{QDdizszN NH20WmNUSU6JRWK=
EB-3 MnnFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NULqV|cyUUN3ME23MlA4OjN|IN88US=> MkPxV2FPT0WU
697 MoSxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2K0[GlEPTB;OT6yOFMzQSEQvF2= MVHTRW5ITVJ?
Ramos-2G6-4C10 NYi5coI2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3zEV2lEPTB;OT61PVg1OiEQvF2= NFjGXGNUSU6JRWK=
KNS-81-FD M1OwUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlvrTWM2OD17Lk[5OlU{KM7:TR?= MoLOV2FPT0WU
HUTU-80 MkPiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{TabWlEPTB;OT63OFY1OiEQvF2= MkLSV2FPT0WU
LS-411N MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHPU[lZKSzVyPUGwMlA2PjdizszN NH\IWppUSU6JRWK=
RPMI-8402 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MljDTWM2OD1zMD6xNVYh|ryP M2nYOnNCVkeHUh?=
KU812 M1LTWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVfJR|UxRTFyLkK5PVEh|ryP MmTRV2FPT0WU
EW-1 M4f1N2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M371SGlEPTB;MUCuOFQzPSEQvF2= NGrTT45USU6JRWK=
HC-1 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mm\hTWM2OD1zMD60PFQ1KM7:TR?= MmPWV2FPT0WU
NB69 NInJZ|hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWXJR|UxRTFyLkWwOFMh|ryP NWLwR3lLW0GQR1XS
MFH-ino M1XQdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUnJR|UxRTFyLkizNFMh|ryP MYnTRW5ITVJ?
CCRF-CEM MnX1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml25TWM2OD1zMT61PVch|ryP MoLjV2FPT0WU
SK-N-DZ M{HmXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV:5c5RLUUN3ME2xNk4xPDN4IN88US=> NIPMboRUSU6JRWK=
NCI-H720 NH;WNXFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUHJR|UxRTF{LkG3NFUh|ryP NVvnR2NuW0GQR1XS
HCC1187 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXn4bGtGUUN3ME2xNk4zODRzIN88US=> MUTTRW5ITVJ?
IST-SL2 M1y5cmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXPJR|UxRTF{LkS4O|Ih|ryP MmOwV2FPT0WU
KE-37 M2PKRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1e5VGlEPTB;MUKuO|k3PiEQvF2= NYPLW2RrW0GQR1XS
HCC1599 M4Dk[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIftb|RKSzVyPUGyMlkxPjlizszN MVXTRW5ITVJ?
A4-Fuk NUfwS4VkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWPJR|UxRTF{Lkm1PFYh|ryP NGfNZ5pUSU6JRWK=
NKM-1 NWDPVWoyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn3VTWM2OD1zMz6yPVI2KM7:TR?= NFn3b5NUSU6JRWK=
BE-13 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1LF[GlEPTB;MUOuO|k5QSEQvF2= MWjTRW5ITVJ?
MV-4-11 NXH4TFc1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUG1PWdVUUN3ME2xOE4xOzJ2IN88US=> NH34cG9USU6JRWK=
OPM-2 NUXLNVRTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFPTPWZKSzVyPUG0MlQxQDVizszN MVPTRW5ITVJ?
KARPAS-422 M2nucGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MY\JR|UxRTF2LkWxNlYh|ryP MVvTRW5ITVJ?
RPMI-8226 M3;GSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NETm[XpKSzVyPUG0Mlg6OTVizszN NVftbW1XW0GQR1XS
KARPAS-45 NUDlTlVCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MknaTWM2OD1zNT63O|E3KM7:TR?= MX3TRW5ITVJ?
SK-PN-DW MlT2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXz1OZd{UUN3ME2xOU45PjNzIN88US=> MVXTRW5ITVJ?
LC-2 M17OO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF3WPGxKSzVyPUG2MlE2ODZizszN NFXC[JpUSU6JRWK=
NCI-H1648 MmjBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{PXWWlEPTB;MU[uNlU1KM7:TR?= NEXvcJFUSU6JRWK=
RL95-2 M2nxZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3XsfmlEPTB;MU[uN|k4QCEQvF2= MlTDV2FPT0WU
KNS-42 NEPLfYVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NILPVXNKSzVyPUG2MlczPzRizszN NYPxZYlxW0GQR1XS
RPMI-6666 NFTOe|FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkHOTWM2OD1zNj65NlEyKM7:TR?= NHrM[YJUSU6JRWK=
SIG-M5 MoXtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3zDT2lEPTB;MUeuNVkxOyEQvF2= MUjTRW5ITVJ?
VA-ES-BJ NY\YW4RRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MY\JR|UxRTF5Lke0OVEh|ryP M33POnNCVkeHUh?=
MONO-MAC-6 M{Oyemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV;r[WtWUUN3ME2xO{46OzF{IN88US=> NWrPVFM3W0GQR1XS
LAN-6 NV7INGlNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYjJR|UxRTF6Lke1OVch|ryP MkfVV2FPT0WU
A388 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXTJR|UxRTF7LkOwOVkh|ryP MmXaV2FPT0WU
SK-NEP-1 NIPV[VdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHnTeJpKSzVyPUKwMlIyOzJizszN MVjTRW5ITVJ?
TE-10 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXHSfG9LUUN3ME2yNE42OjJzIN88US=> MXTTRW5ITVJ?
HL-60 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M373PGlEPTB;MkCuPVA6QSEQvF2= NXW2TnE4W0GQR1XS
MC116 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M33nW2lEPTB;MkGuO|IzOSEQvF2= NIjtZXNUSU6JRWK=
SW962 NWLROnpXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVrJR|UxRTJzLke5NVUh|ryP MWLTRW5ITVJ?
NOMO-1 NHf0eWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYjhN4NRUUN3ME2yNk43PTZ2IN88US=> MW\TRW5ITVJ?
CTB-1 MmLwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{L1e2lEPTB;MkKuPFY4OSEQvF2= NWTqeo53W0GQR1XS
MRK-nu-1 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoDHTWM2OD1{Mj65NFc1KM7:TR?= M4rLVXNCVkeHUh?=
GR-ST NHHBSGJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkDKTWM2OD1{Mz63OkDPxE1? NF72R4JUSU6JRWK=
HH NEjMVpBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmO5TWM2OD1{ND6wNFMh|ryP NFHt[phUSU6JRWK=
NCI-H1963 NYX2S2ZGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVz3Z21xUUN3ME2yOE4xPzh{IN88US=> Mmi4V2FPT0WU
QIMR-WIL MkDIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXnEZ295UUN3ME2yOE45Pzd{IN88US=> NFLwOYtUSU6JRWK=
CGTH-W-1 MlWwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIHnWJhKSzVyPUK1MlA4OjNizszN MkX1V2FPT0WU
LP-1 MkH4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoPQTWM2OD1{NT62OVUyKM7:TR?= MXfTRW5ITVJ?
NCI-H748 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{nreGlEPTB;Mk[uOVE{PyEQvF2= M{f5N3NCVkeHUh?=
PF-382 M3HyT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWHJR|UxRTJ5LkKyNlMh|ryP M4XBXnNCVkeHUh?=
ATN-1 M2W2c2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkHZTWM2OD1{Nz6zO|MzKM7:TR?= MUTTRW5ITVJ?
L-540 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXm1Wlh6UUN3ME2yO{43PDV7IN88US=> NYHsSGpzW0GQR1XS
LXF-289 MnXtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYHDN5U2UUN3ME2yO{44PTF7IN88US=> MmXFV2FPT0WU
LS-513 M33WSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlLYTWM2OD1{OD6xPFA4KM7:TR?= NVrLOlc2W0GQR1XS
NCI-H1581 NFHGTIpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGrhOnNKSzVyPUOwMlM6PzZizszN NGWxcZFUSU6JRWK=
ES6 M4TzdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlXlTWM2OD1|MD62PFk6KM7:TR?= MVLTRW5ITVJ?
SW982 NV6wbm5TT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWPJR|UxRTNyLki1OlYh|ryP NFGx[2JUSU6JRWK=
DOHH-2 M2TEXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFKyN2RKSzVyPUOxMlU5QTNizszN M1rXZXNCVkeHUh?=
DB NGDBNFVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYPBdmF3UUN3ME2zN{46PDNzIN88US=> NEG2eGxUSU6JRWK=
MPP-89 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmfFTWM2OD1|ND6xO|U3KM7:TR?= NIHGSnFUSU6JRWK=
LB831-BLC M13LWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnfRTWM2OD1|ND61NVg1KM7:TR?= NIXycWdUSU6JRWK=
NB5 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVLJR|UxRTN2Lki1N|Uh|ryP Mnf1V2FPT0WU
GB-1 NYPCS5poT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGfPWpJKSzVyPUO1MlA1PjlizszN NUn6WWhiW0GQR1XS
TE-15 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEC4PI1KSzVyPUO1MlIzOzhizszN MmO4V2FPT0WU
LC4-1 NFjROFBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIrXVnlKSzVyPUO1MlM5PDdizszN NH\TdHRUSU6JRWK=
NCI-H747 MoTzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIPSToRKSzVyPUO2MlE{PjlizszN NWTyUpdJW0GQR1XS
NTERA-S-cl-D1 NFe0dmtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnzSTWM2OD1|OD63N|Q4KM7:TR?= MXzTRW5ITVJ?
SK-MM-2 M1XoVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYHJR|UxRTRyLkGxOFYh|ryP NUCyZYsxW0GQR1XS
TGW MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVPzRo9qUUN3ME20NU4xPTZ|IN88US=> Moi2V2FPT0WU
ONS-76 NEGzeZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NI[2bVhKSzVyPUSyMlQ5QDNizszN NV3repJqW0GQR1XS
CPC-N M3LPXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUXJR|UxRTR{Lkm5O|Eh|ryP MVLTRW5ITVJ?
ES4 NVvifYlKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXzJR|UxRTR2LkSxOVMh|ryP NUX6Om16W0GQR1XS
Daudi MlvZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX7s[Gp3UUN3ME20OU4xQDJ5IN88US=> MYHTRW5ITVJ?
MOLT-4 MnvQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnX5TWM2OD12NT6wPFU{KM7:TR?= NVuydFdiW0GQR1XS
HT-144 NXTweZBZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXq1R3BFUUN3ME20Ok44OjZizszN NYDrd5RkW0GQR1XS
SW872 MnvhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEDyPWdKSzVyPUS4MlE6OzNizszN Mn3EV2FPT0WU
D-283MED NYfuNFFJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVHielhiUUN3ME20PE4{PTR{IN88US=> MWfTRW5ITVJ?
NCI-H2126 NXPuT4dQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmLuTWM2OD12OD64OFc3KM7:TR?= NEjEWGtUSU6JRWK=
NCI-SNU-16 Mn:2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYT2U|h1UUN3ME20PU4zOTR|IN88US=> MXHTRW5ITVJ?
CESS M1vwe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NILJPYRKSzVyPUS5MlUxQDhizszN NWTNOWEzW0GQR1XS
A101D NFXtbmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX3ROlVNUUN3ME20PU46PzN4IN88US=> MVfTRW5ITVJ?

... 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
  • Formulation: --
  • 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(OC1=C(N)N=CC(=C1)C2=C[N](N=C2)C3CCNCC3)C4=C(Cl)C=CC(=C4Cl)F

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
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 Recruiting 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
NCT02510001 Active not recruiting Drug: PF-02341066|Drug: PD-0325901|Drug: Binimetinib Solid Tumor|Colorectal Cancer University of Oxford|Queen''s University Belfast|Oxford University Hospitals NHS Trust|Velindre NHS Trust|University Hospital Antwerp|Hospital Vall d''Hebron|Saint Antoine University Hospital|European Georges Pompidou Hospital|Pfizer|University of Turin Italy|Belfast Health and Social Care Trust|Beaumont Hospital|European Commission|Array BioPharma|University of Paris 5 - Rene Descartes November 2014 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.

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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