Crizotinib (PF-02341066)

Licensed by Pfizer Catalog No.S1068

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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Cited by 88 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 MmHLR5l1d3SxeHnjJGF{e2G7 MlixOFghcA>? MXLEUXNQ MWLDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRWY{KGOnbHzzJIV5eHKnc4PpcochSUyNIF[xNVc1VCCvdYThcpQh[2:neIDy[ZN{cW6pIFXNUFQhf2m2aDDJR|UxKG:oIECuOlIh|ryP M1i1UFIyPTd{NUi5
BAF3 NF\YcGVEgXSxdH;4bYMhSXO|YYm= M{PYVFQ5KGh? M1ewR2ROW09? NF\C[opEgXSxdH;4bYNqfHliYXfhbY5{fCCvb4Xz[UBDSUZ|IHPlcIx{KGW6cILld5NqdmdiQVzLJGwyOTl4TTDteZRidnRiY3;lfJBz\XO|aX7nJGVOVDRid3n0bEBKSzVyIH;mJFIvOiEQvF2= M2D2XFIyPTd{NUi5
BAF3 MXrDfZRwfG:6aXOgRZN{[Xl? MnnTOFghcA>? MnrtSG1UVw>? MoTSR5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmFHOyClZXzsd{BmgHC{ZYPzbY5oKEWPTEStRWxMKHerdHigTWM2OCCxZjCwMlI5KM7:TR?= M1SwWVIyPTd{NUi5
Kelly MXjDfZRwfG:6aXOgRZN{[Xl? Mn3iSG1UVw>? Mni4R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gT4VtdHliY3XscJMh\XiycnXzd4lv\yCDTFugSlEyPzSOIH31eIFvfCC5aYToJGlEPTBib3[gNE41OiEQvF2= MnjPNlE2PzJ3OEm=
SH-SY5Y MWjDfZRwfG:6aXOgRZN{[Xl? MlTpSG1UVw>? M4flTWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHNJNVO\NWmgZ4VtdHNiZYjwdoV{e2mwZzDBUGshTjFzN{TMJI12fGGwdDD3bZRpKEmFNUCgc4YhOC53MzFOwG0> MX[yNVU4OjV6OR?=
SMS-KCN M1;odWN6fG:2b4jpZ{BCe3OjeR?= M13xUGROW09? NEW0R45EgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBUVVNvS1POJINmdGy|IHX4dJJme3OrbnegRWxMKFJzMke1VUBufXSjboSge4l1cCCLQ{WwJI9nKDBwOUGg{txO NIK5fFIzOTV5MkW4PS=>
BAF3 NHXMU4dEgXSxdH;4bYMhSXO|YYm= NFXI[FM1QCCq NYPJblZCTE2VTx?= NYrUVnRHS3m2b4TvfIlkcXS7IHHnZYlve3RibX;1d4UhSkGIMzDj[YxteyCneIDy[ZN{cW6pIGTlcE1CVEtid3n0bEBKSzVyIH;mJFAvOTlizszN Mn7qNlE2PzJ3OEm=
3T3 NYL1PGhWTnWwY4Tpc44hSXO|YYm= MlfDNUBp NVm0[|FkTE2VTx?= MULJcohq[mm2aX;uJI9nKFKRTjDhd5Nme3OnZDDhd{Boem:5dHig[oFkfG:{LXnu[JVk\WRiYYX0c5Bpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOC5yODFOwG0> MnPpNlE5OTJ2MUS=
3T3-E NEm5eHhHfW6ldHnvckBCe3OjeR?= MX[xJIg> M4PHcGROW09? MUnJcohq[mm2aX;uJI9nKFSLRUKgZZN{\XO|ZXSg[5Jwf3SqIH\hZ5Rwei2rbnT1Z4VlKGG3dH;wbI9{eGixconsZZRqd25id3n0bEBKSzVyIH;mJFAvPDR6IN88US=> NELKbFIzOThzMkSxOC=>
A549 MUPLbY5ie2ViQYPzZZk> MVixJIg> M2Wx[WROW09? MVjJcohq[mm2aX;uJI9nKGi3bXHuJJJm[2:vYnnuZY51KGNvTVXUJItqdmG|ZTDlfJBz\XO|ZXSgZZN{\XO|ZXSgZZMhcW6qaXLpeIlwdiCxZjDIS2YucW6mdXPl[EBifXSxcHjvd5Bpd3K7bHH0bY9vKHerdHigTWM2OCCxZjCwMlAxQCEQvF2= NUf0[IE1OjF6MUK0NVQ>
BAF3-BCL NYG3WHo2TnWwY4Tpc44hSXO|YYm= M1LWZ|EhcA>? M4Hsd2ROW09? M{nBSGlvcGmkaYTpc44hd2ZiQVLMJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iBzLkG1PUDPxE1? MUWyNVgyOjRzNB?=
HEK293 M{O2NGZ2dmO2aX;uJGF{e2G7 NX\w[pE5OSCq MlPRSG1UVw>? NXTNVYhQUW6qaXLpeIlwdiCxZjDBXGwh[XO|ZYPz[YQh[XNiZ4Lve5RpKG[jY4Tvdk1qdmS3Y3XkJIF2fG:yaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIECuNlk1KM7:TR?= MYWyNVgyOjRzNB?=
HEK293 NFzH[HFHfW6ldHnvckBCe3OjeR?= M2f3clEhcA>? NFTJeWhFVVOR MVPJcohq[mm2aX;uJI9nKEmUIHHzd4V{e2WmIHHzJIdzd3e2aDDmZYN1d3JvaX7keYNm\CCjdYTvdIhwe3Cqb4L5cIF1cW:wIIfpeIghUUN3MDDv[kAzNjh6NzFOwG0> NG\nZnQzOThzMkSxOC=>
Jurkat MXfGeY5kfGmxbjDBd5NigQ>? MkHNNUBp MlXYSG1UVw>? Ml\pTY5pcWKrdHnvckBw\iCOQ1ugZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDJwN{SxJO69VQ>? MnLENlE5OTJ2MUS=
KARPAS299 MlvXT4lv[XOnIFHzd4F6 NV3wVXIxOSCq NGS0TWpFVVOR NY\aUnk5UW6qaXLpeIlwdiCxZjDBUGsh[XO|ZYPz[YQh[XNiZ4Lve5RpKG[jY4Tvdk1qdmS3Y3XkJIF2fG:yaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIECuNFIh|ryP MmDKNlE5OTJ2MUS=
PAE NFLqRm9HfW6ldHnvckBCe3OjeR?= NVrjd3VnOSCq MY\EUXNQ Mnv4TY5pcWKrdHnvckBw\iCWUlvCJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iByLkO5PUDPxE1? NIrWNGczOThzMkSxOC=>
BAF3 NGfDSlRHfW6ldHnvckBCe3OjeR?= NFnwb2UzNTNiZB?= NUi0TmtNTE2VTx?= M2fjUmlvcGmkaYTpc44hd2ZiVFXMMYZ2e2WmIHnud5VtcW5icnXj[ZB1d3JiZYjwdoV{e2WmIIfpeIghUUN3MDDv[kAyNjZ2MzFOwG0> M1XsTlI{PzR{MkWy
KARPAS299 Ml3rR5l1d3SxeHnjJGF{e2G7 MXuyMVMh\A>? Mn7ISG1UVw>? MlizTWM2OD1yLkC2OFIh|ryP NWm4[G9XOjN5NEKyOVI>
EBC1 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVK3NkBp NV60bm1iTE2VTx?= NUPLd4tiUUN3ME2wMlAzOyEQvF2= MmO1NlM6QTN|Mki=
HCT116 NIX4UmxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnjOO|IhcA>? MWHEUXNQ NI\jRZZKSzVyPUG0MlgzKM7:TR?= M1r1UVI{QTl|M{K4
MCF7 M17wdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGPGe4I4OiCq M1;B[mROW09? NYTFNpJCUUN3ME25MlU5KM7:TR?= NFf4R5YzOzl7M{OyPC=>
MDA-MB-231 NXPOTXZwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1nKb|czKGh? M37SXWROW09? M4GxXWlEPTB;MUCuPEDPxE1? NV7WeXpLOjN7OUOzNlg>
MKN45 Mnz5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUG3NkBp MVTEUXNQ M3r4bGlEPTB;MD6wNVMh|ryP MY[yN|k6OzN{OB?=
NCI-H441 MkLES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlHPO|IhcA>? M{HxcmROW09? MojtTWM2OD1zNz6yOUDPxE1? NVzmfHJoOjN7OUOzNlg>
NCI-H661 NFf3epFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn3tO|IhcA>? M3S0RmROW09? MnzyTWM2OD1zMT60O{DPxE1? MnPnNlM6QTN|Mki=
SK-MEL-28 NH;3SnlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoXJO|IhcA>? M13CfmROW09? NELMTWhKSzVyPUGwMlk4KM7:TR?= NEjmfY0zOzl7M{OyPC=>
SKOV3 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M37EOVczKGh? MYfEUXNQ NV7nTGdLUUN3ME2xNk45PSEQvF2= MUSyN|k6OzN{OB?=
SNU5 M1jGWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHGx[|M4OiCq MV\EUXNQ MWnJR|UxRTBwMEG2JO69VQ>? NVO2XGZoOjN7OUOzNlg>
NCI-H2228 MknpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkTWO|IhcA>? M4nvVmROW09? NFXyOI9KdmirYnn0bY9vKG:oIFHMT{1nfXOrb36g[JJqfmWwIHPlcIwheHKxbHnm[ZJifGmxbjD3bZRpKEmFNUCgc4YhOC5zMUig{txO NXLMd41rOjR2M{K5NFk>
NCI-H3122 NHG4bIlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NG\JXZg4OiCq MVzEUXNQ NVj0ZZBsUW6qaXLpeIlwdiCxZjDBUGsu\nW|aX;uJIRzcX[nbjDj[YxtKHC{b3zp[oVz[XSrb36ge4l1cCCLQ{WwJI9nKDBwMUC4JO69VQ>? NV3SNHpWOjR2M{K5NFk>
NCI-H3122 NH3DSWdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXjUVIF[PzJiaB?= M3i5Z2ROW09? M4jsS2lvcGmkaYTpc44hd2ZiQVzLMYZ2e2mxbjDkdol3\W5iY3XscEBxem:uaX\ldoF1cW:wIHnuJIh2dWGwIF7DTU1JOzF{MjDj[YxteyCqYYLic5JqdmdiQVzLJGcyOjZ7QTDteZRidnRid3n0bEBKSzVyIH;mJFAvPjJ|IN88US=> NXfZ[5R3OjR2M{K5NFk>
NCI-H3122 MoC4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmT2O|IhcA>? NGLqfnpFVVOR NYLRZ49ZUW6qaXLpeIlwdiCxZjDBUGsu\nW|aX;uJIRzcX[nbjDj[YxtKHC{b3zp[oVz[XSrb36gbY4hcHWvYX6gUmNKNUh|MUKyJINmdGy|IHjhdoJwemmwZzDBUGshVDFzOU\NJI12fGGwdDD3bZRpKEmFNUCgc4YhOC56M{ig{txO MV2yOFQ{OjlyOR?=
NIH-3T3 M3rt[WtqdmG|ZTDBd5NigQ>? M{PvOlEhcA>? NITr[FFFVVOR NVXiUYdvUW6qaXLpeIlwdiCxZjDoeY1idiC5aXzkJJR6eGViRV3MOE1nfXOnZDDBUGsh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG:{eXzheIVlKEGOSzDs[ZZmdCC5aYToJGlEPTBib3[gNE4xQCEQvF2= MlzhNlQ1OzJ7MEm=
NIH-3T3 NFG1TXNMcW6jc3WgRZN{[Xl? M3m0TVEhcA>? M1fZRWROW09? NEfMT|NKdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJGcyOjZ7QTDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLk[wOUDPxE1? MVmyOFQ{OjlyOR?=
NIH-3T3 NHW0WolMcW6jc3WgRZN{[Xl? MXyxJIg> Mmi2SG1UVw>? MUXJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIGOxNlA3YSCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAxNjZ{NjFOwG0> NYLzUmd6OjR2M{K5NFk>
NIH-3T3 M2XOSGtqdmG|ZTDBd5NigQ>? M4PWOVEhcA>? MXTEUXNQ NED4NndKdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJGwyOTl4TTDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLki0N{DPxE1? NFLVXJozPDR|MkmwPS=>
NIH-3T3 MWLLbY5ie2ViQYPzZZk> MUCxJIg> M1PZO2ROW09? NUiwOpUxUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BNOTF3MmKgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMT6wNlYh|ryP NF7aUmozPDR|MkmwPS=>
BAF3 Moe2SpVv[3Srb36gRZN{[Xl? NX7KWWh5PzJiaB?= MoHqSG1UVw>? M2rpW2lvcGmkaYTpc44hd2ZiTmDNM2FNUyC2cnHud4Zm[3SnZDDhd5Nme3OnZDDhd{Bk\WyuIHfyc5d1cCCrbnjpZol1cW:wIIfpeIghUUN3MDDv[kAxNjB3MTFOwG0> MlzRNlQ1Pjh4M{K=
BAF3 NUXHPY5lS3m2b4TvfIlkKEG|c3H5 MWm3NkBp NV\DZ5k4TE2VTx?= MlnVTWM2OD1yLkm4JO69VQ>? MorCNlQ1Pjh4M{K=
NIH-3T3 M2j1WGtqdmG|ZTDBd5NigQ>? MXixJIg> NE\BSVZKdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJGYyOTd2TDDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLkG2OUDPxE1? M4nHZVI1QDF7MUG2
NIH-3T3 NVPJW3FCU2mwYYPlJGF{e2G7 NUnoeoRwOSCq NEXXOW9KdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJGMyOTV4WTDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLkS3PEDPxE1? Mm\INlQ5OTlzMU[=
NIH-3T3 NXXHS5pEU2mwYYPlJGF{e2G7 Mnu4NUBp M1;zSGlvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugS|EzODKUIH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDFwMUS4JO69VQ>? MmrpNlQ5OTlzMU[=
NIH-3T3 NELh[|dMcW6jc3WgRZN{[Xl? MmDVNUBp NVz2[lJIUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{AyOTVzVHnud{BufXSjboSg[ZhxemW|c3XkJIF{e2W|c3XkJIF{KHCqb4PwbI8uSUyNIHzleoVtKHerdHigTWM2OCCxZjCzMlA{QSEQvF2= MYCyOFgyQTFzNh?=
KARPAS299 M3jITmtqdmG|ZTDBd5NigQ>? NXOyO4ltQTBibXnu NEnhUI5FVVOR NXvJWY9uUW6qaXLpeIlwdiCxZjDOVG0u\nW|ZXSgRWxMKHCqb4PwbI9zgWyjdHnvckBmgHC{ZYPz[YQhf2m2aDDJR|UxKG:oIECuNVEh|ryP NYH2TJd4OjR7MEC3OVA>
MKN 45 NVG0Xnc2U2mwYYPlJGF{e2G7 MXuxJIg> NVjOR49mTE2VTx?= MXrJcohq[mm2aX;uJI9nKGNvTXX0JJBpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOC5yMjFOwG0> MUCyOFkxODd3MB?=
A549 MmnWR5l1d3SxeHnjJGF{e2G7 NIPwO|g1QCCq MWTEUXNQ M2LF[2lEPTBib3[gOE4xQDRizszN NU\weWU5OjR7MEC4N|A>
NCI-H1975 MlT4R5l1d3SxeHnjJGF{e2G7 NETvN3g1QCCq MYHEUXNQ NYrL[oNlUUN3MDDv[kA4NjV3MTFOwG0> MU[yOFkxODh|MB?=
NCI-H1993 NXK4W|JrS3m2b4TvfIlkKEG|c3H5 NXvrdVRUPDhiaB?= NFfaVWlFVVOR NGjEXYJKSzVyIH;mJFAvODZzIN88US=> MnPDNlQ6ODB6M{C=
NCI-H1993 NVrl[mFxSXCxdH;zbZMhSXO|YYm= MkPhNUDPxE1? NHm1clUzPCCq M170UmROW09? MV3kc4V{KG6xdDDpcoR2[2ViYYDvdJRwe2m| MYOyOFkxODh|MB?=
NIH-3T3 NYPhR4UzS3m2b4TvfIlkKEG|c3H5 NHP1[pI1QCCq M2TpRWROW09? MUTJR|UxKG:oIECuN|Y1KM7:TR?= MmPzNlQ6ODB6M{C=
EBC1 MnLLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV3KZldTPzJiaB?= MVXEUXNQ M1yySGlEPTBib3[gNE4xODZ7IN88US=> NGLDRYIzPDlyMEizNS=>
KARPAS299 Mn3nS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFHPT|M4OiCq NYrWdYVQTE2VTx?= NFm4TohKSzVyIH;mJFAvOiEQvF2= NIH6VWkzPDlyMEizNS=>
NB1 M2fBWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmXhTWM2OD17MT65PEBvVQ>? M1nwXXNCVkeHUh?=
NCI-SNU-5 M2XTUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NInJTlNKSzVyPUGwOU44PSCwTR?= NH;keWZUSU6JRWK=
SR NGnoWolIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXK4WGg2UUN3ME2xNlYvOzFibl2= MYjTRW5ITVJ?
SF539 NYTqR|Z7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NE\3TJdKSzVyPUKwOE4zPCCwTR?= MmjxV2FPT0WU
SU-DHL-1 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2Pke2lEPTB;M{O2MlgzKG6P M3nBPHNCVkeHUh?=
SCC-3 NXzYOW5PT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYjJR|UxRTN3Nj63OkBvVQ>? MnL1V2FPT0WU
DEL NYXkTZhHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUjJR|UxRTN4OT65JI5O NHX1eW9USU6JRWK=
CTV-1 NILPcI1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUTJR|UxRTV7Nj60PEBvVQ>? NFjCWIJUSU6JRWK=
EM-2 NGrTR3ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUK1[W15UUN3ME22NFEvOzRibl2= NFHzWY1USU6JRWK=
MHH-CALL-2 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3PE[WlEPTB;NkiyMlU4KG6P MX3TRW5ITVJ?
KM12 NFLG[5hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2n1OmlEPTB;N{C2Mlkhdk1? M13jTHNCVkeHUh?=
KINGS-1 NXPnSplbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWPlSYx2UUN3ME23OFkvPzVibl2= M13SN3NCVkeHUh?=
MEG-01 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYPJR|UxRTh3Nz62OkBvVQ>? M4r2SnNCVkeHUh?=
BV-173 NH\L[ZhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MknrTWM2OD1zLkC1PVk4KM7:TR?= MVXTRW5ITVJ?
LAMA-84 NFzPd5hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MW\JR|UxRTFwM{iyPFIh|ryP NIrrN5ZUSU6JRWK=
KARPAS-299 M2jWXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXzOcYg3UUN3ME2xMlQxQDZzIN88US=> NW[5W|ZGW0GQR1XS
K-562 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnPNTWM2OD1zLkeyNlY6KM7:TR?= MnP3V2FPT0WU
SK-LMS-1 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX7JR|UxRTFwN{[4Olch|ryP NICz[IJUSU6JRWK=
MOLT-16 MkjZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mmr0TWM2OD1zLkm1OVc2KM7:TR?= MU\TRW5ITVJ?
CMK MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUTJR|UxRTFwOU[xOVkh|ryP MXrTRW5ITVJ?
ST486 NYjvPHY1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXrJR|UxRTJwNEOwO|Mh|ryP NYjoU5JKW0GQR1XS
CI-1 M1\Be2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXXL[nRYUUN3ME2yMlQ6PjV7IN88US=> MVvTRW5ITVJ?
KP-N-RT-BM-1 M4Lk[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1z3OWlEPTB;Mj63NFEzOiEQvF2= NYLETWdJW0GQR1XS
ALL-PO M{LHWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MY\JR|UxRTNwMUiyNFch|ryP NIHzOolUSU6JRWK=
KS-1 NHjVOm5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlTMTWM2OD1|LkKxNlI2KM7:TR?= NXiwUHlYW0GQR1XS
Becker MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoDGTWM2OD12LkKzPVMh|ryP MkG4V2FPT0WU
GDM-1 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGDZOXlKSzVyPUSuNlQ3OTdizszN MVnTRW5ITVJ?
BC-1 MormS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUHjc2tRUUN3ME20MlQ6Ojd5IN88US=> MWfTRW5ITVJ?
NB14 NEHieYJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGLPZXlKSzVyPUSuPFM2OjRizszN M4njeXNCVkeHUh?=
NOS-1 NXPXVYVHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4HVfWlEPTB;NT6zN|g4PCEQvF2= M{XpfnNCVkeHUh?=
MZ1-PC NX7DfFR7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVPJR|UxRTVwOEKxOVEh|ryP NFWwTIlUSU6JRWK=
A498 NH\5fZdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2rESWlEPTB;Nj6wPFQ4OyEQvF2= M3yzSXNCVkeHUh?=
EW-16 NGTOU4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHzzfJdKSzVyPU[uN|c4PzNizszN NICxcWNUSU6JRWK=
NALM-6 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGrFdmJKSzVyPU[uOlg{QDdizszN M3f4WXNCVkeHUh?=
EB-3 NELmSnlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHjZOW9KSzVyPUeuNFczOzNizszN MljNV2FPT0WU
697 MlTwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MorqTWM2OD17LkK0N|I6KM7:TR?= NFXjVGZUSU6JRWK=
Ramos-2G6-4C10 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2TUXGlEPTB;OT61PVg1OiEQvF2= MVHTRW5ITVJ?
KNS-81-FD M1rsUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWHJR|UxRTlwNkm2OVMh|ryP NH72S41USU6JRWK=
HUTU-80 NVPwflY5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWTJR|UxRTlwN{S2OFIh|ryP MYXTRW5ITVJ?
LS-411N M{TscWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1ntVWlEPTB;MUCuNFU3PyEQvF2= MWHTRW5ITVJ?
RPMI-8402 M1P4UGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHjjS2xKSzVyPUGwMlEyPiEQvF2= NXu4eIxHW0GQR1XS
KU812 NETaUmtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIq0R2VKSzVyPUGwMlI6QTFizszN NVjXcZJPW0GQR1XS
EW-1 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFH5VGJKSzVyPUGwMlQ1OjVizszN MWrTRW5ITVJ?
HC-1 M4fESmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlrJTWM2OD1zMD60PFQ1KM7:TR?= NFvGXJJUSU6JRWK=
NB69 M{X5Vmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn7MTWM2OD1zMD61NFQ{KM7:TR?= M1zrfHNCVkeHUh?=
MFH-ino MkXzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkLKTWM2OD1zMD64N|A{KM7:TR?= MW\TRW5ITVJ?
CCRF-CEM NXjod|lET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFLob2RKSzVyPUGxMlU6PyEQvF2= M4ezcHNCVkeHUh?=
SK-N-DZ MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmHPTWM2OD1zMj6wOFM3KM7:TR?= NH3yemdUSU6JRWK=
NCI-H720 NEPUTWdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEnBeGRKSzVyPUGyMlE4ODVizszN NYfCZmxVW0GQR1XS
HCC1187 NFvtR|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWTPbG0zUUN3ME2xNk4zODRzIN88US=> MoiyV2FPT0WU
IST-SL2 M3myeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX;hdlg4UUN3ME2xNk41QDd{IN88US=> MYfTRW5ITVJ?
KE-37 M1PYV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFKxNmlKSzVyPUGyMlc6PjZizszN NXX1VnVEW0GQR1XS
HCC1599 M4DlNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmG3TWM2OD1zMj65NFY6KM7:TR?= M1Hs[nNCVkeHUh?=
A4-Fuk M{ft[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXHKZXUxUUN3ME2xNk46PTh4IN88US=> NF63N2tUSU6JRWK=
NKM-1 Ml\tS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4jwb2lEPTB;MUOuNlkzPSEQvF2= MUjTRW5ITVJ?
BE-13 M3m4R2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVnJR|UxRTF|Lke5PFkh|ryP M1n4b3NCVkeHUh?=
MV-4-11 NWjDS|FJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2D1TGlEPTB;MUSuNFMzPCEQvF2= NFvB[ZFUSU6JRWK=
OPM-2 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MljhTWM2OD1zND60NFg2KM7:TR?= NGDCSmRUSU6JRWK=
KARPAS-422 NFfGc2tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIHLWGhKSzVyPUG0MlUyOjZizszN MnnXV2FPT0WU
RPMI-8226 M{DLOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4TIO2lEPTB;MUSuPFkyPSEQvF2= MYTTRW5ITVJ?
KARPAS-45 NGnr[nFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH24dJFKSzVyPUG1Mlc4OTZizszN NGnGOJdUSU6JRWK=
SK-PN-DW NUPvSIY3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEL5UHlKSzVyPUG1Mlg3OzFizszN NWe2UJRwW0GQR1XS
LC-2 MkjkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFHhXFBKSzVyPUG2MlE2ODZizszN NGm5SllUSU6JRWK=
NCI-H1648 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIXDVVhKSzVyPUG2MlI2PCEQvF2= MnTjV2FPT0WU
RL95-2 MnrXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWXCfFRGUUN3ME2xOk4{QTd6IN88US=> MWHTRW5ITVJ?
KNS-42 NIPCe|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVvJR|UxRTF4LkeyO|Qh|ryP NYnpcVdCW0GQR1XS
RPMI-6666 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlrXTWM2OD1zNj65NlEyKM7:TR?= NVKzV2prW0GQR1XS
SIG-M5 NHLSTGhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYjJR|UxRTF5LkG5NFMh|ryP M1Psd3NCVkeHUh?=
VA-ES-BJ Ml\hS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYjW[pRiUUN3ME2xO{44PDVzIN88US=> MWnTRW5ITVJ?
MONO-MAC-6 NH;we4hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2nrTGlEPTB;MUeuPVMyOiEQvF2= M1TDN3NCVkeHUh?=
LAN-6 Mkf1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkLrTWM2OD1zOD63OVU4KM7:TR?= MVfTRW5ITVJ?
A388 NH7WZ3lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2Cxe2lEPTB;MUmuN|A2QSEQvF2= M3uzN3NCVkeHUh?=
SK-NEP-1 MoLPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIjaW|NKSzVyPUKwMlIyOzJizszN NEL5UVFUSU6JRWK=
TE-10 M1XZc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHG1SJNKSzVyPUKwMlUzOjFizszN MlfQV2FPT0WU
HL-60 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVXJR|UxRTJyLkmwPVkh|ryP NIXJVpVUSU6JRWK=
MC116 M{XZN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3\Y[2lEPTB;MkGuO|IzOSEQvF2= M{G4eXNCVkeHUh?=
SW962 MkHhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYPJR|UxRTJzLke5NVUh|ryP MWXTRW5ITVJ?
NOMO-1 M{LFPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXvQdJZTUUN3ME2yNk43PTZ2IN88US=> M4nMUHNCVkeHUh?=
CTB-1 M3r6d2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUXRZ2M6UUN3ME2yNk45PjdzIN88US=> NFHpWlZUSU6JRWK=
MRK-nu-1 Mk\HS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYC1V5hXUUN3ME2yNk46ODd2IN88US=> MlT2V2FPT0WU
GR-ST NV:xbJo6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWnJR|UxRTJ|Lke2JO69VQ>? Mn7ZV2FPT0WU
HH NUfOSm5FT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkTMTWM2OD1{ND6wNFMh|ryP M3ywbXNCVkeHUh?=
NCI-H1963 MkXXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHnPZppKSzVyPUK0MlA4QDJizszN MmnQV2FPT0WU
QIMR-WIL NEDBc4NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH3JbmxKSzVyPUK0Mlg4PzJizszN M3;ZdnNCVkeHUh?=
CGTH-W-1 NXHS[JNIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVLI[5BrUUN3ME2yOU4xPzJ|IN88US=> NHjTSXhUSU6JRWK=
LP-1 NYXFU|lJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{j2R2lEPTB;MkWuOlU2OSEQvF2= M1K1UXNCVkeHUh?=
NCI-H748 NXLyZ2ZGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWnJR|UxRTJ4LkWxN|ch|ryP MkTnV2FPT0WU
PF-382 MmruS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUnJR|UxRTJ5LkKyNlMh|ryP MWXTRW5ITVJ?
ATN-1 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHWxUpZKSzVyPUK3MlM4OzJizszN NEK1VnBUSU6JRWK=
L-540 MlzaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUD2N2dDUUN3ME2yO{43PDV7IN88US=> MkHUV2FPT0WU
LXF-289 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2TqTmlEPTB;MkeuO|UyQSEQvF2= M{LOSHNCVkeHUh?=
LS-513 MkHkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHjPR4VKSzVyPUK4MlE5ODdizszN NF25S3RUSU6JRWK=
NCI-H1581 Mn\zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX;heohsUUN3ME2zNE4{QTd4IN88US=> MlH2V2FPT0WU
ES6 NIPRfJZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4WwRmlEPTB;M{CuOlg6QSEQvF2= M1LafXNCVkeHUh?=
SW982 NGHIcnpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGjDdVFKSzVyPUOwMlg2PjZizszN MWnTRW5ITVJ?
DOHH-2 NFvjS41Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3PNfmlEPTB;M{GuOVg6OyEQvF2= NIrofYhUSU6JRWK=
DB NFeyTY1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2\qd2lEPTB;M{OuPVQ{OSEQvF2= NHj6VG5USU6JRWK=
MPP-89 NUTEUZhjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3T3dmlEPTB;M{SuNVc2PiEQvF2= Mnu2V2FPT0WU
LB831-BLC NESwWo5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWLJR|UxRTN2LkWxPFQh|ryP NVW0OHpVW0GQR1XS
NB5 NFPlbHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn;xTWM2OD1|ND64OVM2KM7:TR?= NWe3[nZSW0GQR1XS
GB-1 M1nNXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmDHTWM2OD1|NT6wOFY6KM7:TR?= MXvTRW5ITVJ?
TE-15 M33Wbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWjJR|UxRTN3LkKyN|gh|ryP MlLQV2FPT0WU
LC4-1 NY[3NmZkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoGzTWM2OD1|NT6zPFQ4KM7:TR?= MmLCV2FPT0WU
NCI-H747 M{XUemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHLsZpVKSzVyPUO2MlE{PjlizszN MmXiV2FPT0WU
NTERA-S-cl-D1 NVnXbGtVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2G3R2lEPTB;M{iuO|M1PyEQvF2= MUfTRW5ITVJ?
SK-MM-2 M1fBNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIDyd5hKSzVyPUSwMlEyPDZizszN MV3TRW5ITVJ?
TGW M1XiVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXTRcWVZUUN3ME20NU4xPTZ|IN88US=> MYLTRW5ITVJ?
ONS-76 M4TjVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGnWPFhKSzVyPUSyMlQ5QDNizszN MV;TRW5ITVJ?
CPC-N NVvWSG1CT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV[xN49OUUN3ME20Nk46QTdzIN88US=> NUH4N2w5W0GQR1XS
ES4 NX74eJAzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1mzTWlEPTB;NESuOFE2OyEQvF2= MYHTRW5ITVJ?
Daudi Ml3TS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV\JR|UxRTR3LkC4Nlch|ryP NVqwVVg6W0GQR1XS
MOLT-4 NHr1fG5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnjBTWM2OD12NT6wPFU{KM7:TR?= M{LZVHNCVkeHUh?=
HT-144 M{jRUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUTJR|UxRTR4LkeyOkDPxE1? NHvaR2xUSU6JRWK=
SW872 M{PBdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYG0SGltUUN3ME20PE4yQTN|IN88US=> NI\y[4pUSU6JRWK=
D-283MED NHnWSZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWTJR|UxRTR6LkO1OFIh|ryP Mlj5V2FPT0WU
NCI-H2126 MlfyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Moq1TWM2OD12OD64OFc3KM7:TR?= NV7vZ|FZW0GQR1XS
NCI-SNU-16 NWjmeVdtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUDJR|UxRTR7LkKxOFMh|ryP NIrrNJdUSU6JRWK=
CESS MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXvJR|UxRTR7LkWwPFgh|ryP NHmycXpUSU6JRWK=
A101D M1jTNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4q5fWlEPTB;NEmuPVc{PiEQvF2= Ml\rV2FPT0WU

... 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]

+ Expand

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]

+ Expand
  • 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]

+ Expand
  • 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

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03737994 Not yet recruiting ALK Gene Rearrangement|ALK Positive|Lung Non-Squamous Non-Small Cell Carcinoma|Stage IV Lung Cancer AJCC v8|Stage IVA Lung Cancer AJCC v8|Stage IVB Lung Cancer AJCC v8 National Cancer Institute (NCI) April 1 2019 Phase 2
NCT03737994 Not yet recruiting ALK Gene Rearrangement|ALK Positive|Lung Non-Squamous Non-Small Cell Carcinoma|Stage IV Lung Cancer AJCC v8|Stage IVA Lung Cancer AJCC v8|Stage IVB Lung Cancer AJCC v8 National Cancer Institute (NCI) April 1 2019 Phase 2
NCT03874273 Recruiting Inflammatory Myofibroblastic Tumor Federal Research Institute of Pediatric Hematology Oncology and Immunology February 1 2019 Phase 2|Phase 3
NCT03874273 Recruiting Inflammatory Myofibroblastic Tumor Federal Research Institute of Pediatric Hematology Oncology and Immunology February 1 2019 Phase 2|Phase 3
NCT03672643 Recruiting ALK-positive NSCLC Pfizer January 28 2019 Phase 4
NCT03672643 Recruiting ALK-positive NSCLC Pfizer January 28 2019 Phase 4

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

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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.

c-Met Signaling Pathway Map

c-Met Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID