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 129 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 MVLDfZRwfG:6aXOgRZN{[Xl? NGf3SG01QCCq MXHEUXNQ M1LtUWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KG2xdYPlJGJCTjNiY3XscJMh\XiycnXzd4lv\yCDTFugSlEyPzSOIH31eIFvfCClb3X4dJJme3OrbnegSW1NPCC5aYToJGlEPTBib3[gNE43OiEQvF2= NUXyZ3VROjF3N{K1PFk>
BAF3 MXjDfZRwfG:6aXOgRZN{[Xl? M2jIW|Q5KGh? NIHsVnpFVVOR M1POfmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KG2xdYPlJGJCTjNiY3XscJMh\XiycnXzd4lv\yCDTFugUFEyQT[PIH31eIFvfCClb3X4dJJme3OrbnegSW1NPCC5aYToJGlEPTBib3[gNk4zKM7:TR?= MV:yNVU4OjV6OR?=
BAF3 MonBR5l1d3SxeHnjJGF{e2G7 M{TXVlQ5KGh? MU\EUXNQ MVLDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRWY{KGOnbHzzJIV5eHKnc4PpcochTU2OND3BUGshf2m2aDDJR|UxKG:oIECuNlgh|ryP NGHUe4EzOTV5MkW4PS=>
Kelly NFTJfW9EgXSxdH;4bYMhSXO|YYm= M2nmbWROW09? NWn2WFRzS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hU2WubImgZ4VtdHNiZYjwdoV{e2mwZzDBUGshTjFzN{TMJI12fGGwdDD3bZRpKEmFNUCgc4YhOC52MjFOwG0> MnPjNlE2PzJ3OEm=
SH-SY5Y M3LDOGN6fG:2b4jpZ{BCe3OjeR?= NELXWWtFVVOR Ml\3R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV2guW1l3WTDj[YxteyCneIDy[ZN{cW6pIFHMT{BHOTF5NFygcZV1[W62IIfpeIghUUN3MDDv[kAxNjV|IN88US=> MmDLNlE2PzJ3OEm=
SMS-KCN NYTHZWRRS3m2b4TvfIlkKEG|c3H5 NUHhZohtTE2VTx?= MVjDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDTUXMuU0OQIHPlcIx{KGW6cILld5NqdmdiQVzLJHIyOjd3UTDteZRidnRid3n0bEBKSzVyIH;mJFAvQTFizszN NUPOfYNoOjF3N{K1PFk>
BAF3 NH\yTVJEgXSxdH;4bYMhSXO|YYm= Mn7TOFghcA>? NUC0Z|hmTE2VTx?= M1LXT2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KG2xdYPlJGJCTjNiY3XscJMh\XiycnXzd4lv\yCWZXytRWxMKHerdHigTWM2OCCxZjCwMlE6KM7:TR?= NInnSWQzOTV5MkW4PS=>
3T3 MUjGeY5kfGmxbjDBd5NigQ>? NYDVO3VpOSCq NH\IT5pFVVOR MWnJcohq[mm2aX;uJI9nKFKRTjDhd5Nme3OnZDDhd{Boem:5dHig[oFkfG:{LXnu[JVk\WRiYYX0c5Bpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOC5yODFOwG0> M2PYSVIyQDF{NEG0
3T3-E NV[1OpQyTnWwY4Tpc44hSXO|YYm= MkXVNUBp NFXaVIVFVVOR MXvJcohq[mm2aX;uJI9nKFSLRUKgZZN{\XO|ZXSg[5Jwf3SqIH\hZ5Rwei2rbnT1Z4VlKGG3dH;wbI9{eGixconsZZRqd25id3n0bEBKSzVyIH;mJFAvPDR6IN88US=> NXq4OFM4OjF6MUK0NVQ>
A549 M2rIS2tqdmG|ZTDBd5NigQ>? M2LQelEhcA>? MmDjSG1UVw>? M3rBXGlvcGmkaYTpc44hd2ZiaIXtZY4hemWlb33ibY5idnRiYz3NSXQhc2mwYYPlJIV5eHKnc4Pl[EBie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGhITi2rbnT1Z4VlKGG3dH;wbI9{eGixconsZZRqd25id3n0bEBKSzVyIH;mJFAvODB6IN88US=> NGTKZVYzOThzMkSxOC=>
BAF3-BCL NH3XVm9HfW6ldHnvckBCe3OjeR?= NEP4bFgyKGh? MVnEUXNQ MYLJcohq[mm2aX;uJI9nKEGETDDhd5Nme3OnZDDhd{Boem:5dHig[oFkfG:{LXnu[JVk\WRiYYX0c5Bpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOS5zNUmg{txO Mnr5NlE5OTJ2MUS=
HEK293 MYjGeY5kfGmxbjDBd5NigQ>? MUixJIg> MXjEUXNQ NVOxU4Y2UW6qaXLpeIlwdiCxZjDBXGwh[XO|ZYPz[YQh[XNiZ4Lve5RpKG[jY4Tvdk1qdmS3Y3XkJIF2fG:yaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIECuNlk1KM7:TR?= MYmyNVgyOjRzNB?=
HEK293 MYfGeY5kfGmxbjDBd5NigQ>? M3LzWFEhcA>? M4HCcWROW09? NHT6VYpKdmirYnn0bY9vKG:oIFnSJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iB{Lki4O{DPxE1? M1vmZVIyQDF{NEG0
Jurkat MXfGeY5kfGmxbjDBd5NigQ>? NGTUcGQyKGh? Mnj2SG1UVw>? NXjtUVREUW6qaXLpeIlwdiCxZjDMR2sh[XO|ZYPz[YQh[XNiZ4Lve5RpKG[jY4Tvdk1qdmS3Y3XkJIF2fG:yaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIEKuO|QyKM7:TR?= NF\ncVkzOThzMkSxOC=>
KARPAS299 MmTmT4lv[XOnIFHzd4F6 NF7T[WgyKGh? MX3EUXNQ NEXDUpNKdmirYnn0bY9vKG:oIFHMT{Bie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6wNkDPxE1? M3XX[lIyQDF{NEG0
PAE M4rST2Z2dmO2aX;uJGF{e2G7 NInqWlMyKGh? NV7XRVRqTE2VTx?= NI\E[25KdmirYnn0bY9vKG:oIGTST2Ih[XO|ZYPz[YQh[XNiZ4Lve5RpKG[jY4Tvdk1qdmS3Y3XkJIF2fG:yaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIECuN|k6KM7:TR?= NGTWXY4zOThzMkSxOC=>
BAF3 M4[1dmZ2dmO2aX;uJGF{e2G7 NFrHb2kzNTNiZB?= M3rZWWROW09? Mmn2TY5pcWKrdHnvckBw\iCWRVyt[pV{\WRiaX7zeYxqdiC{ZXPldJRweiCneIDy[ZN{\WRid3n0bEBKSzVyIH;mJFEvPjR|IN88US=> MVmyN|c1OjJ3Mh?=
KARPAS299 NIj1RXZEgXSxdH;4bYMhSXO|YYm= NEewblYzNTNiZB?= NX;0ZYx4TE2VTx?= MXrJR|UxRTBwME[0NkDPxE1? M3\3T|I{PzR{MkWy
EBC1 MnSxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIe4V4c4OiCq NEHFdXFFVVOR NFq5cY1KSzVyPUCuNFI{KM7:TR?= NUPxdI1xOjN7OUOzNlg>
HCT116 NFm3W4lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYG3NkBp Mni1SG1UVw>? MWjJR|UxRTF2LkiyJO69VQ>? NHWyXHMzOzl7M{OyPC=>
MCF7 NVfjNGk6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX\xe3lEPzJiaB?= MWPEUXNQ MWPJR|UxRTlwNUig{txO M{K5WVI{QTl|M{K4
MDA-MB-231 M2LLXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIHGT3M4OiCq NETldoJFVVOR NW\qWHE5UUN3ME2xNE45KM7:TR?= NUK5UW9UOjN7OUOzNlg>
MKN45 M1fRe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M162d|czKGh? MVvEUXNQ Mke3TWM2OD1yLkCxN{DPxE1? MVGyN|k6OzN{OB?=
NCI-H441 MnXpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4DjSlczKGh? M1jLVGROW09? NYTFNWhEUUN3ME2xO{4zPSEQvF2= MWCyN|k6OzN{OB?=
NCI-H661 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4HRZ|czKGh? NHnqS3VFVVOR NEXqVVVKSzVyPUGxMlQ4KM7:TR?= MXyyN|k6OzN{OB?=
SK-MEL-28 NVjyZZMzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIP1Nm44OiCq MU\EUXNQ MXjJR|UxRTFyLkm3JO69VQ>? MnnsNlM6QTN|Mki=
SKOV3 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIHqUmQ4OiCq NYXUPYRuTE2VTx?= MYjJR|UxRTF{Lki1JO69VQ>? MXeyN|k6OzN{OB?=
SNU5 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIrNVVQ4OiCq MXHEUXNQ M1HmVWlEPTB;MD6wNVYh|ryP NVPZNndwOjN7OUOzNlg>
NCI-H2228 NEfjdllIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXGzZ49TPzJiaB?= NVXLXYYzTE2VTx?= M{f0bWlvcGmkaYTpc44hd2ZiQVzLMYZ2e2mxbjDkdol3\W5iY3XscEBxem:uaX\ldoF1cW:wIIfpeIghUUN3MDDv[kAxNjFzODFOwG0> MoSzNlQ1OzJ7MEm=
NCI-H3122 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVO3NkBp NEfifHlFVVOR M4DsXWlvcGmkaYTpc44hd2ZiQVzLMYZ2e2mxbjDkdol3\W5iY3XscEBxem:uaX\ldoF1cW:wIIfpeIghUUN3MDDv[kAxNjFyODFOwG0> MUmyOFQ{OjlyOR?=
NCI-H3122 Ml72S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mlz5O|IhcA>? NFHINIhFVVOR NFTHN2xKdmirYnn0bY9vKG:oIFHMT{1nfXOrb36g[JJqfmWwIHPlcIwheHKxbHnm[ZJifGmxbjDpckBpfW2jbjDOR2kuUDNzMkKgZ4VtdHNiaHHyZo9zcW6pIFHMT{BIOTJ4OVGgcZV1[W62IIfpeIghUUN3MDDv[kAxNjZ{MzFOwG0> NVfN[FlxOjR2M{K5NFk>
NCI-H3122 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmLqO|IhcA>? M3npV2ROW09? MYTJcohq[mm2aX;uJI9nKEGOSz3meZNqd25iZILpeoVvKGOnbHygdJJwdGmoZYLheIlwdiCrbjDoeY1idiCQQ1mtTFMyOjJiY3XscJMhcGG{Yn;ybY5oKEGOSzDMNVE6Pk1ibYX0ZY51KHerdHigTWM2OCCxZjCwMlg{QCEQvF2= MnrjNlQ1OzJ7MEm=
NIH-3T3 NY\vVY1qU2mwYYPlJGF{e2G7 MkXMNUBp NIC4UVRFVVOR NGfqPHhKdmirYnn0bY9vKG:oIHj1cYFvKHerbHSgeJlx\SCHTVy0MYZ2e2WmIFHMT{BmgHC{ZYPz[YQh[XO|ZYPz[YQh[XNicHjvd5Bpd3K7bHH0[YQhSUyNIHzleoVtKHerdHigTWM2OCCxZjCwMlA5KM7:TR?= MX:yOFQ{OjlyOR?=
NIH-3T3 NXu1N|BMU2mwYYPlJGF{e2G7 NXPJTJJqOSCq NWfFb4RpTE2VTx?= M2nyTWlvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugS|EzPjmDIH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDBwNkC1JO69VQ>? MXyyOFQ{OjlyOR?=
NIH-3T3 M3u4OWtqdmG|ZTDBd5NigQ>? M33DdVEhcA>? Mn7nSG1UVw>? NFTsbGFKdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJHMyOjB4WTDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLk[yOkDPxE1? MVOyOFQ{OjlyOR?=
NIH-3T3 MX3LbY5ie2ViQYPzZZk> NE\KXFQyKGh? MnvGSG1UVw>? MnnYTY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzDMNVE6Pk1ibYX0ZY51KGW6cILld5Nm\CCjc4Pld5Nm\CCjczDwbI9{eGixLVHMT{Bt\X[nbDD3bZRpKEmFNUCgc4YhOC56NEOg{txO M2DwNFI1PDN{OUC5
NIH-3T3 MXPLbY5ie2ViQYPzZZk> NVP1WGs5OSCq MXfEUXNQ M{P2NWlvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugUFEyPTKUIH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDFwMEK2JO69VQ>? MXGyOFQ{OjlyOR?=
BAF3 MomzSpVv[3Srb36gRZN{[Xl? M1jKclczKGh? NIrkemFFVVOR NW\xR4d{UW6qaXLpeIlwdiCxZjDOVG0wSUyNIITyZY5{\mWldHXkJIF{e2W|c3XkJIF{KGOnbHyg[5Jwf3SqIHnubIljcXSrb36ge4l1cCCLQ{WwJI9nKDBwMEWxJO69VQ>? M1vUUFI1PDZ6NkOy
BAF3 MoDHR5l1d3SxeHnjJGF{e2G7 MY[3NkBp M{TV[GROW09? MYPJR|UxRTBwOUig{txO NWXNbodoOjR2Nki2N|I>
NIH-3T3 M{HaNGtqdmG|ZTDBd5NigQ>? MojGNUBp MXrJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIF[xNVc1VCCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAxNjF4NTFOwG0> MnzJNlQ5OTlzMU[=
NIH-3T3 NFLw[mtMcW6jc3WgRZN{[Xl? NHzOWXAyKGh? NGDlWHpKdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJGMyOTV4WTDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLkS3PEDPxE1? NXX5eXhLOjR6MUmxNVY>
NIH-3T3 NUPBVnBmU2mwYYPlJGF{e2G7 MUKxJIg> MXvJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIFexNlAzWiCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAyNjF2ODFOwG0> M4HKS|I1QDF7MUG2
NIH-3T3 MXXLbY5ie2ViQYPzZZk> M{TselEhcA>? M4\sR2lvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugNVE2OVSrboOgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMz6wN|kh|ryP MXyyOFgyQTFzNh?=
KARPAS299 MkPKT4lv[XOnIFHzd4F6 M4PTUVkxKG2rbh?= NF\MOZZFVVOR NFrjW|lKdmirYnn0bY9vKG:oIF7QUU1nfXOnZDDBUGsheGixc4Doc5J6dGG2aX;uJIV5eHKnc4Pl[EB4cXSqIFnDOVAhd2ZiMD6xNUDPxE1? MoHnNlQ6ODB5NUC=
MKN 45 NXvnZ491U2mwYYPlJGF{e2G7 NHz4O4gyKGh? NWT6eZhNTE2VTx?= M33UTmlvcGmkaYTpc44hd2ZiYz3N[ZQheGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iByLkCyJO69VQ>? MV6yOFkxODd3MB?=
A549 MmDSR5l1d3SxeHnjJGF{e2G7 NF\FZ2s1QCCq Mlf5SG1UVw>? MVTJR|UxKG:oIESuNFg1KM7:TR?= M4X2PFI1QTByOEOw
NCI-H1975 MVjDfZRwfG:6aXOgRZN{[Xl? Ml24OFghcA>? M3\zTWROW09? Mlj1TWM2OCCxZjC3MlU2OSEQvF2= MViyOFkxODh|MB?=
NCI-H1993 NELJWXNEgXSxdH;4bYMhSXO|YYm= NYDZR5RzPDhiaB?= M1\md2ROW09? M1HkSWlEPTBib3[gNE4xPjFizszN NXvtWmRjOjR7MEC4N|A>
NCI-H1993 M1nPPGFxd3Sxc3nzJGF{e2G7 MWmxJO69VQ>? MUiyOEBp NXjSfYVlTE2VTx?= MXPkc4V{KG6xdDDpcoR2[2ViYYDvdJRwe2m| NYXRO|JGOjR7MEC4N|A>
NIH-3T3 M1vyZWN6fG:2b4jpZ{BCe3OjeR?= NY\iWJdKPDhiaB?= MlfiSG1UVw>? NIr3eIlKSzVyIH;mJFAvOzZ2IN88US=> MVeyOFkxODh|MB?=
EBC1 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnzCO|IhcA>? NWi5dG5[TE2VTx?= MWnJR|UxKG:oIECuNFA3QSEQvF2= MV:yOFkxODh|MR?=
KARPAS299 MmPrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{\I[|czKGh? NX;VO4VWTE2VTx?= NG[4eZlKSzVyIH;mJFAvOiEQvF2= M{Lx[FI1QTByOEOx
NB1 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHewV2JKSzVyPUmxMlk5KG6P Mnz0V2FPT0WU
NCI-SNU-5 NInvfHNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXHJR|UxRTFyNT63OUBvVQ>? MnvvV2FPT0WU
SR MoWwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFqxZmZKSzVyPUGyOk4{OSCwTR?= NX\4NI9TW0GQR1XS
SF539 NULNU|J5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MU\JR|UxRTJyND6yOEBvVQ>? MoXNV2FPT0WU
SU-DHL-1 NU\EXY9GT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF\MVllKSzVyPUOzOk45OiCwTR?= MmHpV2FPT0WU
SCC-3 NGjYNmlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUDJR|UxRTN3Nj63OkBvVQ>? NVTac3VEW0GQR1XS
DEL MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmfxTWM2OD1|NkmuPUBvVQ>? MVzTRW5ITVJ?
CTV-1 NVPoWmdZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmjTTWM2OD13OU[uOFghdk1? NWHJU3UyW0GQR1XS
EM-2 NID3e2hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2W3dWlEPTB;NkCxMlM1KG6P NILzOI1USU6JRWK=
MHH-CALL-2 M3nMNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkfaTWM2OD14OEKuOVchdk1? NGq2dGhUSU6JRWK=
KM12 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX\wSIlZUUN3ME23NFYvQSCwTR?= NUH3eoRFW0GQR1XS
KINGS-1 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M37PNWlEPTB;N{S5Mlc2KG6P NFLpbYlUSU6JRWK=
MEG-01 MoLzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXPaNm1UUUN3ME24OVcvPjZibl2= NIrWN3hUSU6JRWK=
BV-173 M2rSVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NE[wWmxKSzVyPUGuNFU6QTdizszN M3jRenNCVkeHUh?=
LAMA-84 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2j0VWlEPTB;MT6zPFI5OiEQvF2= M2S1Z3NCVkeHUh?=
KARPAS-299 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYPafngyUUN3ME2xMlQxQDZzIN88US=> M1S2WXNCVkeHUh?=
K-562 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUXlS4lkUUN3ME2xMlczOjZ7IN88US=> MluxV2FPT0WU
SK-LMS-1 NXq5fnRRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFnmcVFKSzVyPUGuO|Y5PjdizszN NF;LZo5USU6JRWK=
MOLT-16 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlrwTWM2OD1zLkm1OVc2KM7:TR?= NIC2Z4xUSU6JRWK=
CMK NF;TNItIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWrQV2NtUUN3ME2xMlk3OTV7IN88US=> M33vWHNCVkeHUh?=
ST486 NYD1Wm5oT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFnYUYNKSzVyPUKuOFMxPzNizszN MX\TRW5ITVJ?
CI-1 NYLpNXY4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIHD[IlKSzVyPUKuOFk3PTlizszN NX7wdZhxW0GQR1XS
KP-N-RT-BM-1 NX\lfIhtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWTJR|UxRTJwN{CxNlIh|ryP MUjTRW5ITVJ?
ALL-PO NHe3eoFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWXJR|UxRTNwMUiyNFch|ryP NY\HVZJFW0GQR1XS
KS-1 M1HCO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVXJR|UxRTNwMkGyNlUh|ryP MUDTRW5ITVJ?
Becker MlXRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHjmSmxKSzVyPUSuNlM6OyEQvF2= MlfsV2FPT0WU
GDM-1 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWTJR|UxRTRwMkS2NVch|ryP MmDGV2FPT0WU
BC-1 M{XDfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnX3TWM2OD12LkS5Nlc4KM7:TR?= MXLTRW5ITVJ?
NB14 NV\LdYxWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3jDfmlEPTB;ND64N|UzPCEQvF2= M3jLdHNCVkeHUh?=
NOS-1 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkjkTWM2OD13LkOzPFc1KM7:TR?= MWrTRW5ITVJ?
MZ1-PC MoC2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVXqV5Y5UUN3ME21MlgzOTVzIN88US=> M4LUW3NCVkeHUh?=
A498 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVLJR|UxRTZwMEi0O|Mh|ryP NXLMbodiW0GQR1XS
EW-16 NUDkboY1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3[5O2lEPTB;Nj6zO|c4OyEQvF2= MnjYV2FPT0WU
NALM-6 M13ROmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF;qT5hKSzVyPU[uOlg{QDdizszN NV\yN2xPW0GQR1XS
EB-3 NHfwcG5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkHiTWM2OD15LkC3NlM{KM7:TR?= MmLnV2FPT0WU
697 M{XEWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH7nSWpKSzVyPUmuNlQ{OjlizszN MVPTRW5ITVJ?
Ramos-2G6-4C10 NEfQZW9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGXkUIxKSzVyPUmuOVk5PDJizszN NHfMSGhUSU6JRWK=
KNS-81-FD NX3lcmdrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX;JR|UxRTlwNkm2OVMh|ryP MmLSV2FPT0WU
HUTU-80 NV\adIpNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYXTc5pUUUN3ME25Mlc1PjR{IN88US=> MUjTRW5ITVJ?
LS-411N M13YRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{DUe2lEPTB;MUCuNFU3PyEQvF2= MYPTRW5ITVJ?
RPMI-8402 NITiV4JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1y3VWlEPTB;MUCuNVE3KM7:TR?= NWLlSFRkW0GQR1XS
KU812 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH3ETYRKSzVyPUGwMlI6QTFizszN MUnTRW5ITVJ?
EW-1 NWLOZmlHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NG[2OFVKSzVyPUGwMlQ1OjVizszN NVrQd3JXW0GQR1XS
HC-1 NWW2[odLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXPJR|UxRTFyLkS4OFQh|ryP M3HUV3NCVkeHUh?=
NB69 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlLlTWM2OD1zMD61NFQ{KM7:TR?= NEewRnpUSU6JRWK=
MFH-ino NWf5SlZzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUfxZWRoUUN3ME2xNE45OzB|IN88US=> M3jBRnNCVkeHUh?=
CCRF-CEM NE\lZVZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEPXb|FKSzVyPUGxMlU6PyEQvF2= M2S3Z3NCVkeHUh?=
SK-N-DZ MmT3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXHhUHQxUUN3ME2xNk4xPDN4IN88US=> NWfRd2FsW0GQR1XS
NCI-H720 NGP4S3BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{LVemlEPTB;MUKuNVcxPSEQvF2= MX\TRW5ITVJ?
HCC1187 MnruS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXfJR|UxRTF{LkKwOFEh|ryP NYPLXlZtW0GQR1XS
IST-SL2 M1;IcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{[3NmlEPTB;MUKuOFg4OiEQvF2= Mo\4V2FPT0WU
KE-37 M1\OZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnHRTWM2OD1zMj63PVY3KM7:TR?= NFvQeVVUSU6JRWK=
HCC1599 Mn\DS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1PKcGlEPTB;MUKuPVA3QSEQvF2= MkPPV2FPT0WU
A4-Fuk MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH\CTWZKSzVyPUGyMlk2QDZizszN MUHTRW5ITVJ?
NKM-1 NILDRYRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlzHTWM2OD1zMz6yPVI2KM7:TR?= NIPQSGFUSU6JRWK=
BE-13 M331ZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NELvW2lKSzVyPUGzMlc6QDlizszN MknDV2FPT0WU
MV-4-11 M2HWeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHHlVWhKSzVyPUG0MlA{OjRizszN NYTISYVuW0GQR1XS
OPM-2 MnW2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkiyTWM2OD1zND60NFg2KM7:TR?= NGrH[ZZUSU6JRWK=
KARPAS-422 NHzvUohIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVrJR|UxRTF2LkWxNlYh|ryP NHuwfGhUSU6JRWK=
RPMI-8226 NHHubo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIeyN5JKSzVyPUG0Mlg6OTVizszN NVXVe4E4W0GQR1XS
KARPAS-45 MlTFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVnJR|UxRTF3Lke3NVYh|ryP NVrTRZM{W0GQR1XS
SK-PN-DW NGPYe5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MknQTWM2OD1zNT64OlMyKM7:TR?= MXnTRW5ITVJ?
LC-2 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUjOPXN{UUN3ME2xOk4yPTB4IN88US=> M13H[nNCVkeHUh?=
NCI-H1648 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1niXGlEPTB;MU[uNlU1KM7:TR?= NUPIU2h5W0GQR1XS
RL95-2 M37U[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1yydWlEPTB;MU[uN|k4QCEQvF2= NW\lXmJLW0GQR1XS
KNS-42 Ml33S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGHhOXVKSzVyPUG2MlczPzRizszN MmTkV2FPT0WU
RPMI-6666 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mkm2TWM2OD1zNj65NlEyKM7:TR?= MUDTRW5ITVJ?
SIG-M5 NIfHOmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYO2XmxMUUN3ME2xO{4yQTB|IN88US=> NFv2WoFUSU6JRWK=
VA-ES-BJ M{nsemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGHCOY1KSzVyPUG3Mlc1PTFizszN M3LnOnNCVkeHUh?=
MONO-MAC-6 NVj2dItwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVHJR|UxRTF5LkmzNVIh|ryP M4fLS3NCVkeHUh?=
LAN-6 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2S0TWlEPTB;MUiuO|U2PyEQvF2= M1LJfXNCVkeHUh?=
A388 MkHUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUDJR|UxRTF7LkOwOVkh|ryP NGnZb5FUSU6JRWK=
SK-NEP-1 NWjwWnNnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mo\hTWM2OD1{MD6yNVMzKM7:TR?= NFrhb49USU6JRWK=
TE-10 NGLvZVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlfzTWM2OD1{MD61NlIyKM7:TR?= NEjNZoVUSU6JRWK=
HL-60 M33JWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M33SVGlEPTB;MkCuPVA6QSEQvF2= MXfTRW5ITVJ?
MC116 NHHtTWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWLJR|UxRTJzLkeyNlEh|ryP NEnNXY1USU6JRWK=
SW962 M1zIWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF;xR2FKSzVyPUKxMlc6OTVizszN NGeyeWdUSU6JRWK=
NOMO-1 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFPlXnhKSzVyPUKyMlY2PjRizszN NHnYe5VUSU6JRWK=
CTB-1 NIfmS5pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXTJR|UxRTJ{Lki2O|Eh|ryP NH;GWpZUSU6JRWK=
MRK-nu-1 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXPJR|UxRTJ{LkmwO|Qh|ryP MU\TRW5ITVJ?
GR-ST M{PvN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2nOR2lEPTB;MkOuO|Yh|ryP NYDwd2N4W0GQR1XS
HH MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1:5bGlEPTB;MkSuNFA{KM7:TR?= NUDQRXRpW0GQR1XS
NCI-H1963 Mn:yS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYjmUll4UUN3ME2yOE4xPzh{IN88US=> MmHIV2FPT0WU
QIMR-WIL M4XE[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{XzNWlEPTB;MkSuPFc4OiEQvF2= M1TRUnNCVkeHUh?=
CGTH-W-1 MkPxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1XqOmlEPTB;MkWuNFczOyEQvF2= NWfRXoxtW0GQR1XS
LP-1 NGrrNI1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYPJR|UxRTJ3Lk[1OVEh|ryP NFHMN2xUSU6JRWK=
NCI-H748 NFTvNlFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFXLdGRKSzVyPUK2MlUyOzdizszN M1PmUnNCVkeHUh?=
PF-382 MkflS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF7Wd4FKSzVyPUK3MlIzOjNizszN M3i5N3NCVkeHUh?=
ATN-1 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MojxTWM2OD1{Nz6zO|MzKM7:TR?= M{fxfXNCVkeHUh?=
L-540 NUf3PVFST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnG4TWM2OD1{Nz62OFU6KM7:TR?= MoTUV2FPT0WU
LXF-289 Ml3KS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVXQO2hJUUN3ME2yO{44PTF7IN88US=> M{HGVXNCVkeHUh?=
LS-513 M{fxPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWPV[mVNUUN3ME2yPE4yQDB5IN88US=> MWLTRW5ITVJ?
NCI-H1581 MljSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUnJR|UxRTNyLkO5O|Yh|ryP NFvDSlFUSU6JRWK=
ES6 NHTFcnZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1;kV2lEPTB;M{CuOlg6QSEQvF2= MYrTRW5ITVJ?
SW982 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWTJR|UxRTNyLki1OlYh|ryP NFTIfW9USU6JRWK=
DOHH-2 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4m0OGlEPTB;M{GuOVg6OyEQvF2= MYDTRW5ITVJ?
DB NXrRW5ZwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkfrTWM2OD1|Mz65OFMyKM7:TR?= MWLTRW5ITVJ?
MPP-89 M2DndGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoTlTWM2OD1|ND6xO|U3KM7:TR?= MXLTRW5ITVJ?
LB831-BLC NHvBc4hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEiwR4JKSzVyPUO0MlUyQDRizszN MXfTRW5ITVJ?
NB5 MkG0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX\JR|UxRTN2Lki1N|Uh|ryP NUPs[GdKW0GQR1XS
GB-1 NUPIPIppT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVPJR|UxRTN3LkC0Olkh|ryP Mkf2V2FPT0WU
TE-15 M4DyWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXPJR|UxRTN3LkKyN|gh|ryP M2ThVnNCVkeHUh?=
LC4-1 NF:1UIJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkDWTWM2OD1|NT6zPFQ4KM7:TR?= M{nNRXNCVkeHUh?=
NCI-H747 NFvlcFVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MULJR|UxRTN4LkGzOlkh|ryP NFO0[m5USU6JRWK=
NTERA-S-cl-D1 M2Lrbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mny5TWM2OD1|OD63N|Q4KM7:TR?= MWLTRW5ITVJ?
SK-MM-2 NEjsXndIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUTselNZUUN3ME20NE4yOTR4IN88US=> MVXTRW5ITVJ?
TGW NF3UeG5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUPJR|UxRTRzLkC1OlMh|ryP NYLGR|l4W0GQR1XS
ONS-76 MlTDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnXyTWM2OD12Mj60PFg{KM7:TR?= M4\NVHNCVkeHUh?=
CPC-N M4nYT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXTJR|UxRTR{Lkm5O|Eh|ryP M{jjXXNCVkeHUh?=
ES4 NITVT|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M17KSWlEPTB;NESuOFE2OyEQvF2= MY\TRW5ITVJ?
Daudi M4rRRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2Pu[GlEPTB;NEWuNFgzPyEQvF2= M1\lbnNCVkeHUh?=
MOLT-4 NEL2eXhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFjTTHBKSzVyPUS1MlA5PTNizszN NF\qUWpUSU6JRWK=
HT-144 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXHJR|UxRTR4LkeyOkDPxE1? M2DrcHNCVkeHUh?=
SW872 NUXw[GRET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXzJR|UxRTR6LkG5N|Mh|ryP MkLKV2FPT0WU
D-283MED NH2y[HNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2r2WGlEPTB;NEiuN|U1OiEQvF2= M1HGbHNCVkeHUh?=
NCI-H2126 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXjJR|UxRTR6Lki0O|Yh|ryP NVH2U21KW0GQR1XS
NCI-SNU-16 Mn\hS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoPuTWM2OD12OT6yNVQ{KM7:TR?= M3jPZ3NCVkeHUh?=
CESS M1T0S2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH7I[mVKSzVyPUS5MlUxQDhizszN NUnrXnJ2W0GQR1XS
A101D MkXNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUHJR|UxRTR7Lkm3N|Yh|ryP NXHzd2MzW0GQR1XS

... 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 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