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 226 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 NYr6R25lS3m2b4TvfIlkKEG|c3H5 NYTkTVVCPDhiaB?= M4jEcmROW09? NVXlOINkS3m2b4TvfIlkcXS7IHHnZYlve3RibX;1d4UhSkGIMzDj[YxteyCneIDy[ZN{cW6pIFHMT{BHOTF5NFygcZV1[W62IHPv[ZhxemW|c3nu[{BGVUx2IIfpeIghUUN3MDDv[kAxNjZ{IN88US=> NHfYVZozOTV5MkW4PS=>
BAF3 NFPF[plEgXSxdH;4bYMhSXO|YYm= NEPXUIk1QCCq MVfEUXNQ MYXDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRWY{KGOnbHzzJIV5eHKnc4PpcochSUyNIFyxNVk3VSCvdYThcpQh[2:neIDy[ZN{cW6pIFXNUFQhf2m2aDDJR|UxKG:oIEKuNkDPxE1? NH\XfmkzOTV5MkW4PS=>
BAF3 MXvDfZRwfG:6aXOgRZN{[Xl? MlTjOFghcA>? NI\3SphFVVOR NH;Td4pEgXSxdH;4bYNqfHliYXfhbY5{fCCvb4Xz[UBDSUZ|IHPlcIx{KGW6cILld5NqdmdiRV3MOE1CVEtid3n0bEBKSzVyIH;mJFAvOjhizszN M4T6OFIyPTd{NUi5
Kelly M2\TSWN6fG:2b4jpZ{BCe3OjeR?= MYfEUXNQ M1jnNmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGtmdGy7IHPlcIx{KGW6cILld5NqdmdiQVzLJGYyOTd2TDDteZRidnRid3n0bEBKSzVyIH;mJFAvPDJizszN NXv6XXk5OjF3N{K1PFk>
SH-SY5Y MnjnR5l1d3SxeHnjJGF{e2G7 M4juSmROW09? NX;2THptS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hW0hvU2m1XUBk\WyuczDlfJBz\XO|aX7nJGFNUyCIMUG3OGwhdXW2YX70JJdqfGhiSVO1NEBw\iByLkWzJO69VQ>? M4XjRVIyPTd{NUi5
SMS-KCN M4jJSWN6fG:2b4jpZ{BCe3OjeR?= NUXtXms6TE2VTx?= Ml;LR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV21UNUuFTjDj[YxteyCneIDy[ZN{cW6pIFHMT{BTOTJ5NWGgcZV1[W62IIfpeIghUUN3MDDv[kAxNjlzIN88US=> M{HBNFIyPTd{NUi5
BAF3 NIfBVXREgXSxdH;4bYMhSXO|YYm= MkC0OFghcA>? MmTZSG1UVw>? M1yxcmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KG2xdYPlJGJCTjNiY3XscJMh\XiycnXzd4lv\yCWZXytRWxMKHerdHigTWM2OCCxZjCwMlE6KM7:TR?= MYOyNVU4OjV6OR?=
3T3 MWrGeY5kfGmxbjDBd5NigQ>? NIW3VYMyKGh? MkXLSG1UVw>? M1qyT2lvcGmkaYTpc44hd2ZiUl;OJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iByLkC4JO69VQ>? M2XzclIyQDF{NEG0
3T3-E NYm3R2JXTnWwY4Tpc44hSXO|YYm= MUWxJIg> MmDrSG1UVw>? NUL6blUxUW6qaXLpeIlwdiCxZjDUTWUzKGG|c3Xzd4VlKGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iByLkS0PEDPxE1? M13Ve|IyQDF{NEG0
A549 MkDIT4lv[XOnIFHzd4F6 NWLhUJZrOSCq NXTi[XhnTE2VTx?= NFTGSmtKdmirYnn0bY9vKG:oIHj1cYFvKHKnY3;tZolv[W62IHOtUWVVKGurbnHz[UBmgHC{ZYPz[YQh[XO|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBJT0ZvaX7keYNm\CCjdYTvdIhwe3Cqb4L5cIF1cW:wIIfpeIghUUN3MDDv[kAxNjByODFOwG0> M2DUVVIyQDF{NEG0
BAF3-BCL NWKzVY82TnWwY4Tpc44hSXO|YYm= NXPpTnpHOSCq NVP0VmZlTE2VTx?= MoHjTY5pcWKrdHnvckBw\iCDQlygZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDFwMUW5JO69VQ>? MUOyNVgyOjRzNB?=
HEK293 NInOXWZHfW6ldHnvckBCe3OjeR?= NX7wd29zOSCq NVTySnhVTE2VTx?= NFnrNmdKdmirYnn0bY9vKG:oIFHYUEBie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6yPVQh|ryP MVyyNVgyOjRzNB?=
HEK293 MkjtSpVv[3Srb36gRZN{[Xl? M13IOVEhcA>? MortSG1UVw>? MlvOTY5pcWKrdHnvckBw\iCLUjDhd5Nme3OnZDDhd{Boem:5dHig[oFkfG:{LXnu[JVk\WRiYYX0c5Bpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOi56OEeg{txO M{\hcVIyQDF{NEG0
Jurkat NHnTUWVHfW6ldHnvckBCe3OjeR?= M1jQ[FEhcA>? MUDEUXNQ MWTJcohq[mm2aX;uJI9nKEyFSzDhd5Nme3OnZDDhd{Boem:5dHig[oFkfG:{LXnu[JVk\WRiYYX0c5Bpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOi55NEGg{txO MmDVNlE5OTJ2MUS=
KARPAS299 MVfLbY5ie2ViQYPzZZk> MmPYNUBp MXzEUXNQ NIHOSndKdmirYnn0bY9vKG:oIFHMT{Bie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6wNkDPxE1? NXX5NWVPOjF6MUK0NVQ>
PAE MX;GeY5kfGmxbjDBd5NigQ>? M4T1dVEhcA>? MnHESG1UVw>? NHL6UIlKdmirYnn0bY9vKG:oIGTST2Ih[XO|ZYPz[YQh[XNiZ4Lve5RpKG[jY4Tvdk1qdmS3Y3XkJIF2fG:yaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIECuN|k6KM7:TR?= MXiyNVgyOjRzNB?=
BAF3 MYrGeY5kfGmxbjDBd5NigQ>? MmT6Nk0{KGR? M3TB[2ROW09? M1WwPWlvcGmkaYTpc44hd2ZiVFXMMYZ2e2WmIHnud5VtcW5icnXj[ZB1d3JiZYjwdoV{e2WmIIfpeIghUUN3MDDv[kAyNjZ2MzFOwG0> M2HKOlI{PzR{MkWy
KARPAS299 M2HDOWN6fG:2b4jpZ{BCe3OjeR?= MnrWNk0{KGR? MUjEUXNQ NVviTXVwUUN3ME2wMlA3PDJizszN MkiwNlM4PDJ{NUK=
EBC1 Ml3MS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYrKe4NWPzJiaB?= M1riZmROW09? M2i0SGlEPTB;MD6wNlMh|ryP MUCyN|k6OzN{OB?=
HCT116 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NE\YXnM4OiCq MnrwSG1UVw>? MVnJR|UxRTF2LkiyJO69VQ>? Mn\iNlM6QTN|Mki=
MCF7 NH\3b4lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4HBOFczKGh? NF65bIxFVVOR Mom4TWM2OD17LkW4JO69VQ>? MVGyN|k6OzN{OB?=
MDA-MB-231 NX3FdpF2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGrVVFk4OiCq MoP0SG1UVw>? NWPRcmJOUUN3ME2xNE45KM7:TR?= NVTRUYd4OjN7OUOzNlg>
MKN45 Mlq5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV[3NkBp NIi2Z5VFVVOR MUjJR|UxRTBwMEGzJO69VQ>? MXmyN|k6OzN{OB?=
NCI-H441 NVTJNVkxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXG3NkBp MoPvSG1UVw>? NETm[IFKSzVyPUG3MlI2KM7:TR?= NU\MSmRFOjN7OUOzNlg>
NCI-H661 NYHtO41xT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYK3NkBp M1vieGROW09? MWTJR|UxRTFzLkS3JO69VQ>? Ml;5NlM6QTN|Mki=
SK-MEL-28 M2TCTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlyxO|IhcA>? M4nRfWROW09? MV7JR|UxRTFyLkm3JO69VQ>? M{\NSVI{QTl|M{K4
SKOV3 NGHKV2ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWW3NkBp M17EV2ROW09? NFXTNpNKSzVyPUGyMlg2KM7:TR?= NEXSV3czOzl7M{OyPC=>
SNU5 NWXoUmlET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXnpNYFmPzJiaB?= MVPEUXNQ MWDJR|UxRTBwMEG2JO69VQ>? M{nHR|I{QTl|M{K4
NCI-H2228 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHHwNFM4OiCq M37XOGROW09? M2LhdGlvcGmkaYTpc44hd2ZiQVzLMYZ2e2mxbjDkdol3\W5iY3XscEBxem:uaX\ldoF1cW:wIIfpeIghUUN3MDDv[kAxNjFzODFOwG0> MWCyOFQ{OjlyOR?=
NCI-H3122 MkLuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2nP[|czKGh? Mn\ESG1UVw>? NHrkSGlKdmirYnn0bY9vKG:oIFHMT{1nfXOrb36g[JJqfmWwIHPlcIwheHKxbHnm[ZJifGmxbjD3bZRpKEmFNUCgc4YhOC5zMEig{txO M1zjdVI1PDN{OUC5
NCI-H3122 NUC2[|B4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVG3NkBp NYTBflJRTE2VTx?= M3\SfmlvcGmkaYTpc44hd2ZiQVzLMYZ2e2mxbjDkdol3\W5iY3XscEBxem:uaX\ldoF1cW:wIHnuJIh2dWGwIF7DTU1JOzF{MjDj[YxteyCqYYLic5JqdmdiQVzLJGcyOjZ7QTDteZRidnRid3n0bEBKSzVyIH;mJFAvPjJ|IN88US=> NGDPcZczPDR|MkmwPS=>
NCI-H3122 NXjKfoQ6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{XVWlczKGh? NXOwZmJZTE2VTx?= MVLJcohq[mm2aX;uJI9nKEGOSz3meZNqd25iZILpeoVvKGOnbHygdJJwdGmoZYLheIlwdiCrbjDoeY1idiCQQ1mtTFMyOjJiY3XscJMhcGG{Yn;ybY5oKEGOSzDMNVE6Pk1ibYX0ZY51KHerdHigTWM2OCCxZjCwMlg{QCEQvF2= Mk\hNlQ1OzJ7MEm=
NIH-3T3 NH7zVItMcW6jc3WgRZN{[Xl? M1vkSlEhcA>? NF7wU49FVVOR M{Tn[mlvcGmkaYTpc44hd2ZiaIXtZY4hf2muZDD0fZBmKEWPTESt[pV{\WRiQVzLJIV5eHKnc4Pl[EBie3Onc4Pl[EBieyCyaH;zdIhwenmuYYTl[EBCVEtibHX2[Ywhf2m2aDDJR|UxKG:oIECuNFgh|ryP NF;wUVAzPDR|MkmwPS=>
NIH-3T3 M4[0NmtqdmG|ZTDBd5NigQ>? M12wRlEhcA>? MofOSG1UVw>? M3TGV2lvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugS|EzPjmDIH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDBwNkC1JO69VQ>? M4\S[VI1PDN{OUC5
NIH-3T3 MWnLbY5ie2ViQYPzZZk> NYHYSo52OSCq MWDEUXNQ Mnu0TY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzDTNVIxPllibYX0ZY51KGW6cILld5Nm\CCjc4Pld5Nm\CCjczDwbI9{eGixLVHMT{Bt\X[nbDD3bZRpKEmFNUCgc4YhOC54Mk[g{txO Ml;YNlQ1OzJ7MEm=
NIH-3T3 MnzaT4lv[XOnIFHzd4F6 NULNdFVoOSCq NVK3[Y93TE2VTx?= M4ftPGlvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugUFEyQT[PIH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDBwOESzJO69VQ>? MX:yOFQ{OjlyOR?=
NIH-3T3 NITq[XNMcW6jc3WgRZN{[Xl? M3PKcFEhcA>? M3LEfmROW09? NFvnc4FKdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJGwyOTV{UjDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iBzLkCyOkDPxE1? Ml\TNlQ1OzJ7MEm=
BAF3 M36x[WZ2dmO2aX;uJGF{e2G7 M3rqVVczKGh? NX7UZoRXTE2VTx?= M2e3cGlvcGmkaYTpc44hd2ZiTmDNM2FNUyC2cnHud4Zm[3SnZDDhd5Nme3OnZDDhd{Bk\WyuIHfyc5d1cCCrbnjpZol1cW:wIIfpeIghUUN3MDDv[kAxNjB3MTFOwG0> Mk\uNlQ1Pjh4M{K=
BAF3 M4LlfGN6fG:2b4jpZ{BCe3OjeR?= M3rCe|czKGh? NUe2eYF{TE2VTx?= NHntco1KSzVyPUCuPVgh|ryP NGHtUJAzPDR4OE[zNi=>
NIH-3T3 MofrT4lv[XOnIFHzd4F6 NYXm[2pCOSCq MmXOTY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzDGNVE4PExibYX0ZY51KGW6cILld5Nm\CCjc4Pld5Nm\CCjczDwbI9{eGixLVHMT{Bt\X[nbDD3bZRpKEmFNUCgc4YhOC5zNkWg{txO NF;IblczPDhzOUGxOi=>
NIH-3T3 MWfLbY5ie2ViQYPzZZk> M4SzR|EhcA>? MnLkTY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzDDNVE2PllibYX0ZY51KGW6cILld5Nm\CCjc4Pld5Nm\CCjczDwbI9{eGixLVHMT{Bt\X[nbDD3bZRpKEmFNUCgc4YhOC52N{ig{txO NEfpU44zPDhzOUGxOi=>
NIH-3T3 Mk\3T4lv[XOnIFHzd4F6 M1rUUlEhcA>? MkTFTY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzDHNVIxOlJibYX0ZY51KGW6cILld5Nm\CCjc4Pld5Nm\CCjczDwbI9{eGixLVHMT{Bt\X[nbDD3bZRpKEmFNUCgc4YhOS5zNEig{txO NGnDUYgzPDhzOUGxOi=>
NIH-3T3 NUX5PWszU2mwYYPlJGF{e2G7 NHfCRWEyKGh? M1T2TGlvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugNVE2OVSrboOgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMz6wN|kh|ryP MmrYNlQ5OTlzMU[=
KARPAS299 NUDtPHBLU2mwYYPlJGF{e2G7 NILINIM6OCCvaX6= MX\EUXNQ MVzJcohq[mm2aX;uJI9nKE6STT3meZNm\CCDTFugdIhwe3Cqb4L5cIF1cW:wIHX4dJJme3OnZDD3bZRpKEmFNUCgc4YhOC5zMTFOwG0> Mnr1NlQ6ODB5NUC=
MKN 45 M33CRWtqdmG|ZTDBd5NigQ>? Ml3oNUBp MUTEUXNQ NFy4boVKdmirYnn0bY9vKG:oIHOtUYV1KHCqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6wNkDPxE1? MX[yOFkxODd3MB?=
A549 MmLFR5l1d3SxeHnjJGF{e2G7 MlznOFghcA>? NVLVeJVrTE2VTx?= MWLJR|UxKG:oIESuNFg1KM7:TR?= M4HNZVI1QTByOEOw
NCI-H1975 MX3DfZRwfG:6aXOgRZN{[Xl? NX7lOlVIPDhiaB?= MmfFSG1UVw>? MmrLTWM2OCCxZjC3MlU2OSEQvF2= MYKyOFkxODh|MB?=
NCI-H1993 MVjDfZRwfG:6aXOgRZN{[Xl? MmjyOFghcA>? NELJOJBFVVOR NFmxRmZKSzVyIH;mJFAvODZzIN88US=> NFrlUnUzPDlyMEizNC=>
NCI-H1993 M2jWOGFxd3Sxc3nzJGF{e2G7 Moi4NUDPxE1? Ml\INlQhcA>? MXfEUXNQ NUDXcFh6\G:nczDuc5QhcW6mdXPlJIFxd3C2b4Ppdy=> MlPhNlQ6ODB6M{C=
NIH-3T3 MkfhR5l1d3SxeHnjJGF{e2G7 MoLrOFghcA>? M1;weWROW09? NUPmXWxQUUN3MDDv[kAxNjN4NDFOwG0> NVrTWG9UOjR7MEC4N|A>
EBC1 MnH0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2XQe|czKGh? NVuxeVFDTE2VTx?= NV;mcZlWUUN3MDDv[kAxNjByNkmg{txO M{LMNFI1QTByOEOx
KARPAS299 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoHhO|IhcA>? MWHEUXNQ M{Tvb2lEPTBib3[gNE4zKM7:TR?= MYCyOFkxODh|MR?=
NB1 M1rRPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NInzSnJKSzVyPUmxMlk5KG6P MlqwV2FPT0WU
NCI-SNU-5 NE\vTWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYXJR|UxRTFyNT63OUBvVQ>? MVXTRW5ITVJ?
SR NFnLT3FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1n5XGlEPTB;MUK2MlMyKG6P NH;xWodUSU6JRWK=
SF539 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkT6TWM2OD1{MESuNlQhdk1? MYjTRW5ITVJ?
SU-DHL-1 NEHHdJNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFP5PGNKSzVyPUOzOk45OiCwTR?= NYPqUIpTW0GQR1XS
SCC-3 MnLHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1e0eGlEPTB;M{W2Mlc3KG6P NFjyWmVUSU6JRWK=
DEL NIi0OYRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWrWU4tHUUN3ME2zOlkvQSCwTR?= MlnoV2FPT0WU
CTV-1 NXLUNpp7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGDuTG1KSzVyPUW5Ok41QCCwTR?= NX6yelhoW0GQR1XS
EM-2 MlvyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH7yepFKSzVyPU[wNU4{PCCwTR?= MoHvV2FPT0WU
MHH-CALL-2 NYrGSVJQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnPvTWM2OD14OEKuOVchdk1? NXfhXXo1W0GQR1XS
KM12 NX7sbZZuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVLJR|UxRTdyNj65JI5O Mk\wV2FPT0WU
KINGS-1 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX\5eWVjUUN3ME23OFkvPzVibl2= M2nzN3NCVkeHUh?=
MEG-01 NU\FSpY3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnvUTWM2OD16NUeuOlYhdk1? NEfrc5ZUSU6JRWK=
BV-173 MofZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NITMUllKSzVyPUGuNFU6QTdizszN M2LVeHNCVkeHUh?=
LAMA-84 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmT2TWM2OD1zLkO4NlgzKM7:TR?= MUPTRW5ITVJ?
KARPAS-299 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M172UmlEPTB;MT60NFg3OSEQvF2= M{G4WXNCVkeHUh?=
K-562 M4rMVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUmzZZVFUUN3ME2xMlczOjZ7IN88US=> NXiydW9IW0GQR1XS
SK-LMS-1 NEPR[pdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlzVTWM2OD1zLke2PFY4KM7:TR?= MlzPV2FPT0WU
MOLT-16 M{e0WWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXq0epN7UUN3ME2xMlk2PTd3IN88US=> M3\hXnNCVkeHUh?=
CMK Mn72S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXrVUXdwUUN3ME2xMlk3OTV7IN88US=> M2DUTHNCVkeHUh?=
ST486 Mnm2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3\hZWlEPTB;Mj60N|A4OyEQvF2= MlXGV2FPT0WU
CI-1 M4LiT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NU\nRmt6UUN3ME2yMlQ6PjV7IN88US=> NXe4RoFIW0GQR1XS
KP-N-RT-BM-1 MkO0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mmm2TWM2OD1{LkewNVIzKM7:TR?= NGT0PFlUSU6JRWK=
ALL-PO NFT6bFJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXXJR|UxRTNwMUiyNFch|ryP MXzTRW5ITVJ?
KS-1 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2n3RWlEPTB;Mz6yNVIzPSEQvF2= NFL2cpdUSU6JRWK=
Becker MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml\VTWM2OD12LkKzPVMh|ryP MkHoV2FPT0WU
GDM-1 MlToS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{m3ZmlEPTB;ND6yOFYyPyEQvF2= Mm\RV2FPT0WU
BC-1 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVHJR|UxRTRwNEmyO|ch|ryP M{\aPHNCVkeHUh?=
NB14 MoDiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHrX[IVKSzVyPUSuPFM2OjRizszN NID5[ZNUSU6JRWK=
NOS-1 MmXOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Moj0TWM2OD13LkOzPFc1KM7:TR?= NYfVOYdFW0GQR1XS
MZ1-PC NUPwSotqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWXJR|UxRTVwOEKxOVEh|ryP NGOxZnVUSU6JRWK=
A498 NVq0[4U6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3TEbGlEPTB;Nj6wPFQ4OyEQvF2= NYjOfGREW0GQR1XS
EW-16 MoLhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoDBTWM2OD14LkO3O|c{KM7:TR?= MVnTRW5ITVJ?
NALM-6 NHvlNG1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NES4c|BKSzVyPU[uOlg{QDdizszN MnvQV2FPT0WU
EB-3 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX;YfmZQUUN3ME23MlA4OjN|IN88US=> NHLKdW1USU6JRWK=
697 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFGwPY5KSzVyPUmuNlQ{OjlizszN NIH2eoJUSU6JRWK=
Ramos-2G6-4C10 M1rWN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mmn1TWM2OD17LkW5PFQzKM7:TR?= MoW3V2FPT0WU
KNS-81-FD MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYPJR|UxRTlwNkm2OVMh|ryP NIPRZ5VUSU6JRWK=
HUTU-80 M4TmO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWnJR|UxRTlwN{S2OFIh|ryP NYLQSXQ{W0GQR1XS
LS-411N NIrtRXhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NInWWVJKSzVyPUGwMlA2PjdizszN MljkV2FPT0WU
RPMI-8402 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWr3c29OUUN3ME2xNE4yOTZizszN Mo\VV2FPT0WU
KU812 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV\JR|UxRTFyLkK5PVEh|ryP NFjS[2NUSU6JRWK=
EW-1 MlfJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmXLTWM2OD1zMD60OFI2KM7:TR?= NYLKXo97W0GQR1XS
HC-1 MoLnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmC3TWM2OD1zMD60PFQ1KM7:TR?= NVv6NnliW0GQR1XS
NB69 MnHXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF:yUHpKSzVyPUGwMlUxPDNizszN M{HUfHNCVkeHUh?=
MFH-ino NI\IT5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUT3O3NIUUN3ME2xNE45OzB|IN88US=> M{fROXNCVkeHUh?=
CCRF-CEM MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFO0U4FKSzVyPUGxMlU6PyEQvF2= NFrDZW5USU6JRWK=
SK-N-DZ NXrQcGVLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3\YcmlEPTB;MUKuNFQ{PiEQvF2= MoXSV2FPT0WU
NCI-H720 NU\HeXF6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3T2UWlEPTB;MUKuNVcxPSEQvF2= MkS1V2FPT0WU
HCC1187 MlvhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MljYTWM2OD1zMj6yNFQyKM7:TR?= MoTyV2FPT0WU
IST-SL2 MknJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4fCbGlEPTB;MUKuOFg4OiEQvF2= NIL0b|FUSU6JRWK=
KE-37 MlrHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXTzXJplUUN3ME2xNk44QTZ4IN88US=> MYLTRW5ITVJ?
HCC1599 MnvES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYfJR|UxRTF{LkmwOlkh|ryP MV\TRW5ITVJ?
A4-Fuk NGfDOVBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{XKcGlEPTB;MUKuPVU5PiEQvF2= M{fCfnNCVkeHUh?=
NKM-1 M4XUSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGrQWIpKSzVyPUGzMlI6OjVizszN NFTCRoNUSU6JRWK=
BE-13 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHm4W2JKSzVyPUGzMlc6QDlizszN MlvxV2FPT0WU
MV-4-11 M1TrU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4Ha[mlEPTB;MUSuNFMzPCEQvF2= NWHP[FF5W0GQR1XS
OPM-2 MlnzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVTJR|UxRTF2LkSwPFUh|ryP MUTTRW5ITVJ?
KARPAS-422 MlvLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmjKTWM2OD1zND61NVI3KM7:TR?= MUnTRW5ITVJ?
RPMI-8226 M4n3[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NY\Wc5dsUUN3ME2xOE45QTF3IN88US=> M{D5R3NCVkeHUh?=
KARPAS-45 Mn3kS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXq1Z4JuUUN3ME2xOU44PzF4IN88US=> NGjGUphUSU6JRWK=
SK-PN-DW NH7vc2JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVS5W21mUUN3ME2xOU45PjNzIN88US=> M1rqT3NCVkeHUh?=
LC-2 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mnu3TWM2OD1zNj6xOVA3KM7:TR?= NIrUcpNUSU6JRWK=
NCI-H1648 M4fSb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGnLfphKSzVyPUG2MlI2PCEQvF2= NITMfmxUSU6JRWK=
RL95-2 M3nQc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1T0VGlEPTB;MU[uN|k4QCEQvF2= MkLaV2FPT0WU
KNS-42 Mn[2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIfPZnpKSzVyPUG2MlczPzRizszN NEn1blRUSU6JRWK=
RPMI-6666 M{jiZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4LSVmlEPTB;MU[uPVIyOSEQvF2= MmXqV2FPT0WU
SIG-M5 M3LxV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWjrfVNOUUN3ME2xO{4yQTB|IN88US=> MnvmV2FPT0WU
VA-ES-BJ NEe1PZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFvPNY5KSzVyPUG3Mlc1PTFizszN NUfJdFFbW0GQR1XS
MONO-MAC-6 NGXRbYNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYLKTnZYUUN3ME2xO{46OzF{IN88US=> NX\VVVdsW0GQR1XS
LAN-6 NH[2d5RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnXJTWM2OD1zOD63OVU4KM7:TR?= NEPhU|NUSU6JRWK=
A388 NIXFfZdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoTuTWM2OD1zOT6zNFU6KM7:TR?= M1HPTHNCVkeHUh?=
SK-NEP-1 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmnnTWM2OD1{MD6yNVMzKM7:TR?= Mo\DV2FPT0WU
TE-10 Mkn3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmjxTWM2OD1{MD61NlIyKM7:TR?= M4G4[3NCVkeHUh?=
HL-60 NF\VfJlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVLNZlFoUUN3ME2yNE46ODl7IN88US=> NHzBTlJUSU6JRWK=
MC116 NXKwRmFIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXG4Uo1ZUUN3ME2yNU44OjJzIN88US=> NG[0WpNUSU6JRWK=
SW962 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWXJR|UxRTJzLke5NVUh|ryP MYLTRW5ITVJ?
NOMO-1 NGDyRYNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUjJR|UxRTJ{Lk[1OlQh|ryP MU\TRW5ITVJ?
CTB-1 M2jHWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1;yWWlEPTB;MkKuPFY4OSEQvF2= NGHOTo9USU6JRWK=
MRK-nu-1 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYLJR|UxRTJ{LkmwO|Qh|ryP NInqOFVUSU6JRWK=
GR-ST NVvFSox5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWDJR|UxRTJ|Lke2JO69VQ>? MmTqV2FPT0WU
HH NGnXU3pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV3JR|UxRTJ2LkCwN{DPxE1? NUjhUXlEW0GQR1XS
NCI-H1963 MoWzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoDmTWM2OD1{ND6wO|gzKM7:TR?= MXHTRW5ITVJ?
QIMR-WIL NWLvdZFpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV:5OpJ3UUN3ME2yOE45Pzd{IN88US=> NYrReWJ6W0GQR1XS
CGTH-W-1 NITZ[oVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkDtTWM2OD1{NT6wO|I{KM7:TR?= M3;kS3NCVkeHUh?=
LP-1 NEDFbI1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWPJR|UxRTJ3Lk[1OVEh|ryP NGD0R|FUSU6JRWK=
NCI-H748 NFrLNHhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnrjTWM2OD1{Nj61NVM4KM7:TR?= NWj5NFVrW0GQR1XS
PF-382 NVPZb|dQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF3tcnNKSzVyPUK3MlIzOjNizszN M4HXXnNCVkeHUh?=
ATN-1 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{TPWGlEPTB;MkeuN|c{OiEQvF2= M1y3OnNCVkeHUh?=
L-540 NH;aWHRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH\ZRoRKSzVyPUK3MlY1PTlizszN NI\ldI1USU6JRWK=
LXF-289 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYr2d|NnUUN3ME2yO{44PTF7IN88US=> NYXkbYk6W0GQR1XS
LS-513 M4X0UGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYDq[5FGUUN3ME2yPE4yQDB5IN88US=> NXrvdllnW0GQR1XS
NCI-H1581 M{DvNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV6xfWdGUUN3ME2zNE4{QTd4IN88US=> M3PuNXNCVkeHUh?=
ES6 NYWxeYdWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmLjTWM2OD1|MD62PFk6KM7:TR?= MknFV2FPT0WU
SW982 Mm\KS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVzVVYhMUUN3ME2zNE45PTZ4IN88US=> NUTpcVU1W0GQR1XS
DOHH-2 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3vKN2lEPTB;M{GuOVg6OyEQvF2= MkHSV2FPT0WU
DB MlrsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUfESINuUUN3ME2zN{46PDNzIN88US=> NWGyN5B4W0GQR1XS
MPP-89 M1HvcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NInJZm9KSzVyPUO0MlE4PTZizszN NHK2PItUSU6JRWK=
LB831-BLC MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFLIW5BKSzVyPUO0MlUyQDRizszN Ml;oV2FPT0WU
NB5 NGTidYJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVvhfoh7UUN3ME2zOE45PTN3IN88US=> NGHFRnlUSU6JRWK=
GB-1 NFnvWmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGLBWVVKSzVyPUO1MlA1PjlizszN NWLMdoN3W0GQR1XS
TE-15 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mmf5TWM2OD1|NT6yNlM5KM7:TR?= NHPzfZFUSU6JRWK=
LC4-1 NUe4S4hMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4i0U2lEPTB;M{WuN|g1PyEQvF2= M2DCT3NCVkeHUh?=
NCI-H747 NVG5NVI3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1;CPGlEPTB;M{[uNVM3QSEQvF2= MWfTRW5ITVJ?
NTERA-S-cl-D1 M1zjOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWXJR|UxRTN6LkezOFch|ryP MoTOV2FPT0WU
SK-MM-2 MoDzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkLRTWM2OD12MD6xNVQ3KM7:TR?= NGjDOGJUSU6JRWK=
TGW MlHjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoSwTWM2OD12MT6wOVY{KM7:TR?= MYXTRW5ITVJ?
ONS-76 M4rRVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnXRTWM2OD12Mj60PFg{KM7:TR?= NFj4[4VUSU6JRWK=
CPC-N Mk[xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MljZTWM2OD12Mj65PVcyKM7:TR?= MWrTRW5ITVJ?
ES4 NWDveItZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVi0N4pSUUN3ME20OE41OTV|IN88US=> MnnOV2FPT0WU
Daudi NVu5T3pwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1nEVGlEPTB;NEWuNFgzPyEQvF2= MXXTRW5ITVJ?
MOLT-4 Mon2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn\wTWM2OD12NT6wPFU{KM7:TR?= NETpRnFUSU6JRWK=
HT-144 M1rIZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEfm[m5KSzVyPUS2MlczPiEQvF2= NUjjd3dvW0GQR1XS
SW872 M2TsXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUXuR4twUUN3ME20PE4yQTN|IN88US=> MWLTRW5ITVJ?
D-283MED M4DC[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkniTWM2OD12OD6zOVQzKM7:TR?= MUPTRW5ITVJ?
NCI-H2126 MmTSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXjZPVB3UUN3ME20PE45PDd4IN88US=> MVHTRW5ITVJ?
NCI-SNU-16 NHvFWYdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWr5Ono1UUN3ME20PU4zOTR|IN88US=> M4PSXXNCVkeHUh?=
CESS MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NY\iS5dPUUN3ME20PU42ODh6IN88US=> NYC0dIhRW0GQR1XS
A101D NX7wcHNLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV;nTpE2UUN3ME20PU46PzN4IN88US=> MoH1V2FPT0WU

... 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

Bio Calculators

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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