Crizotinib (PF-02341066) Licensed by Pfizer

Catalog No.S1068

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.

Price Stock Quantity  
USD 220 In stock
USD 110 In stock
USD 170 In stock
USD 570 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

Crizotinib (PF-02341066) Chemical Structure

Crizotinib (PF-02341066) Chemical Structure
Molecular Weight: 450.34

Validation & Quality Control

Cited by 65 publications:

8 customer reviews :

Quality Control & MSDS

Related Compound Libraries

c-Met Inhibitors with Unique Features

  • Selective c-Met Inhibitor

    PF-04217903 C-Met-selective, IC50=4.8 nM.

  • Most Potent c-Met Inhibitor

    INCB28060 C-Met, IC50=0.13 nM.

  • c-Met Inhibitor in Clinical Trial

    Tivantinib (ARQ 197) Phase III for Hepatocellular Carcinoma.

  • Newest c-Met Inhibitor

    EMD 1214063 Potent and selective c-Met inhibitor with IC50 of 4 nM, >200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer.

Product Information

  • Compare c-Met Inhibitors
    Compare c-Met Products
  • Research Area
  • Crizotinib (PF-02341066) Mechanism
  • Combination Therapy
    Combination Therapy

Product Description

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.
Targets c-Met [1]
(A549, MDA-MB-231, GTL-16, HT29, 786-O, Colo-205, A498 cells)
ALK [1]
(Karpas299 cells)
IC50 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 LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
BAF3MYfDfZRwfG:6aXOgRZN{[Xl?MXm0PEBpNH70RXlFVVORMVPDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRWY{KGOnbHzzJIV5eHKnc4PpcochSUyNIF[xNVc1VCCvdYThcpQh[2:neIDy[ZN{cW6pIFXNUFQhf2m2aDDJR|UxKG:oIECuOlIh|ryPNEHjT4ozOTV5MkW4PS=>
BAF3NGPlNZdEgXSxdH;4bYMhSXO|YYm=MYe0PEBpMWLEUXNQM4DQXmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KG2xdYPlJGJCTjNiY3XscJMh\XiycnXzd4lv\yCDTFugUFEyQT[PIH31eIFvfCClb3X4dJJme3OrbnegSW1NPCC5aYToJGlEPTBib3[gNk4zKM7:TR?=NUfyNFljOjF3N{K1PFk>
BAF3NHLNWHlEgXSxdH;4bYMhSXO|YYm=NWXkUGE1PDhiaB?=MlPCSG1UVw>?MonmR5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmFHOyClZXzsd{BmgHC{ZYPzbY5oKEWPTEStRWxMKHerdHigTWM2OCCxZjCwMlI5KM7:TR?=NHvsUVQzOTV5MkW4PS=>
KellyMnzkR5l1d3SxeHnjJGF{e2G7M13CNmROW09?NIjveGlEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBM\WyueTDj[YxteyCneIDy[ZN{cW6pIFHMT{BHOTF5NFygcZV1[W62IIfpeIghUUN3MDDv[kAxNjR{IN88US=>M1TWVVIyPTd{NUi5
SH-SY5YNYrYToN6S3m2b4TvfIlkKEG|c3H5M1fSXmROW09?NYLZTmlsS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hW0hvU2m1XUBk\WyuczDlfJBz\XO|aX7nJGFNUyCIMUG3OGwhdXW2YX70JJdqfGhiSVO1NEBw\iByLkWzJO69VQ>?NGPYR4YzOTV5MkW4PS=>
SMS-KCNNULP[nJIS3m2b4TvfIlkKEG|c3H5NGX0R5dFVVORNUixeGd{S3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hW02VLVvDUkBk\WyuczDlfJBz\XO|aX7nJGFNUyCUMUK3OXEhdXW2YX70JJdqfGhiSVO1NEBw\iByLkmxJO69VQ>?MmK5NlE2PzJ3OEm=
BAF3NGHJfpVEgXSxdH;4bYMhSXO|YYm=NIrlcnI1QCCqNIC4XGFFVVORNEHLTo1EgXSxdH;4bYNqfHliYXfhbY5{fCCvb4Xz[UBDSUZ|IHPlcIx{KGW6cILld5NqdmdiVHXsMWFNUyC5aYToJGlEPTBib3[gNE4yQSEQvF2=MWGyNVU4OjV6OR?=
3T3NF7tTldHfW6ldHnvckBCe3OjeR?=MoTkNUBpMULEUXNQM{\i[mlvcGmkaYTpc44hd2ZiUl;OJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iByLkC4JO69VQ>?NEXLXlYzOThzMkSxOC=>
3T3-ENY\wSJhUTnWwY4Tpc44hSXO|YYm=MmP2NUBpNIO4RnBFVVORNXPte3JxUW6qaXLpeIlwdiCxZjDUTWUzKGG|c3Xzd4VlKGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iByLkS0PEDPxE1?MV[yNVgyOjRzNB?=
A549NHq2Oo9McW6jc3WgRZN{[Xl?M2PYdFEhcA>?NGKxbYRFVVORMX\Jcohq[mm2aX;uJI9nKGi3bXHuJJJm[2:vYnnuZY51KGNvTVXUJItqdmG|ZTDlfJBz\XO|ZXSgZZN{\XO|ZXSgZZMhcW6qaXLpeIlwdiCxZjDIS2YucW6mdXPl[EBifXSxcHjvd5Bpd3K7bHH0bY9vKHerdHigTWM2OCCxZjCwMlAxQCEQvF2=NULWSIN[OjF6MUK0NVQ>
BAF3-BCLMlnMSpVv[3Srb36gRZN{[Xl?MWCxJIg>MUDEUXNQNHjIZYlKdmirYnn0bY9vKG:oIFHCUEBie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMT6xOVkh|ryPM1nZNFIyQDF{NEG0
HEK293NFrwSXFHfW6ldHnvckBCe3OjeR?=MoT4NUBpM3m3cmROW09?MXfJcohq[mm2aX;uJI9nKEG[TDDhd5Nme3OnZDDhd{Boem:5dHig[oFkfG:{LXnu[JVk\WRiYYX0c5Bpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOC5{OUSg{txOM131[FIyQDF{NEG0
HEK293NEj1VXVHfW6ldHnvckBCe3OjeR?=M4TSS|EhcA>?M{LBfmROW09?M4LJR2lvcGmkaYTpc44hd2ZiSWKgZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDJwOEi3JO69VQ>?MVqyNVgyOjRzNB?=
JurkatNFjabHpHfW6ldHnvckBCe3OjeR?=M1L5VFEhcA>?NFTjSoZFVVORMV;Jcohq[mm2aX;uJI9nKEyFSzDhd5Nme3OnZDDhd{Boem:5dHig[oFkfG:{LXnu[JVk\WRiYYX0c5Bpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOi55NEGg{txOM2DJPFIyQDF{NEG0
KARPAS299MUPLbY5ie2ViQYPzZZk>M4PDOVEhcA>?NVG2N4lPTE2VTx?=MoHnTY5pcWKrdHnvckBw\iCDTFugZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwMEKg{txOMmLyNlE5OTJ2MUS=
PAEMlqzSpVv[3Srb36gRZN{[Xl?NXrV[|lWOSCqMn;mSG1UVw>?M2LTO2lvcGmkaYTpc44hd2ZiVGLLRkBie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6zPVkh|ryPNVn3RnNLOjF6MUK0NVQ>
BAF3MmXySpVv[3Srb36gRZN{[Xl?NYPOSWUyOi1|IHS=MYDEUXNQNWfVdoFRUW6qaXLpeIlwdiCxZjDUSWwu\nW|ZXSgbY5{fWyrbjDy[YNmeHSxcjDlfJBz\XO|ZXSge4l1cCCLQ{WwJI9nKDFwNkSzJO69VQ>?MY[yN|c1OjJ3Mh?=
KARPAS299NXy5TFJNS3m2b4TvfIlkKEG|c3H5NEPsd4UzNTNiZB?=NFXCWIlFVVORNYrHe|k2UUN3ME2wMlA3PDJizszNNXr4VXh6OjN5NEKyOVI>
EBC1M2S5Omdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NH31PVY4OiCqMl7wSG1UVw>?MnvwTWM2OD1yLkCyN{DPxE1?MYeyN|k6OzN{OB?=
HCT116NXzGNY5yT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M4rrPVczKGh?NIqw[oVFVVORNECxWWFKSzVyPUG0MlgzKM7:TR?=MVuyN|k6OzN{OB?=
MCF7M2fPWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MX63NkBpMkHCSG1UVw>?NEP4[ohKSzVyPUmuOVgh|ryPNUPsS4xSOjN7OUOzNlg>
MDA-MB-231M2S2V2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NE\pVm84OiCqMlHZSG1UVw>?NIjGS25KSzVyPUGwMlgh|ryPMVeyN|k6OzN{OB?=
MKN45MmPtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MoexO|IhcA>?MUDEUXNQM3\aSmlEPTB;MD6wNVMh|ryPNWHzeYdqOjN7OUOzNlg>
NCI-H441MlrBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NG\F[po4OiCqMkDESG1UVw>?MlexTWM2OD1zNz6yOUDPxE1?NFmyNmIzOzl7M{OyPC=>
NCI-H661NHK4N3dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MVy3NkBpMX7EUXNQM{\xdWlEPTB;MUGuOFch|ryPMVGyN|k6OzN{OB?=
SK-MEL-28MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MVq3NkBpM{LlSWROW09?NWniXoxvUUN3ME2xNE46PyEQvF2=MnnMNlM6QTN|Mki=
SKOV3M1XQfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NV3uclI5PzJiaB?=M2PIdGROW09?NX23R2I5UUN3ME2xNk45PSEQvF2=NXnkd2lEOjN7OUOzNlg>
SNU5MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MX23NkBpM1H1dGROW09?NWHSeYJzUUN3ME2wMlAyPiEQvF2=MmKxNlM6QTN|Mki=
NCI-H2228M1HvVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MYS3NkBpNHzm[YdFVVORNHrlS|hKdmirYnn0bY9vKG:oIFHMT{1nfXOrb36g[JJqfmWwIHPlcIwheHKxbHnm[ZJifGmxbjD3bZRpKEmFNUCgc4YhOC5zMUig{txOMXSyOFQ{OjlyOR?=
NCI-H3122NXnlfmF6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NWn1Z3lPPzJiaB?=MmrkSG1UVw>?NUfqWIZNUW6qaXLpeIlwdiCxZjDBUGsu\nW|aX;uJIRzcX[nbjDj[YxtKHC{b3zp[oVz[XSrb36ge4l1cCCLQ{WwJI9nKDBwMUC4JO69VQ>?MX6yOFQ{OjlyOR?=
NCI-H3122MkX3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NGn5WGw4OiCqM2HMN2ROW09?NUTIepQ5UW6qaXLpeIlwdiCxZjDBUGsu\nW|aX;uJIRzcX[nbjDj[YxtKHC{b3zp[oVz[XSrb36gbY4hcHWvYX6gUmNKNUh|MUKyJINmdGy|IHjhdoJwemmwZzDBUGshTzF{NknBJI12fGGwdDD3bZRpKEmFNUCgc4YhOC54MkOg{txOMlfrNlQ1OzJ7MEm=
NCI-H3122NWHsNG04T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NI\NTmI4OiCqM33WUGROW09?M1G4dGlvcGmkaYTpc44hd2ZiQVzLMYZ2e2mxbjDkdol3\W5iY3XscEBxem:uaX\ldoF1cW:wIHnuJIh2dWGwIF7DTU1JOzF{MjDj[YxteyCqYYLic5JqdmdiQVzLJGwyOTl4TTDteZRidnRid3n0bEBKSzVyIH;mJFAvQDN6IN88US=>M4LIR|I1PDN{OUC5
NIH-3T3MVTLbY5ie2ViQYPzZZk>MX6xJIg>M1vINGROW09?MmT0TY5pcWKrdHnvckBw\iCqdX3hckB4cWymIIT5dIUhTU2OND3meZNm\CCDTFug[ZhxemW|c3XkJIF{e2W|c3XkJIF{KHCqb4PwbI9zgWyjdHXkJGFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMD6wPEDPxE1?NXrNRmpOOjR2M{K5NFk>
NIH-3T3MmftT4lv[XOnIFHzd4F6Mk\CNUBpNYfTclBrTE2VTx?=NVjUc2VsUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BIOTJ4OVGgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMD62NFUh|ryPMV6yOFQ{OjlyOR?=
NIH-3T3NWPOcXNWU2mwYYPlJGF{e2G7MlXPNUBpNF;tUVFFVVORNFLrfItKdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJHMyOjB4WTDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLk[yOkDPxE1?NUPWVI4zOjR2M{K5NFk>
NIH-3T3MVTLbY5ie2ViQYPzZZk>NHPYVYsyKGh?M{\5VmROW09?NVLl[5Q1UW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BNOTF7Nl2gcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMD64OFMh|ryPMWWyOFQ{OjlyOR?=
NIH-3T3M3ixO2tqdmG|ZTDBd5NigQ>?NGL4N5AyKGh?NWLheWJMTE2VTx?=NY\2dlhDUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BNOTF3MmKgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMT6wNlYh|ryPNHHHXY4zPDR|MkmwPS=>
BAF3NH3wfINHfW6ldHnvckBCe3OjeR?=M3O3T|czKGh?MmPGSG1UVw>?MUHJcohq[mm2aX;uJI9nKE6STT;BUGshfHKjboPm[YN1\WRiYYPz[ZN{\WRiYYOgZ4VtdCCpcn;3eIghcW6qaXLpeIlwdiC5aYToJGlEPTBib3[gNE4xPTFizszNM3LnXFI1PDZ6NkOy
BAF3M4ryfGN6fG:2b4jpZ{BCe3OjeR?=NWjMUFJxPzJiaB?=NVfMboxjTE2VTx?=M124W2lEPTB;MD65PEDPxE1?MYeyOFQ3QDZ|Mh?=
NIH-3T3NEHSOYJMcW6jc3WgRZN{[Xl?NYrsVJNWOSCqMl:zTY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzDGNVE4PExibYX0ZY51KGW6cILld5Nm\CCjc4Pld5Nm\CCjczDwbI9{eGixLVHMT{Bt\X[nbDD3bZRpKEmFNUCgc4YhOC5zNkWg{txOMmPKNlQ5OTlzMU[=
NIH-3T3M3PuUGtqdmG|ZTDBd5NigQ>?MVyxJIg>MUTJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIFOxNVU3YSCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAxNjR5ODFOwG0>NUH6[HVROjR6MUmxNVY>
NIH-3T3NHTFWXhMcW6jc3WgRZN{[Xl?NULz[pVFOSCqNXfmUlVSUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BIOTJyMmKgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMT6xOFgh|ryPMmPNNlQ5OTlzMU[=
NIH-3T3NIjhe|JMcW6jc3WgRZN{[Xl?M2DQXVEhcA>?MXHJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIEGxOVFVcW6|IH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDNwMEO5JO69VQ>?NX\sZnpEOjR6MUmxNVY>
KARPAS299M3PQU2tqdmG|ZTDBd5NigQ>?NVHmc|B1QTBibXnuNGf2ZZNFVVORNY[z[|EzUW6qaXLpeIlwdiCxZjDOVG0u\nW|ZXSgRWxMKHCqb4PwbI9zgWyjdHnvckBmgHC{ZYPz[YQhf2m2aDDJR|UxKG:oIECuNVEh|ryPNXLEN5pkOjR7MEC3OVA>
MKN 45MkLkT4lv[XOnIFHzd4F6M2\2OVEhcA>?MULEUXNQMm\jTY5pcWKrdHnvckBw\iClLV3leEBxcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwMEKg{txOM3v4[VI1QTByN{Ww
A549NGDaS3lEgXSxdH;4bYMhSXO|YYm=MVq0PEBpM360WWROW09?NHjkTpZKSzVyIH;mJFQvODh2IN88US=>NIPW[FgzPDlyMEizNC=>
NCI-H1975NUTDUI9uS3m2b4TvfIlkKEG|c3H5MkfpOFghcA>?MmrKSG1UVw>?NWnnXWNuUUN3MDDv[kA4NjV3MTFOwG0>NWPaZ2Z6OjR7MEC4N|A>
NCI-H1993NW\aUVlyS3m2b4TvfIlkKEG|c3H5NXzSVJA4PDhiaB?=NYqxZWRkTE2VTx?=NFzBVGhKSzVyIH;mJFAvODZzIN88US=>M4O1OFI1QTByOEOw
NCI-H1993MlXzRZBwfG:|aYOgRZN{[Xl?NInYOlAyKM7:TR?=MYeyOEBpMU\EUXNQNFq1W21ld2W|IH7veEBqdmS3Y3WgZZBweHSxc3nzNV\RNG02OjR7MEC4N|A>
NIH-3T3NX[yNZlpS3m2b4TvfIlkKEG|c3H5M17ubFQ5KGh?M2TVWWROW09?MVvJR|UxKG:oIECuN|Y1KM7:TR?=M2LEOVI1QTByOEOw
EBC1MmO4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?Ml7xO|IhcA>?M3T1OGROW09?M2O1fWlEPTBib3[gNE4xODZ7IN88US=>NVnxZm15OjR7MEC4N|E>
KARPAS299NX3SWWF1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NEDXVoQ4OiCqNFztZWtFVVORNF7pZ|VKSzVyIH;mJFAvOiEQvF2=NF:zV3MzPDlyMEizNS=>
NB1M{XSTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MmDhTWM2OD17MT65PEBvVQ>?MVLTRW5ITVJ?
NCI-SNU-5NG\KPVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M4XibmlEPTB;MUC1Mlc2KG6PNF7BSFdUSU6JRWK=
SRM2\3ZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7Mm\DTWM2OD1zMk[uN|Ehdk1?MUXTRW5ITVJ?
SF539MmTOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MnT4TWM2OD1{MESuNlQhdk1?NHjKcItUSU6JRWK=
SU-DHL-1NULRcnVGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NYT4ZlJYUUN3ME2zN|YvQDJibl2=MVjTRW5ITVJ?
SCC-3NYTUSJdlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NFvNbFhKSzVyPUO1Ok44PiCwTR?=MlK2V2FPT0WU
DELMVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MoPrTWM2OD1|NkmuPUBvVQ>?NVTqVolPW0GQR1XS
CTV-1MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NGXsZ5JKSzVyPUW5Ok41QCCwTR?=M3LZVHNCVkeHUh?=
EM-2NIXQOFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M4LlfGlEPTB;NkCxMlM1KG6PM2HXUXNCVkeHUh?=
MHH-CALL-2NI[yPHRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M1\PfmlEPTB;NkiyMlU4KG6PMkfHV2FPT0WU
KM12NWfTOJR[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M2HXWmlEPTB;N{C2Mlkhdk1?M{DyS3NCVkeHUh?=
KINGS-1NUXq[IgyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXnXW5JVUUN3ME23OFkvPzVibl2=Mn21V2FPT0WU
MEG-01MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NWfLe3hKUUN3ME24OVcvPjZibl2=NHL6WWdUSU6JRWK=
BV-173NVrXXJhiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NIjteFZKSzVyPUGuNFU6QTdizszNM2HzZnNCVkeHUh?=
LAMA-84MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MYXJR|UxRTFwM{iyPFIh|ryPMWrTRW5ITVJ?
KARPAS-299MkXSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NXjsT5JNUUN3ME2xMlQxQDZzIN88US=>M3;YUnNCVkeHUh?=
K-562NUDwbmMyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NH7hWJZKSzVyPUGuO|IzPjlizszNM4\KbXNCVkeHUh?=
SK-LMS-1NFL6[2tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MmK0TWM2OD1zLke2PFY4KM7:TR?=NVXzT5JqW0GQR1XS
MOLT-16MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MnjYTWM2OD1zLkm1OVc2KM7:TR?=MmLoV2FPT0WU
CMKMUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?Mn\0TWM2OD1zLkm2NVU6KM7:TR?=MXnTRW5ITVJ?
ST486NITJe3NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MlfwTWM2OD1{LkSzNFc{KM7:TR?=M3S3NnNCVkeHUh?=
CI-1M2PweGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MnHsTWM2OD1{LkS5OlU6KM7:TR?=MlPkV2FPT0WU
KP-N-RT-BM-1NWH5XYhMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M3XI[mlEPTB;Mj63NFEzOiEQvF2=M4riN3NCVkeHUh?=
ALL-POM1P6cGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NEPr[5pKSzVyPUOuNVgzODdizszNNIiwclhUSU6JRWK=
KS-1NUHvTo5FT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MoTFTWM2OD1|LkKxNlI2KM7:TR?=M2n0ZXNCVkeHUh?=
BeckerMonnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MVzJR|UxRTRwMkO5N{DPxE1?NUnz[HV[W0GQR1XS
GDM-1NXe0UGFVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NIHFOpVKSzVyPUSuNlQ3OTdizszNNGize|dUSU6JRWK=
BC-1NFTWWItIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MV\JR|UxRTRwNEmyO|ch|ryPMWPTRW5ITVJ?
NB14MlvwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MlrCTWM2OD12LkizOVI1KM7:TR?=M371ZXNCVkeHUh?=
NOS-1MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M1LMNmlEPTB;NT6zN|g4PCEQvF2=Mo[wV2FPT0WU
MZ1-PCNILpXpFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MWDJR|UxRTVwOEKxOVEh|ryPMkTVV2FPT0WU
A498MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M2i1eGlEPTB;Nj6wPFQ4OyEQvF2=NH;mbnlUSU6JRWK=
EW-16M{jOTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NGHvU3JKSzVyPU[uN|c4PzNizszNNFvTRVVUSU6JRWK=
NALM-6M1SwSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MnnOTWM2OD14Lk[4N|g4KM7:TR?=NGXoTGVUSU6JRWK=
EB-3MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?Mn3mTWM2OD15LkC3NlM{KM7:TR?=MoLBV2FPT0WU
697Ml\TS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MlHXTWM2OD17LkK0N|I6KM7:TR?=M2XzNXNCVkeHUh?=
Ramos-2G6-4C10M{jZ[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NVjmdXFoUUN3ME25MlU6QDR{IN88US=>MV\TRW5ITVJ?
KNS-81-FDMVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MkfQTWM2OD17Lk[5OlU{KM7:TR?=NEG5bopUSU6JRWK=
HUTU-80NYHVO5lMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MVXJR|UxRTlwN{S2OFIh|ryPMnnPV2FPT0WU
LS-411NNWrkO4xUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=Mo\xTWM2OD1zMD6wOVY4KM7:TR?=NWfaNW41W0GQR1XS
RPMI-8402MnHhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MWPJR|UxRTFyLkGxOkDPxE1?M4XZR3NCVkeHUh?=
KU812M4LXZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7M17vZWlEPTB;MUCuNlk6OSEQvF2=NUHKeoxzW0GQR1XS
EW-1NWC3PVAzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NVHaRVkxUUN3ME2xNE41PDJ3IN88US=>MYLTRW5ITVJ?
HC-1M3q2Vmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NYX0VJJIUUN3ME2xNE41QDR2IN88US=>M{[xdnNCVkeHUh?=
NB69M{PSfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7Mlf2TWM2OD1zMD61NFQ{KM7:TR?=NH3uNnZUSU6JRWK=
MFH-inoNVXlVWFTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NFjISZRKSzVyPUGwMlg{ODNizszNMVnTRW5ITVJ?
CCRF-CEMNHT3R4lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MWrJR|UxRTFzLkW5O{DPxE1?MYDTRW5ITVJ?
SK-N-DZMXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NFjuU25KSzVyPUGyMlA1OzZizszNM3HIfHNCVkeHUh?=
NCI-H720MlraS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NELve2xKSzVyPUGyMlE4ODVizszNM2H0V3NCVkeHUh?=
HCC1187M{XUSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NHjkdHBKSzVyPUGyMlIxPDFizszNM3ryTHNCVkeHUh?=
IST-SL2MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NHPwc5RKSzVyPUGyMlQ5PzJizszNM17oNHNCVkeHUh?=
KE-37NWDadpd5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NIm4WY9KSzVyPUGyMlc6PjZizszNNYHpPYViW0GQR1XS
HCC1599MmjSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MWnJR|UxRTF{LkmwOlkh|ryPMlz6V2FPT0WU
A4-FukMVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MYXJR|UxRTF{Lkm1PFYh|ryPNVfYWndRW0GQR1XS
NKM-1M2PaUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MYrJR|UxRTF|LkK5NlUh|ryPNUm0N|l2W0GQR1XS
BE-13MoTCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MVfJR|UxRTF|Lke5PFkh|ryPNHXPW4hUSU6JRWK=
MV-4-11MmHXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M2DleWlEPTB;MUSuNFMzPCEQvF2=MUXTRW5ITVJ?
OPM-2NH3ON4xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MWTJR|UxRTF2LkSwPFUh|ryPNUHEb20zW0GQR1XS
KARPAS-422MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M3SwdWlEPTB;MUSuOVEzPiEQvF2=MYfTRW5ITVJ?
RPMI-8226MnTXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NIHxTJFKSzVyPUG0Mlg6OTVizszNNGrEe5BUSU6JRWK=
KARPAS-45M4HGeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NInRdYhKSzVyPUG1Mlc4OTZizszNMmfSV2FPT0WU
SK-PN-DWNH3vdFVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MmnXTWM2OD1zNT64OlMyKM7:TR?=Mo\KV2FPT0WU
LC-2M37CbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7Ml7STWM2OD1zNj6xOVA3KM7:TR?=NX7Mbot4W0GQR1XS
NCI-H1648NYnHb45LT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NUT2R5JnUUN3ME2xOk4zPTRizszNM4rvNXNCVkeHUh?=
RL95-2M2rGPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NEH2NmhKSzVyPUG2MlM6PzhizszNNH7RRY9USU6JRWK=
KNS-42Ml71S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NWeyTpE2UUN3ME2xOk44Ojd2IN88US=>MnTKV2FPT0WU
RPMI-6666NH32eVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MmrqTWM2OD1zNj65NlEyKM7:TR?=MmDZV2FPT0WU
SIG-M5Mk[2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?Mn36TWM2OD1zNz6xPVA{KM7:TR?=NWXXbGxCW0GQR1XS
VA-ES-BJNXTqUZU4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MYXJR|UxRTF5Lke0OVEh|ryPMYDTRW5ITVJ?
MONO-MAC-6NWnQ[FFwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MXHJR|UxRTF5LkmzNVIh|ryPMmXxV2FPT0WU
LAN-6NGP2[JBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M1ywSWlEPTB;MUiuO|U2PyEQvF2=NXHXenJKW0GQR1XS
A388MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MW\JR|UxRTF7LkOwOVkh|ryPMnW5V2FPT0WU
SK-NEP-1M3TXcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M3;wcWlEPTB;MkCuNlE{OiEQvF2=NEPPe2lUSU6JRWK=
TE-10MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MlW3TWM2OD1{MD61NlIyKM7:TR?=M1vm[nNCVkeHUh?=
HL-60MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MoOzTWM2OD1{MD65NFk6KM7:TR?=NY\OO2x1W0GQR1XS
MC116NETz[VdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NHLaPFlKSzVyPUKxMlczOjFizszNNHzUc4tUSU6JRWK=
SW962NGLFeXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M1f6VmlEPTB;MkGuO|kyPSEQvF2=MV3TRW5ITVJ?
NOMO-1NWDk[nRvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NHnuWolKSzVyPUKyMlY2PjRizszNM171RnNCVkeHUh?=
CTB-1MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NVLSUVM1UUN3ME2yNk45PjdzIN88US=>NIDiR5lUSU6JRWK=
MRK-nu-1NVnsRmRTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXLSVldXUUN3ME2yNk46ODd2IN88US=>MkOxV2FPT0WU
GR-STMmP1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NGn2cVhKSzVyPUKzMlc3KM7:TR?=NWX0NYdvW0GQR1XS
HHMXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NHjzNZNKSzVyPUK0MlAxOyEQvF2=NF;4WppUSU6JRWK=
NCI-H1963MlPWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MUXJR|UxRTJ2LkC3PFIh|ryPMYTTRW5ITVJ?
QIMR-WILMYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MojaTWM2OD1{ND64O|czKM7:TR?=M4D1[nNCVkeHUh?=
CGTH-W-1MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NFHSSGpKSzVyPUK1MlA4OjNizszNMkfpV2FPT0WU
LP-1NUPiUmhWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NV32OpdFUUN3ME2yOU43PTVzIN88US=>NXHReJlWW0GQR1XS
NCI-H748MlW5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M4Ll[mlEPTB;Mk[uOVE{PyEQvF2=MnjsV2FPT0WU
PF-382NGrmRldIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MYDJR|UxRTJ5LkKyNlMh|ryPNY\rXWVVW0GQR1XS
ATN-1NYThelR3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MmfOTWM2OD1{Nz6zO|MzKM7:TR?=MVjTRW5ITVJ?
L-540MnSxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M2PyRmlEPTB;MkeuOlQ2QSEQvF2=M1fKPHNCVkeHUh?=
LXF-289NGH1cXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MWfJR|UxRTJ5Lke1NVkh|ryPM{DKRnNCVkeHUh?=
LS-513NWrRV2hZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MlXBTWM2OD1{OD6xPFA4KM7:TR?=MVLTRW5ITVJ?
NCI-H1581MorqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NHyxOGFKSzVyPUOwMlM6PzZizszNMkjBV2FPT0WU
ES6NYHVTINiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NHTIO5lKSzVyPUOwMlY5QTlizszNNG\kO3lUSU6JRWK=
SW982NYDZWmlDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NVS3Tpd4UUN3ME2zNE45PTZ4IN88US=>NFLhSWlUSU6JRWK=
DOHH-2NV[wUIwxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M1\K[mlEPTB;M{GuOVg6OyEQvF2=NULnW|JxW0GQR1XS
DBNGnvNIlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NWPiOVRZUUN3ME2zN{46PDNzIN88US=>NVzvTWhoW0GQR1XS
MPP-89MoDDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MlPTTWM2OD1|ND6xO|U3KM7:TR?=MVfTRW5ITVJ?
LB831-BLCNV;OeFVtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NUTjTGFxUUN3ME2zOE42OTh2IN88US=>NFq5VG5USU6JRWK=
NB5Ml[0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MorPTWM2OD1|ND64OVM2KM7:TR?=NY\peGlNW0GQR1XS
GB-1MmDTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NFLP[INKSzVyPUO1MlA1PjlizszNNIKxfHdUSU6JRWK=
TE-15MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M1SzOGlEPTB;M{WuNlI{QCEQvF2=MXXTRW5ITVJ?
LC4-1Mn\GS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M4\5Z2lEPTB;M{WuN|g1PyEQvF2=MWXTRW5ITVJ?
NCI-H747NVzMZoZuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NGXXZYRKSzVyPUO2MlE{PjlizszNMX\TRW5ITVJ?
NTERA-S-cl-D1MmTkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M2q5PGlEPTB;M{iuO|M1PyEQvF2=MVLTRW5ITVJ?
SK-MM-2NWfVdphmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MUTJR|UxRTRyLkGxOFYh|ryPNYDjeVhsW0GQR1XS
TGWNUHHNGcyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NUHlco85UUN3ME20NU4xPTZ|IN88US=>MYDTRW5ITVJ?
ONS-76M2PnV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NXLLW48{UUN3ME20Nk41QDh|IN88US=>NHjsTYtUSU6JRWK=
CPC-NMoLGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NU\vTINiUUN3ME20Nk46QTdzIN88US=>MXvTRW5ITVJ?
ES4NFPRdZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MY\JR|UxRTR2LkSxOVMh|ryPMn3VV2FPT0WU
DaudiMljGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MV3JR|UxRTR3LkC4Nlch|ryPM2fwPHNCVkeHUh?=
MOLT-4NF7HcFRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MV;JR|UxRTR3LkC4OVMh|ryPMmO1V2FPT0WU
HT-144M2fGVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M1S2RWlEPTB;NE[uO|I3KM7:TR?=NEjWRm9USU6JRWK=
SW872NFG0NG5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MkLoTWM2OD12OD6xPVM{KM7:TR?=M1HucnNCVkeHUh?=
D-283MEDMkjpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NWi0d|ZzUUN3ME20PE4{PTR{IN88US=>MkDoV2FPT0WU
NCI-H2126NHzq[odIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M4rvcWlEPTB;NEiuPFQ4PiEQvF2=NWHJT5ZJW0GQR1XS
NCI-SNU-16NW[3XIh1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MV7JR|UxRTR7LkKxOFMh|ryPMVvTRW5ITVJ?
CESSMkHsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NXrHbFNxUUN3ME20PU42ODh6IN88US=>NUDGZW1iW0GQR1XS
A101DNHn1Z3RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M4DqWmlEPTB;NEmuPVc{PiEQvF2=MVjTRW5ITVJ?

... Click to View More Cell Line Experimental Data

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]
Features

Protocol(Only for Reference)

Kinase Assay: [1]

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 Assay: [1]

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.

Animal Study: [1]

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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Zou HY, et al. Cancer Res. 2007, 67(9), 4408-4417.

[2] Christensen JG, et al. Mol Cancer Ther. 2007, 6(12 Pt 1), 3314-3322.

view more

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-30)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02838420 Recruiting Anaplastic Lymphoma Kinase-positive Non-small Cell Lung Cancer Hoffmann-La Roche July 2016 Phase 3
NCT02836847 Recruiting Cholangiocarcinoma of the Extrahepatic Bile Duct|Gallbladder Cancer Shanghai Jiao Tong University School of Medicine|Xinhua H  ...more Shanghai Jiao Tong University School of Medicine|Xinhua Hospital, Shanghai Jiao Tong University School of Medicine|Ruijin Hospital|RenJi Hospital|Eastern Hepatobiliary Surgery Hospital|Huashan Hospital July 2016 Phase 2
NCT02767804 Recruiting Non-small Cell Lung Cancer Xcovery Holding Company, LLC June 2016 Phase 3
NCT02679170 Recruiting Non-Small Cell Lung Cancer Pfizer June 2016 --
NCT02761057 Recruiting Recurrent Renal Cell Carcinoma|Stage III Renal Cell Cancer|Stage IV Renal Cell Cancer|Type 1 Papillary Renal Cell Carcinoma|Type 2 Papillary Renal  ...more Recurrent Renal Cell Carcinoma|Stage III Renal Cell Cancer|Stage IV Renal Cell Cancer|Type 1 Papillary Renal Cell Carcinoma|Type 2 Papillary Renal Cell Carcinoma National Cancer Institute (NCI) April 2016 Phase 2

view more

Chemical Information

Download Crizotinib (PF-02341066) SDF
Molecular Weight (MW) 450.34
Formula

C21H22Cl2FN5O

CAS No. 877399-52-5
Storage 3 years -20℃powder
2 years -80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 9 mg/mL (19.98 mM)
Water <1 mg/mL
Ethanol <1 mg/mL
In vivo 5% DMSO+30% PEG 300+dd H2O 5mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* 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 Name 3-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine

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.

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.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related c-Met Products

  • NPS-1034

    NPS-1034 is a dual Met/Axl inhibitor with IC50 of 48 nM and 10.3 nM, respectively.

  • Erlotinib

    Erlotinib is an EGFR inhibitor with IC50 of 2 nM, >1000-fold more sensitive for EGFR than human c-Src or v-Abl.

  • R428 (BGB324)

    R428 (BGB324) is an inhibitor of Axl with IC50 of 14 nM, >100-fold selective for Axl versus Abl. Selectivty for Axl is also greater than Mer and Tyro3 (50-to-100- fold more selective) and InsR, EGFR, HER2, and PDGFRβ (100- fold more selective).

  • Foretinib (GSK1363089)

    Foretinib (GSK1363089) is an ATP-competitive inhibitor of HGFR and VEGFR, mostly for Met and KDR with IC50 of 0.4 nM and 0.9 nM in cell-free assays. Less potent against Ron, Flt-1/3/4, Kit, PDGFRα/β and Tie-2, and little activity to FGFR1 and EGFR. Phase 2.

  • Capmatinib (INCB28060)

    Capmatinib (INCB28060) is a novel, ATP-competitive inhibitor of c-MET with IC50 of 0.13 nM in a cell-free assay, inactive against RONβ, as well as EGFR and HER-3. Phase 1.

    Features:Inactive against RONβ, another member of the c-MET RTK family, as well as EGFR and HER-3 (members of the EGFR RTK family).

  • Tivantinib (ARQ 197)

    Tivantinib (ARQ 197) is the first non-ATP-competitive c-Met inhibitor with Ki of 0.355 μM in a cell-free assay, little activity to Ron, and no inhibition to EGFR, InsR, PDGFRα or FGFR1/4. Phase 3.

    Features:The first selective c-Met inhibitor to be advanced into human clinical trials.

  • PHA-665752

    PHA-665752 is a potent, selective and ATP-competitive c-Met inhibitor with IC50 of 9 nM in cell-free assays, >50-fold selectivity for c-Met than RTKs or STKs.

  • BMS-777607

    BMS-777607 is a Met-related inhibitor for c-Met, Axl, Ron and Tyro3 with IC50 of 3.9 nM, 1.1 nM, 1.8 nM and 4.3 nM in cell-free assays, 40-fold more selective for Met-related targets versus Lck, VEGFR-2, and TrkA/B, and more than 500-fold greater selectivity versus all other receptor and non receptor kinases. Phase 1/2.

    Features:A potent inhibitor of the Met family, and >40-fold selectivity vs. Lck, VEGFR2, and TrkA/B and >500-fold selective vs. other receptor and non-receptor kinases.

  • PF-04217903

    PF-04217903 is a selective ATP-competitive c-Met inhibitor with IC50 of 4.8 nM in A549 cell line, susceptible to oncogenic mutations (no activity to Y1230C mutant). Phase 1.

  • SU11274

    SU11274 is a selective Met inhibitor with IC50 of 10 nM in cell-free assays, no effects on PGDFRβ, EGFR or Tie2.

Recently Viewed Items

Tags: buy Crizotinib (PF-02341066) | Crizotinib (PF-02341066) supplier | purchase Crizotinib (PF-02341066) | Crizotinib (PF-02341066) cost | Crizotinib (PF-02341066) manufacturer | order Crizotinib (PF-02341066) | Crizotinib (PF-02341066) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Contact Us