Crizotinib (PF-02341066)

For research use only.

Licensed by Pfizer Catalog No.S1068

255 publications

Crizotinib (PF-02341066) Chemical Structure

Molecular Weight(MW): 450.34

Crizotinib (PF-02341066) is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM in cell-based assays, respectively. It is also a potent ROS1 inhibitor with Ki value less than 0.025 nM. Crizotinib induces autophagy through inhibition of the STAT3 pathway in multiple lung cancer cell lines.

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Selleck's Crizotinib (PF-02341066) has been cited by 255 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. Crizotinib induces autophagy through inhibition of the STAT3 pathway in multiple lung cancer cell lines.
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 MUPDfZRwfG:6aXOgRZN{[Xl? NUDLSnM6PDhiaB?= NF\ycGZFVVOR MlLTR5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmFHOyClZXzsd{BmgHC{ZYPzbY5oKEGOSzDGNVE4PExibYX0ZY51KGOxZYjwdoV{e2mwZzDFUWw1KHerdHigTWM2OCCxZjCwMlYzKM7:TR?= NH76fpczOTV5MkW4PS=>
BAF3 M{PlOWN6fG:2b4jpZ{BCe3OjeR?= NUTMOFZqPDhiaB?= NV\VS4RbTE2VTx?= NEPPXJREgXSxdH;4bYNqfHliYXfhbY5{fCCvb4Xz[UBDSUZ|IHPlcIx{KGW6cILld5NqdmdiQVzLJGwyOTl4TTDteZRidnRiY3;lfJBz\XO|aX7nJGVOVDRid3n0bEBKSzVyIH;mJFIvOiEQvF2= NH7TeFUzOTV5MkW4PS=>
BAF3 NHrsS4VEgXSxdH;4bYMhSXO|YYm= NXrQT5lWPDhiaB?= NVfXWWR[TE2VTx?= NFvZU5dEgXSxdH;4bYNqfHliYXfhbY5{fCCvb4Xz[UBDSUZ|IHPlcIx{KGW6cILld5NqdmdiRV3MOE1CVEtid3n0bEBKSzVyIH;mJFAvOjhizszN M4j5fFIyPTd{NUi5
Kelly NILNcHREgXSxdH;4bYMhSXO|YYm= NGPO[oRFVVOR MmOyR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gT4VtdHliY3XscJMh\XiycnXzd4lv\yCDTFugSlEyPzSOIH31eIFvfCC5aYToJGlEPTBib3[gNE41OiEQvF2= MorENlE2PzJ3OEm=
SH-SY5Y MnHNR5l1d3SxeHnjJGF{e2G7 NWDHc2M1TE2VTx?= NXHuR3hkS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hW0hvU2m1XUBk\WyuczDlfJBz\XO|aX7nJGFNUyCIMUG3OGwhdXW2YX70JJdqfGhiSVO1NEBw\iByLkWzJO69VQ>? NHL1fGgzOTV5MkW4PS=>
SMS-KCN NYnhVnVYS3m2b4TvfIlkKEG|c3H5 MWrEUXNQ MXvDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDTUXMuU0OQIHPlcIx{KGW6cILld5NqdmdiQVzLJHIyOjd3UTDteZRidnRid3n0bEBKSzVyIH;mJFAvQTFizszN NIjQNWEzOTV5MkW4PS=>
BAF3 M3jMe2N6fG:2b4jpZ{BCe3OjeR?= MXm0PEBp MoO3SG1UVw>? MX\DfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRWY{KGOnbHzzJIV5eHKnc4PpcochXGWuLVHMT{B4cXSqIFnDOVAhd2ZiMD6xPUDPxE1? M3TVNlIyPTd{NUi5
3T3 NFGxclZHfW6ldHnvckBCe3OjeR?= NVjNSHZkOSCq NYjpOZBtTE2VTx?= MVjJcohq[mm2aX;uJI9nKFKRTjDhd5Nme3OnZDDhd{Boem:5dHig[oFkfG:{LXnu[JVk\WRiYYX0c5Bpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOC5yODFOwG0> NH\ncFgzOThzMkSxOC=>
3T3-E MUHGeY5kfGmxbjDBd5NigQ>? Ml7sNUBp MkjVSG1UVw>? M33sUWlvcGmkaYTpc44hd2ZiVFnFNkBie3Onc4Pl[EBoem:5dHig[oFkfG:{LXnu[JVk\WRiYYX0c5Bpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOC52NEig{txO MnHUNlE5OTJ2MUS=
A549 NH;ON4VMcW6jc3WgRZN{[Xl? NHvkfXIyKGh? NYrNTGd[TE2VTx?= NXrZW5pkUW6qaXLpeIlwdiCxZjDoeY1idiC{ZXPvcYJqdmGwdDDjMW1GXCCtaX7hd4Uh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IHnubIljcXSrb36gc4YhUEeILXnu[JVk\WRiYYX0c5Bpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOC5yMEig{txO MYCyNVgyOjRzNB?=
BAF3-BCL MnW3SpVv[3Srb36gRZN{[Xl? NV;iUGZlOSCq MVXEUXNQ NIr6UlBKdmirYnn0bY9vKG:oIFHCUEBie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMT6xOVkh|ryP MnSwNlE5OTJ2MUS=
HEK293 NF;GT|RHfW6ldHnvckBCe3OjeR?= NUny[YZxOSCq NVLxWI0xTE2VTx?= Mnz6TY5pcWKrdHnvckBw\iCDWFygZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwMkm0JO69VQ>? MorCNlE5OTJ2MUS=
HEK293 MUjGeY5kfGmxbjDBd5NigQ>? NEG0e2oyKGh? M2S5U2ROW09? M1XoXGlvcGmkaYTpc44hd2ZiSWKgZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDJwOEi3JO69VQ>? Mkm4NlE5OTJ2MUS=
Jurkat MlzqSpVv[3Srb36gRZN{[Xl? MoDjNUBp MWfEUXNQ Ml7MTY5pcWKrdHnvckBw\iCOQ1ugZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDJwN{SxJO69VQ>? MXOyNVgyOjRzNB?=
KARPAS299 MnTtT4lv[XOnIFHzd4F6 MYmxJIg> M2LlPGROW09? NFfsZ2JKdmirYnn0bY9vKG:oIFHMT{Bie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6wNkDPxE1? MWCyNVgyOjRzNB?=
PAE NX7zVFM3TnWwY4Tpc44hSXO|YYm= MWGxJIg> MYXEUXNQ MYLJcohq[mm2aX;uJI9nKFSUS1KgZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwM{m5JO69VQ>? NXrtWW5kOjF6MUK0NVQ>
BAF3 NFzEPXlHfW6ldHnvckBCe3OjeR?= MVKyMVMh\A>? M{nOOWROW09? NFz1OIpKdmirYnn0bY9vKG:oIGTFUE1nfXOnZDDpcpN2dGmwIILlZ4VxfG:{IHX4dJJme3OnZDD3bZRpKEmFNUCgc4YhOS54NEOg{txO MnKyNlM4PDJ{NUK=
KARPAS299 MknTR5l1d3SxeHnjJGF{e2G7 NV;LclFbOi1|IHS= NX\D[G1lTE2VTx?= MoPGTWM2OD1yLkC2OFIh|ryP NWCy[25vOjN5NEKyOVI>
EBC1 NFj2SXhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4r1TlczKGh? MWnEUXNQ M3vJRWlEPTB;MD6wNlMh|ryP Mmj2NlM6QTN|Mki=
HCT116 MmjQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUm3NkBp NX\3T4xJTE2VTx?= MofzTWM2OD1zND64NkDPxE1? M2m4bVI{QTl|M{K4
MCF7 NYXRT5dyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXK3NkBp MmDuSG1UVw>? M2rxXWlEPTB;OT61PEDPxE1? NF72bpczOzl7M{OyPC=>
MDA-MB-231 M2\NbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVm3NkBp MonsSG1UVw>? MVrJR|UxRTFyLkig{txO NFrBPVIzOzl7M{OyPC=>
MKN45 M3fOfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4XuVlczKGh? M1jKW2ROW09? MmXCTWM2OD1yLkCxN{DPxE1? NYfZb2hTOjN7OUOzNlg>
NCI-H441 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV[3NkBp MkXISG1UVw>? NWXa[JE6UUN3ME2xO{4zPSEQvF2= NIX4WnMzOzl7M{OyPC=>
NCI-H661 NXPKXm1sT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn7OO|IhcA>? M1zuW2ROW09? Mm\GTWM2OD1zMT60O{DPxE1? NIO1[oYzOzl7M{OyPC=>
SK-MEL-28 NWPwdpczT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEHST4g4OiCq NH7icZRFVVOR MVPJR|UxRTFyLkm3JO69VQ>? NXPyOXUyOjN7OUOzNlg>
SKOV3 NFvTcYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXn1S|dSPzJiaB?= NXTscXcxTE2VTx?= NYHQUFgzUUN3ME2xNk45PSEQvF2= MVqyN|k6OzN{OB?=
SNU5 M2nDN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MofYO|IhcA>? NUnjVlNYTE2VTx?= MV7JR|UxRTBwMEG2JO69VQ>? NUjkc3diOjN7OUOzNlg>
NCI-H2228 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGDIOZI4OiCq MnzZSG1UVw>? MnzmTY5pcWKrdHnvckBw\iCDTFut[pV{cW:wIHTybZZmdiClZXzsJJBzd2yrZnXyZZRqd25id3n0bEBKSzVyIH;mJFAvOTF6IN88US=> NE\jZmQzPDR|MkmwPS=>
NCI-H3122 M1HVWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFmwb|Y4OiCq M4S4U2ROW09? MW\Jcohq[mm2aX;uJI9nKEGOSz3meZNqd25iZILpeoVvKGOnbHygdJJwdGmoZYLheIlwdiC5aYToJGlEPTBib3[gNE4yODhizszN Mn3zNlQ1OzJ7MEm=
NCI-H3122 NVTXfG8{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWW3NkBp M2\INmROW09? MoL0TY5pcWKrdHnvckBw\iCDTFut[pV{cW:wIHTybZZmdiClZXzsJJBzd2yrZnXyZZRqd25iaX6gbJVu[W5iTlPJMWg{OTJ{IHPlcIx{KGijcnLvdolv\yCDTFugS|EzPjmDIH31eIFvfCC5aYToJGlEPTBib3[gNE43OjNizszN NWnO[|BDOjR2M{K5NFk>
NCI-H3122 MnnqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFzqOVc4OiCq MYPEUXNQ NVnNeWVpUW6qaXLpeIlwdiCxZjDBUGsu\nW|aX;uJIRzcX[nbjDj[YxtKHC{b3zp[oVz[XSrb36gbY4hcHWvYX6gUmNKNUh|MUKyJINmdGy|IHjhdoJwemmwZzDBUGshVDFzOU\NJI12fGGwdDD3bZRpKEmFNUCgc4YhOC56M{ig{txO NFOyXFUzPDR|MkmwPS=>
NIH-3T3 MUjLbY5ie2ViQYPzZZk> NIDyfWsyKGh? MkDNSG1UVw>? M1S4[mlvcGmkaYTpc44hd2ZiaIXtZY4hf2muZDD0fZBmKEWPTESt[pV{\WRiQVzLJIV5eHKnc4Pl[EBie3Onc4Pl[EBieyCyaH;zdIhwenmuYYTl[EBCVEtibHX2[Ywhf2m2aDDJR|UxKG:oIECuNFgh|ryP NEfVSYwzPDR|MkmwPS=>
NIH-3T3 MnXrT4lv[XOnIFHzd4F6 M4fVW|EhcA>? M2K5fGROW09? MlHvTY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzDHNVI3QUFibYX0ZY51KGW6cILld5Nm\CCjc4Pld5Nm\CCjczDwbI9{eGixLVHMT{Bt\X[nbDD3bZRpKEmFNUCgc4YhOC54MEWg{txO M{TyT|I1PDN{OUC5
NIH-3T3 M3j3OGtqdmG|ZTDBd5NigQ>? MXOxJIg> M4f3WGROW09? Mm\4TY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzDTNVIxPllibYX0ZY51KGW6cILld5Nm\CCjc4Pld5Nm\CCjczDwbI9{eGixLVHMT{Bt\X[nbDD3bZRpKEmFNUCgc4YhOC54Mk[g{txO NHHGTHgzPDR|MkmwPS=>
NIH-3T3 MX;LbY5ie2ViQYPzZZk> Mlu4NUBp NF;5cppFVVOR MVTJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIFyxNVk3VSCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAxNjh2MzFOwG0> MnjFNlQ1OzJ7MEm=
NIH-3T3 M1TrSmtqdmG|ZTDBd5NigQ>? MVuxJIg> NYf1TXRyTE2VTx?= MonpTY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzDMNVE2OlJibYX0ZY51KGW6cILld5Nm\CCjc4Pld5Nm\CCjczDwbI9{eGixLVHMT{Bt\X[nbDD3bZRpKEmFNUCgc4YhOS5yMk[g{txO MoLSNlQ1OzJ7MEm=
BAF3 M1LnSWZ2dmO2aX;uJGF{e2G7 MnPjO|IhcA>? M{e4fWROW09? MmOzTY5pcWKrdHnvckBw\iCQUF2vRWxMKHS{YX7z[oVkfGWmIHHzd4V{e2WmIHHzJINmdGxiZ4Lve5RpKGmwaHnibZRqd25id3n0bEBKSzVyIH;mJFAvODVzIN88US=> NG\UXHQzPDR4OE[zNi=>
BAF3 MlvVR5l1d3SxeHnjJGF{e2G7 M2TXNFczKGh? NIrzZXJFVVOR NGHKcZRKSzVyPUCuPVgh|ryP MmnwNlQ1Pjh4M{K=
NIH-3T3 M1;SUmtqdmG|ZTDBd5NigQ>? M3\ReVEhcA>? MX3Jcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIF[xNVc1VCCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAxNjF4NTFOwG0> MYmyOFgyQTFzNh?=
NIH-3T3 NYTWeW5EU2mwYYPlJGF{e2G7 M3;SbFEhcA>? MUTJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIFOxNVU3YSCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAxNjR5ODFOwG0> MnvoNlQ5OTlzMU[=
NIH-3T3 MXPLbY5ie2ViQYPzZZk> MXKxJIg> MULJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIFexNlAzWiCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAyNjF2ODFOwG0> NITrdYEzPDhzOUGxOi=>
NIH-3T3 Mn;mT4lv[XOnIFHzd4F6 Mo[xNUBp MXfJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIEGxOVFVcW6|IH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDNwMEO5JO69VQ>? NHfHcFkzPDhzOUGxOi=>
KARPAS299 M1X6eWtqdmG|ZTDBd5NigQ>? MXG5NEBucW5? M{TQOGROW09? Ml7FTY5pcWKrdHnvckBw\iCQUF2t[pV{\WRiQVzLJJBpd3OyaH;yfYxifGmxbjDlfJBz\XO|ZXSge4l1cCCLQ{WwJI9nKDBwMUGg{txO MmfJNlQ6ODB5NUC=
MKN 45 M3nKNWtqdmG|ZTDBd5NigQ>? M13idFEhcA>? NHLhPINFVVOR MV7Jcohq[mm2aX;uJI9nKGNvTXX0JJBpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOC5yMjFOwG0> MofmNlQ6ODB5NUC=
A549 NXnsdYczS3m2b4TvfIlkKEG|c3H5 MoTwOFghcA>? M4GzUWROW09? NHvMPZZKSzVyIH;mJFQvODh2IN88US=> NW\yUYNIOjR7MEC4N|A>
NCI-H1975 NVzVfGE1S3m2b4TvfIlkKEG|c3H5 NEDWclI1QCCq NWq0endZTE2VTx?= NUjKR3M3UUN3MDDv[kA4NjV3MTFOwG0> MW[yOFkxODh|MB?=
NCI-H1993 NYThfpZ3S3m2b4TvfIlkKEG|c3H5 MVy0PEBp M1H4b2ROW09? NEWyT21KSzVyIH;mJFAvODZzIN88US=> MVeyOFkxODh|MB?=
NCI-H1993 NWjUOZhbSXCxdH;zbZMhSXO|YYm= NH;IfncyKM7:TR?= MYWyOEBp MWPEUXNQ MV7kc4V{KG6xdDDpcoR2[2ViYYDvdJRwe2m| MmDZNlQ6ODB6M{C=
NIH-3T3 MWPDfZRwfG:6aXOgRZN{[Xl? NYXwVnd4PDhiaB?= M2X0UmROW09? MoP0TWM2OCCxZjCwMlM3PCEQvF2= M4fEc|I1QTByOEOw
EBC1 M324N2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEHpR2s4OiCq MYrEUXNQ M4mxTmlEPTBib3[gNE4xODZ7IN88US=> MU[yOFkxODh|MR?=
KARPAS299 NGPjc|JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWS3NkBp MX\EUXNQ NFW1VW5KSzVyIH;mJFAvOiEQvF2= NXjZUGNlOjR7MEC4N|E>
NB1 NE\GOlJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1XF[WlEPTB;OUGuPVghdk1? NYLLboZYW0GQR1XS
NCI-SNU-5 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX\MeoxPUUN3ME2xNFUvPzVibl2= M4rlV3NCVkeHUh?=
SR NXzKWXdkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml\3TWM2OD1zMk[uN|Ehdk1? MnjjV2FPT0WU
SF539 M4e2V2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWq1c4YxUUN3ME2yNFQvOjRibl2= NIHQZnJUSU6JRWK=
SU-DHL-1 NF:xVVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVK3bpFbUUN3ME2zN|YvQDJibl2= Mn;sV2FPT0WU
SCC-3 MlGyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M37Gd2lEPTB;M{W2Mlc3KG6P NGH2eWFUSU6JRWK=
DEL NG\ndmNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXXXdGVVUUN3ME2zOlkvQSCwTR?= M{DlUHNCVkeHUh?=
CTV-1 NVTBbpM5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M17oO2lEPTB;NUm2MlQ5KG6P MmjEV2FPT0WU
EM-2 NYnVTWFCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3jUdmlEPTB;NkCxMlM1KG6P MY\TRW5ITVJ?
MHH-CALL-2 M2LIb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml70TWM2OD14OEKuOVchdk1? NV76T5hWW0GQR1XS
KM12 NUnoV|l3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkXGTWM2OD15ME[uPUBvVQ>? NX20[I9XW0GQR1XS
KINGS-1 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1PyTWlEPTB;N{S5Mlc2KG6P MYTTRW5ITVJ?
MEG-01 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXHJR|UxRTh3Nz62OkBvVQ>? M2T0W3NCVkeHUh?=
BV-173 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFnpT2dKSzVyPUGuNFU6QTdizszN M3j6fHNCVkeHUh?=
LAMA-84 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUfJR|UxRTFwM{iyPFIh|ryP NXHTTGU1W0GQR1XS
KARPAS-299 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEjpOoxKSzVyPUGuOFA5PjFizszN NYPLOGZxW0GQR1XS
K-562 Mk[xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEPZW|hKSzVyPUGuO|IzPjlizszN NHPtWGRUSU6JRWK=
SK-LMS-1 M1;4OGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF3JZ49KSzVyPUGuO|Y5PjdizszN MkKwV2FPT0WU
MOLT-16 Ml;nS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mnn4TWM2OD1zLkm1OVc2KM7:TR?= MmHRV2FPT0WU
CMK MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVvJR|UxRTFwOU[xOVkh|ryP M2HXVXNCVkeHUh?=
ST486 NF;SXVFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHzTO4pKSzVyPUKuOFMxPzNizszN MWjTRW5ITVJ?
CI-1 MmfLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWfP[XhmUUN3ME2yMlQ6PjV7IN88US=> MoL4V2FPT0WU
KP-N-RT-BM-1 M2LvSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnnvTWM2OD1{LkewNVIzKM7:TR?= MkXlV2FPT0WU
ALL-PO MnLXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmXBTWM2OD1|LkG4NlA4KM7:TR?= NIfmPHFUSU6JRWK=
KS-1 NF:0PYhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIXBNIZKSzVyPUOuNlEzOjVizszN M2f2OnNCVkeHUh?=
Becker M4PV[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mke2TWM2OD12LkKzPVMh|ryP NGXPdXZUSU6JRWK=
GDM-1 NV35b|hZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVnpZ2RbUUN3ME20MlI1PjF5IN88US=> M1X5O3NCVkeHUh?=
BC-1 M3S3XGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVHJR|UxRTRwNEmyO|ch|ryP M2DnbnNCVkeHUh?=
NB14 NIX4SopIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUXLVmZHUUN3ME20Mlg{PTJ2IN88US=> MWnTRW5ITVJ?
NOS-1 NWK1[lFFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4LqU2lEPTB;NT6zN|g4PCEQvF2= NUL2b4FVW0GQR1XS
MZ1-PC MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHe3SHJKSzVyPUWuPFIyPTFizszN M4PNT3NCVkeHUh?=
A498 NWXWNmpJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWTJR|UxRTZwMEi0O|Mh|ryP NFTRSZBUSU6JRWK=
EW-16 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1z0dGlEPTB;Nj6zO|c4OyEQvF2= NYiwfolVW0GQR1XS
NALM-6 Ml7lS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIryTI1KSzVyPU[uOlg{QDdizszN NX\Hb4h5W0GQR1XS
EB-3 NXjlZW5XT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3vkRmlEPTB;Nz6wO|I{OyEQvF2= NGXIVoNUSU6JRWK=
697 MmnlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGPsSHBKSzVyPUmuNlQ{OjlizszN MlXlV2FPT0WU
Ramos-2G6-4C10 NITFNG9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn3RTWM2OD17LkW5PFQzKM7:TR?= MlXLV2FPT0WU
KNS-81-FD M4PCe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHflZWJKSzVyPUmuOlk3PTNizszN Mk\TV2FPT0WU
HUTU-80 M2fD[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUHJR|UxRTlwN{S2OFIh|ryP MWrTRW5ITVJ?
LS-411N MmfmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEC1NIJKSzVyPUGwMlA2PjdizszN MmXlV2FPT0WU
RPMI-8402 NVHHNI1xT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NED5[mlKSzVyPUGwMlEyPiEQvF2= NYDEOlRIW0GQR1XS
KU812 NIrVfpZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXHHb2E4UUN3ME2xNE4zQTlzIN88US=> MUXTRW5ITVJ?
EW-1 NYrXVFdRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M325UWlEPTB;MUCuOFQzPSEQvF2= NFS1UI9USU6JRWK=
HC-1 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH3HSZVKSzVyPUGwMlQ5PDRizszN NFLJd|BUSU6JRWK=
NB69 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUjjUGtHUUN3ME2xNE42ODR|IN88US=> NU[4UmhSW0GQR1XS
MFH-ino MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2TyUmlEPTB;MUCuPFMxOyEQvF2= NH;wfG1USU6JRWK=
CCRF-CEM M4q2[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV\rUINUUUN3ME2xNU42QTdizszN M17HPXNCVkeHUh?=
SK-N-DZ NES2VZRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXnJR|UxRTF{LkC0N|Yh|ryP MlG2V2FPT0WU
NCI-H720 NXXRRpdPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXXxN|ZoUUN3ME2xNk4yPzB3IN88US=> M1\JfXNCVkeHUh?=
HCC1187 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIrQWplKSzVyPUGyMlIxPDFizszN NXjjT2tXW0GQR1XS
IST-SL2 M4HBSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NITvZohKSzVyPUGyMlQ5PzJizszN NXnkdHN{W0GQR1XS
KE-37 NHO3UnpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUjYS|hEUUN3ME2xNk44QTZ4IN88US=> NYTmSYtJW0GQR1XS
HCC1599 M17qc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MU\JR|UxRTF{LkmwOlkh|ryP NHe4c3NUSU6JRWK=
A4-Fuk NWXQRYppT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYnDPWtmUUN3ME2xNk46PTh4IN88US=> NFXJSnNUSU6JRWK=
NKM-1 NXT6R|B7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MU\JR|UxRTF|LkK5NlUh|ryP M2m2W3NCVkeHUh?=
BE-13 M1;KNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmDKTWM2OD1zMz63PVg6KM7:TR?= MXLTRW5ITVJ?
MV-4-11 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGrzXY1KSzVyPUG0MlA{OjRizszN MXfTRW5ITVJ?
OPM-2 NXWwXnR{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGrrc2ZKSzVyPUG0MlQxQDVizszN NIXyboRUSU6JRWK=
KARPAS-422 MnLqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4X0dWlEPTB;MUSuOVEzPiEQvF2= Mkj1V2FPT0WU
RPMI-8226 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFXtNYhKSzVyPUG0Mlg6OTVizszN MoXCV2FPT0WU
KARPAS-45 MnjRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3:1RmlEPTB;MUWuO|cyPiEQvF2= MXLTRW5ITVJ?
SK-PN-DW NW\sOWpUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWfNemdEUUN3ME2xOU45PjNzIN88US=> NX3BcFhOW0GQR1XS
LC-2 M3LnS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFrVfFlKSzVyPUG2MlE2ODZizszN NIHFWWpUSU6JRWK=
NCI-H1648 NWTUboppT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVvJR|UxRTF4LkK1OEDPxE1? MYnTRW5ITVJ?
RL95-2 NY\kTG06T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXnJR|UxRTF4LkO5O|gh|ryP MY\TRW5ITVJ?
KNS-42 M2HzVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXjJR|UxRTF4LkeyO|Qh|ryP NF3WNGZUSU6JRWK=
RPMI-6666 NX;zflM6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3HQ[mlEPTB;MU[uPVIyOSEQvF2= NGPxbHJUSU6JRWK=
SIG-M5 NYTPeWtWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXvJR|UxRTF5LkG5NFMh|ryP Mn;YV2FPT0WU
VA-ES-BJ NE\LcoZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlHHTWM2OD1zNz63OFUyKM7:TR?= M4\BPHNCVkeHUh?=
MONO-MAC-6 NX7YO4hVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYK2[phQUUN3ME2xO{46OzF{IN88US=> Mn\BV2FPT0WU
LAN-6 M4K5Vmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGDHXXZKSzVyPUG4Mlc2PTdizszN NWWwTGZXW0GQR1XS
A388 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1jtcGlEPTB;MUmuN|A2QSEQvF2= NFfLRYRUSU6JRWK=
SK-NEP-1 NFTQfI1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mm\oTWM2OD1{MD6yNVMzKM7:TR?= NV\KOGxOW0GQR1XS
TE-10 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkjFTWM2OD1{MD61NlIyKM7:TR?= MX;TRW5ITVJ?
HL-60 NVjPUWJTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NInPWXNKSzVyPUKwMlkxQTlizszN MmP4V2FPT0WU
MC116 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn[3TWM2OD1{MT63NlIyKM7:TR?= NFjwd5hUSU6JRWK=
SW962 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4HuUGlEPTB;MkGuO|kyPSEQvF2= M{XOSXNCVkeHUh?=
NOMO-1 M4e4PWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NITp[pVKSzVyPUKyMlY2PjRizszN M33ZUnNCVkeHUh?=
CTB-1 NHTUfXRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmfVTWM2OD1{Mj64OlcyKM7:TR?= NUG3eWJNW0GQR1XS
MRK-nu-1 NVjEPZpUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXHLTZo4UUN3ME2yNk46ODd2IN88US=> MnTDV2FPT0WU
GR-ST NFT5fnlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mm\UTWM2OD1{Mz63OkDPxE1? M3HzdXNCVkeHUh?=
HH MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2C5WGlEPTB;MkSuNFA{KM7:TR?= MYPTRW5ITVJ?
NCI-H1963 NVviPZhtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYrJR|UxRTJ2LkC3PFIh|ryP NHS0OI9USU6JRWK=
QIMR-WIL M{\iS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYLxXnJ1UUN3ME2yOE45Pzd{IN88US=> M4SwWHNCVkeHUh?=
CGTH-W-1 M{GwdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVzJR|UxRTJ3LkC3NlMh|ryP NVLRW25ZW0GQR1XS
LP-1 NFjtcJpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH3NWJVKSzVyPUK1MlY2PTFizszN M2j5dHNCVkeHUh?=
NCI-H748 M1nTdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH61TGFKSzVyPUK2MlUyOzdizszN NUPhRXlIW0GQR1XS
PF-382 NYDySXUxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M13COmlEPTB;MkeuNlIzOyEQvF2= MXfTRW5ITVJ?
ATN-1 NYS2b5YxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVy2TVFqUUN3ME2yO{4{PzN{IN88US=> M4Ts[nNCVkeHUh?=
L-540 NGfNbXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVvJR|UxRTJ5Lk[0OVkh|ryP MVrTRW5ITVJ?
LXF-289 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoL5TWM2OD1{Nz63OVE6KM7:TR?= NWLSOoc3W0GQR1XS
LS-513 M2n3Rmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEL3WG9KSzVyPUK4MlE5ODdizszN M2nyb3NCVkeHUh?=
NCI-H1581 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M13le2lEPTB;M{CuN|k4PiEQvF2= M4rpXHNCVkeHUh?=
ES6 NV6we|VtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHfsWFFKSzVyPUOwMlY5QTlizszN MUnTRW5ITVJ?
SW982 NUXzN4NiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF;LZ5pKSzVyPUOwMlg2PjZizszN NUPIe5E4W0GQR1XS
DOHH-2 NIC5R4NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mmf3TWM2OD1|MT61PFk{KM7:TR?= NWnJN|lsW0GQR1XS
DB MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVPJR|UxRTN|Lkm0N|Eh|ryP MojuV2FPT0WU
MPP-89 M{TNNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVn6fVVoUUN3ME2zOE4yPzV4IN88US=> MUjTRW5ITVJ?
LB831-BLC M2jwcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWfJR|UxRTN2LkWxPFQh|ryP NWHmVlhGW0GQR1XS
NB5 M2XLTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUf6c4FGUUN3ME2zOE45PTN3IN88US=> NYr3TpN3W0GQR1XS
GB-1 NHXGXYRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGHhWIFKSzVyPUO1MlA1PjlizszN MX7TRW5ITVJ?
TE-15 M{XWZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXvJR|UxRTN3LkKyN|gh|ryP MmXoV2FPT0WU
LC4-1 MoLaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmTOTWM2OD1|NT6zPFQ4KM7:TR?= MorxV2FPT0WU
NCI-H747 NWnNVVkzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4XCV2lEPTB;M{[uNVM3QSEQvF2= NIX3RopUSU6JRWK=
NTERA-S-cl-D1 MmXzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUjrSo1jUUN3ME2zPE44OzR5IN88US=> M4S2bXNCVkeHUh?=
SK-MM-2 M{nnOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3TCemlEPTB;NECuNVE1PiEQvF2= MWLTRW5ITVJ?
TGW NGPSNGlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXv2S41yUUN3ME20NU4xPTZ|IN88US=> NV;oWmxvW0GQR1XS
ONS-76 MoK4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoHtTWM2OD12Mj60PFg{KM7:TR?= M4Hje3NCVkeHUh?=
CPC-N NHjOdGFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHH2WZZKSzVyPUSyMlk6PzFizszN MYLTRW5ITVJ?
ES4 MlH4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVXJR|UxRTR2LkSxOVMh|ryP MW\TRW5ITVJ?
Daudi NHXXbXJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1LGcWlEPTB;NEWuNFgzPyEQvF2= MoTVV2FPT0WU
MOLT-4 M{nkWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX;JR|UxRTR3LkC4OVMh|ryP MUDTRW5ITVJ?
HT-144 M3TaOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3njZ2lEPTB;NE[uO|I3KM7:TR?= NFrQZZVUSU6JRWK=
SW872 Mnv6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVX4[4J4UUN3ME20PE4yQTN|IN88US=> MlHUV2FPT0WU
D-283MED NYe1WGhPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH;rZ3lKSzVyPUS4MlM2PDJizszN M36wdnNCVkeHUh?=
NCI-H2126 NWm3W3A2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkLxTWM2OD12OD64OFc3KM7:TR?= NHLtTHJUSU6JRWK=
NCI-SNU-16 NX:5RVVCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGXyOWRKSzVyPUS5MlIyPDNizszN M2LITXNCVkeHUh?=
CESS NYHPU|RVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXrJR|UxRTR7LkWwPFgh|ryP M3vQUHNCVkeHUh?=
A101D NVGx[o1LT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWrVWZdVUUN3ME20PU46PzN4IN88US=> NHv5bm9USU6JRWK=

... 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
  • Dosages: 12.5 mg/kg/day, 25 mg/kg/day, and 50 mg/kg/day
  • Administration: Administered via p.o.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 9 mg/mL (19.98 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
5% DMSO+30% PEG 300+dd H2O
For best results, use promptly after mixing.
5mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 450.34
Formula

C21H22Cl2FN5O

CAS No. 877399-52-5
Storage powder
in solvent
Synonyms N/A
Smiles CC(OC1=C(N)N=CC(=C1)C2=C[N](N=C2)C3CCNCC3)C4=C(Cl)C=CC(=C4Cl)F

In vivo Formulation Calculator (Clear solution)

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Step 2: Enter the in vivo formulation (Different batches have different solubility ratios, please contact Selleck to provide you with the correct ratio)
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Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04148066 Recruiting Diagnostic Test: ctDNA blood sample Carcinoma Non-Small-Cell Lung The Netherlands Cancer Institute|Roche Pharma AG July 17 2019 Phase 2
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 Unknown status 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

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