Crizotinib (PF-02341066)

For research use only.

Licensed by Pfizer Catalog No.S1068

285 publications

Crizotinib (PF-02341066) Chemical Structure

CAS No. 877399-52-5

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 285 publications

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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 NGDXVXBEgXSxdH;4bYMhSXO|YYm= NX\V[GlkPDhiaB?= NIH5SIRFVVOR NYrRWHFxS3m2b4TvfIlkcXS7IHHnZYlve3RibX;1d4UhSkGIMzDj[YxteyCneIDy[ZN{cW6pIFHMT{BHOTF5NFygcZV1[W62IHPv[ZhxemW|c3nu[{BGVUx2IIfpeIghUUN3MDDv[kAxNjZ{IN88US=> NYLz[GpoOjF3N{K1PFk>
BAF3 NHm0Z4dEgXSxdH;4bYMhSXO|YYm= M4e3flQ5KGh? M3PpO2ROW09? M3LFc2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KG2xdYPlJGJCTjNiY3XscJMh\XiycnXzd4lv\yCDTFugUFEyQT[PIH31eIFvfCClb3X4dJJme3OrbnegSW1NPCC5aYToJGlEPTBib3[gNk4zKM7:TR?= MYeyNVU4OjV6OR?=
BAF3 NFnnem1EgXSxdH;4bYMhSXO|YYm= MWO0PEBp MV7EUXNQ MYLDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRWY{KGOnbHzzJIV5eHKnc4PpcochTU2OND3BUGshf2m2aDDJR|UxKG:oIECuNlgh|ryP MmnMNlE2PzJ3OEm=
Kelly MUPDfZRwfG:6aXOgRZN{[Xl? MonaSG1UVw>? MYnDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDL[YxtgSClZXzsd{BmgHC{ZYPzbY5oKEGOSzDGNVE4PExibYX0ZY51KHerdHigTWM2OCCxZjCwMlQzKM7:TR?= MUmyNVU4OjV6OR?=
SH-SY5Y M2HUV2N6fG:2b4jpZ{BCe3OjeR?= M2XMO2ROW09? NWqwdHh3S3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hW0hvU2m1XUBk\WyuczDlfJBz\XO|aX7nJGFNUyCIMUG3OGwhdXW2YX70JJdqfGhiSVO1NEBw\iByLkWzJO69VQ>? Mlm3NlE2PzJ3OEm=
SMS-KCN M{DhO2N6fG:2b4jpZ{BCe3OjeR?= NXzZeo9lTE2VTx?= MmX6R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV21UNUuFTjDj[YxteyCneIDy[ZN{cW6pIFHMT{BTOTJ5NWGgcZV1[W62IIfpeIghUUN3MDDv[kAxNjlzIN88US=> M{P0TlIyPTd{NUi5
BAF3 MWDDfZRwfG:6aXOgRZN{[Xl? MVy0PEBp NICx[mpFVVOR MYDDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRWY{KGOnbHzzJIV5eHKnc4PpcochXGWuLVHMT{B4cXSqIFnDOVAhd2ZiMD6xPUDPxE1? MnT4NlE2PzJ3OEm=
3T3 NYLXfo95TnWwY4Tpc44hSXO|YYm= M{jLSFEhcA>? NWL1PYlbTE2VTx?= Mlm2TY5pcWKrdHnvckBw\iCUT16gZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwMEig{txO MW[yNVgyOjRzNB?=
3T3-E MnP1SpVv[3Srb36gRZN{[Xl? MnTINUBp MUnEUXNQ Ml[4TY5pcWKrdHnvckBw\iCWSVWyJIF{e2W|c3XkJIdzd3e2aDDmZYN1d3JvaX7keYNm\CCjdYTvdIhwe3Cqb4L5cIF1cW:wIIfpeIghUUN3MDDv[kAxNjR2ODFOwG0> M4f1WVIyQDF{NEG0
A549 NVfXc3lyU2mwYYPlJGF{e2G7 M3f3Z|EhcA>? MlexSG1UVw>? M2HseGlvcGmkaYTpc44hd2ZiaIXtZY4hemWlb33ibY5idnRiYz3NSXQhc2mwYYPlJIV5eHKnc4Pl[EBie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGhITi2rbnT1Z4VlKGG3dH;wbI9{eGixconsZZRqd25id3n0bEBKSzVyIH;mJFAvODB6IN88US=> M1PXUlIyQDF{NEG0
BAF3-BCL MUfGeY5kfGmxbjDBd5NigQ>? MlLqNUBp MWrEUXNQ NGLtXodKdmirYnn0bY9vKG:oIFHCUEBie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMT6xOVkh|ryP MmXwNlE5OTJ2MUS=
HEK293 M2W4fGZ2dmO2aX;uJGF{e2G7 MXOxJIg> MnXiSG1UVw>? Mn;0TY5pcWKrdHnvckBw\iCDWFygZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwMkm0JO69VQ>? NXO0[45{OjF6MUK0NVQ>
HEK293 Ml\aSpVv[3Srb36gRZN{[Xl? Mom2NUBp M37oXmROW09? NHqzPW9KdmirYnn0bY9vKG:oIFnSJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iB{Lki4O{DPxE1? NInvZogzOThzMkSxOC=>
Jurkat MWTGeY5kfGmxbjDBd5NigQ>? M3\6bFEhcA>? M2XlfWROW09? NUnwblFpUW6qaXLpeIlwdiCxZjDMR2sh[XO|ZYPz[YQh[XNiZ4Lve5RpKG[jY4Tvdk1qdmS3Y3XkJIF2fG:yaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIEKuO|QyKM7:TR?= M1vsUVIyQDF{NEG0
KARPAS299 NFrMd5BMcW6jc3WgRZN{[Xl? NFLTW2cyKGh? MlmzSG1UVw>? MkezTY5pcWKrdHnvckBw\iCDTFugZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwMEKg{txO MV6yNVgyOjRzNB?=
PAE M{\lZ2Z2dmO2aX;uJGF{e2G7 M4rSZ|EhcA>? Ml\3SG1UVw>? NWnwe25bUW6qaXLpeIlwdiCxZjDUVmtDKGG|c3Xzd4VlKGG|IHfyc5d1cCCoYXP0c5IucW6mdXPl[EBifXSxcHjvd5Bpd3K7bHH0bY9vKHerdHigTWM2OCCxZjCwMlM6QSEQvF2= NYfZU4d4OjF6MUK0NVQ>
BAF3 NWm5OoZSTnWwY4Tpc44hSXO|YYm= NF7Zb5gzNTNiZB?= Mn\FSG1UVw>? M3\5NWlvcGmkaYTpc44hd2ZiVFXMMYZ2e2WmIHnud5VtcW5icnXj[ZB1d3JiZYjwdoV{e2WmIIfpeIghUUN3MDDv[kAyNjZ2MzFOwG0> NIjleWIzOzd2MkK1Ni=>
KARPAS299 NH[2eZdEgXSxdH;4bYMhSXO|YYm= NYLUW3J3Oi1|IHS= MmDPSG1UVw>? MVLJR|UxRTBwME[0NkDPxE1? M4LCOFI{PzR{MkWy
EBC1 NIrufW5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEK3Z2w4OiCq NHHGTG5FVVOR MUDJR|UxRTBwMEKzJO69VQ>? MYqyN|k6OzN{OB?=
HCT116 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1TMO|czKGh? MlLRSG1UVw>? MnrVTWM2OD1zND64NkDPxE1? NX7YeWpFOjN7OUOzNlg>
MCF7 NHvMeIpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWm3NkBp M{HRZ2ROW09? NVLYeo04UUN3ME25MlU5KM7:TR?= NHf3[4MzOzl7M{OyPC=>
MDA-MB-231 NYHmNHpFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYK3NkBp MmnQSG1UVw>? M175bWlEPTB;MUCuPEDPxE1? NIH5RlUzOzl7M{OyPC=>
MKN45 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1HK[lczKGh? M3;Zb2ROW09? NGH4RnVKSzVyPUCuNFE{KM7:TR?= MnzaNlM6QTN|Mki=
NCI-H441 NIT4RpRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2HpZVczKGh? M3L5R2ROW09? NVLvPG1kUUN3ME2xO{4zPSEQvF2= M4\vU|I{QTl|M{K4
NCI-H661 NF\YWVhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M122TFczKGh? NFzHW5VFVVOR MXnJR|UxRTFzLkS3JO69VQ>? M1T2VVI{QTl|M{K4
SK-MEL-28 M3LqS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVq3NkBp M{Dke2ROW09? M1;jNWlEPTB;MUCuPVch|ryP NGXkWFkzOzl7M{OyPC=>
SKOV3 Ml7KS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmHOO|IhcA>? NIXPdJlFVVOR MkPBTWM2OD1zMj64OUDPxE1? MXqyN|k6OzN{OB?=
SNU5 NFnqRXNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmrOO|IhcA>? NF3KeYpFVVOR NX\ubVZrUUN3ME2wMlAyPiEQvF2= NHXsZVMzOzl7M{OyPC=>
NCI-H2228 NUXQPYdKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWHpdJpZPzJiaB?= NEnjOoZFVVOR MVnJcohq[mm2aX;uJI9nKEGOSz3meZNqd25iZILpeoVvKGOnbHygdJJwdGmoZYLheIlwdiC5aYToJGlEPTBib3[gNE4yOThizszN NFX2SnYzPDR|MkmwPS=>
NCI-H3122 M2\PXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIrzOG44OiCq M2O0NWROW09? MWXJcohq[mm2aX;uJI9nKEGOSz3meZNqd25iZILpeoVvKGOnbHygdJJwdGmoZYLheIlwdiC5aYToJGlEPTBib3[gNE4yODhizszN MkX4NlQ1OzJ7MEm=
NCI-H3122 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlLkO|IhcA>? MkPtSG1UVw>? NVPwfIdxUW6qaXLpeIlwdiCxZjDBUGsu\nW|aX;uJIRzcX[nbjDj[YxtKHC{b3zp[oVz[XSrb36gbY4hcHWvYX6gUmNKNUh|MUKyJINmdGy|IHjhdoJwemmwZzDBUGshTzF{NknBJI12fGGwdDD3bZRpKEmFNUCgc4YhOC54MkOg{txO NXPUXm1iOjR2M{K5NFk>
NCI-H3122 NFftd29Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFH6SZg4OiCq NUiwTWExTE2VTx?= NH70NYxKdmirYnn0bY9vKG:oIFHMT{1nfXOrb36g[JJqfmWwIHPlcIwheHKxbHnm[ZJifGmxbjDpckBpfW2jbjDOR2kuUDNzMkKgZ4VtdHNiaHHyZo9zcW6pIFHMT{BNOTF7Nl2gcZV1[W62IIfpeIghUUN3MDDv[kAxNjh|ODFOwG0> NEnyeWQzPDR|MkmwPS=>
NIH-3T3 Mn73T4lv[XOnIFHzd4F6 NG\LWYsyKGh? Ml;ZSG1UVw>? M1vDOWlvcGmkaYTpc44hd2ZiaIXtZY4hf2muZDD0fZBmKEWPTESt[pV{\WRiQVzLJIV5eHKnc4Pl[EBie3Onc4Pl[EBieyCyaH;zdIhwenmuYYTl[EBCVEtibHX2[Ywhf2m2aDDJR|UxKG:oIECuNFgh|ryP NIK5fZEzPDR|MkmwPS=>
NIH-3T3 NIm4[JpMcW6jc3WgRZN{[Xl? NWrxc5hqOSCq M33wZWROW09? NFTmXY1KdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJGcyOjZ7QTDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLk[wOUDPxE1? NITMfJgzPDR|MkmwPS=>
NIH-3T3 Mle4T4lv[XOnIFHzd4F6 MV2xJIg> NIPCUlZFVVOR NGHIdHBKdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJHMyOjB4WTDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLk[yOkDPxE1? MVSyOFQ{OjlyOR?=
NIH-3T3 M{Szb2tqdmG|ZTDBd5NigQ>? MX[xJIg> MoK1SG1UVw>? Mn6wTY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzDMNVE6Pk1ibYX0ZY51KGW6cILld5Nm\CCjc4Pld5Nm\CCjczDwbI9{eGixLVHMT{Bt\X[nbDD3bZRpKEmFNUCgc4YhOC56NEOg{txO NUnEeoZYOjR2M{K5NFk>
NIH-3T3 MUDLbY5ie2ViQYPzZZk> Moq4NUBp Mn\SSG1UVw>? MmLrTY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzDMNVE2OlJibYX0ZY51KGW6cILld5Nm\CCjc4Pld5Nm\CCjczDwbI9{eGixLVHMT{Bt\X[nbDD3bZRpKEmFNUCgc4YhOS5yMk[g{txO M1\wV|I1PDN{OUC5
BAF3 M4XqR2Z2dmO2aX;uJGF{e2G7 M{fjc|czKGh? M2PadWROW09? Mk\jTY5pcWKrdHnvckBw\iCQUF2vRWxMKHS{YX7z[oVkfGWmIHHzd4V{e2WmIHHzJINmdGxiZ4Lve5RpKGmwaHnibZRqd25id3n0bEBKSzVyIH;mJFAvODVzIN88US=> NUTHNWdoOjR2Nki2N|I>
BAF3 MmToR5l1d3SxeHnjJGF{e2G7 MnznO|IhcA>? NGf1TJpFVVOR M4jUZWlEPTB;MD65PEDPxE1? MYGyOFQ3QDZ|Mh?=
NIH-3T3 M1jMNWtqdmG|ZTDBd5NigQ>? NIPrPXIyKGh? NFXrWZdKdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJGYyOTd2TDDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLkG2OUDPxE1? MUmyOFgyQTFzNh?=
NIH-3T3 M4LSfGtqdmG|ZTDBd5NigQ>? MXexJIg> MVzJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIFOxNVU3YSCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAxNjR5ODFOwG0> MUmyOFgyQTFzNh?=
NIH-3T3 MorVT4lv[XOnIFHzd4F6 M4S4OVEhcA>? NV7KOWdiUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BIOTJyMmKgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMT6xOFgh|ryP MW[yOFgyQTFzNh?=
NIH-3T3 MX7LbY5ie2ViQYPzZZk> MUGxJIg> MlTkTY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzCxNVUyXGmwczDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iB|LkCzPUDPxE1? MlTENlQ5OTlzMU[=
KARPAS299 NVe0NIxZU2mwYYPlJGF{e2G7 NWPFfGJ1QTBibXnu NX;IcHJuTE2VTx?= MUTJcohq[mm2aX;uJI9nKE6STT3meZNm\CCDTFugdIhwe3Cqb4L5cIF1cW:wIHX4dJJme3OnZDD3bZRpKEmFNUCgc4YhOC5zMTFOwG0> MWGyOFkxODd3MB?=
MKN 45 Mo[wT4lv[XOnIFHzd4F6 M4Kzb|EhcA>? MXXEUXNQ NYfMPYU{UW6qaXLpeIlwdiCxZjDjMW1mfCCyaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIECuNFIh|ryP Mn;1NlQ6ODB5NUC=
A549 MoLXR5l1d3SxeHnjJGF{e2G7 MkHQOFghcA>? NX\ndY8yTE2VTx?= MnnnTWM2OCCxZjC0MlA5PCEQvF2= NWj6XYsxOjR7MEC4N|A>
NCI-H1975 MoH1R5l1d3SxeHnjJGF{e2G7 M{T6[VQ5KGh? MU\EUXNQ MUPJR|UxKG:oIEeuOVUyKM7:TR?= NGq0UpUzPDlyMEizNC=>
NCI-H1993 M{TPW2N6fG:2b4jpZ{BCe3OjeR?= NELrbJI1QCCq NY\HbI5nTE2VTx?= MUDJR|UxKG:oIECuNFYyKM7:TR?= M3znTlI1QTByOEOw
NCI-H1993 MWDBdI91d3OrczDBd5NigQ>? MWqxJO69VQ>? M4HGWFI1KGh? MUHEUXNQ NEnB[nBld2W|IH7veEBqdmS3Y3WgZZBweHSxc3nz MYmyOFkxODh|MB?=
NIH-3T3 MXPDfZRwfG:6aXOgRZN{[Xl? Mnf5OFghcA>? Ml;OSG1UVw>? MWnJR|UxKG:oIECuN|Y1KM7:TR?= MmTPNlQ6ODB6M{C=
EBC1 NEPWO|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV7NVpFOPzJiaB?= NWPkd4F1TE2VTx?= MXzJR|UxKG:oIECuNFA3QSEQvF2= NG\SOZYzPDlyMEizNS=>
KARPAS299 NYXZNVhXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXq3NkBp M4rJSGROW09? M1:2N2lEPTBib3[gNE4zKM7:TR?= M2LhSVI1QTByOEOx
NB1 NWjU[5VET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEL3NoxKSzVyPUmxMlk5KG6P M2nEdnNCVkeHUh?=
NCI-SNU-5 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnrkTWM2OD1zMEWuO|Uhdk1? NILtfHhUSU6JRWK=
SR NX;F[Zd1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEHjOHlKSzVyPUGyOk4{OSCwTR?= NYe4WXpKW0GQR1XS
SF539 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUnoXoZ6UUN3ME2yNFQvOjRibl2= MlHCV2FPT0WU
SU-DHL-1 MmjRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEDSeHRKSzVyPUOzOk45OiCwTR?= MoKyV2FPT0WU
SCC-3 MoXXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn;pTWM2OD1|NU[uO|Yhdk1? M2LLdHNCVkeHUh?=
DEL NYHzdYo4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4PlOmlEPTB;M{[5Mlkhdk1? MW\TRW5ITVJ?
CTV-1 NVixZ5ZLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVjJR|UxRTV7Nj60PEBvVQ>? M1PUd3NCVkeHUh?=
EM-2 M3ThUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVq0SoM2UUN3ME22NFEvOzRibl2= Mk\RV2FPT0WU
MHH-CALL-2 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXnJR|UxRTZ6Mj61O{BvVQ>? MkHYV2FPT0WU
KM12 MoO3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWnJR|UxRTdyNj65JI5O M{nhOHNCVkeHUh?=
KINGS-1 NID6[GlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoHwTWM2OD15NEmuO|Uhdk1? NGDPNIpUSU6JRWK=
MEG-01 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYPJR|UxRTh3Nz62OkBvVQ>? M4TPXnNCVkeHUh?=
BV-173 NGe5T3BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVrVNWdIUUN3ME2xMlA2QTl5IN88US=> NGHTV5VUSU6JRWK=
LAMA-84 NWPOeIVvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUHvOY8zUUN3ME2xMlM5Ojh{IN88US=> MoTuV2FPT0WU
KARPAS-299 M1HCe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmnETWM2OD1zLkSwPFYyKM7:TR?= MXHTRW5ITVJ?
K-562 MlvZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2HLU2lEPTB;MT63NlI3QSEQvF2= MWLTRW5ITVJ?
SK-LMS-1 M37vSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUHJR|UxRTFwN{[4Olch|ryP M3z6SXNCVkeHUh?=
MOLT-16 M4LaWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2rCcGlEPTB;MT65OVU4PSEQvF2= M1G5SHNCVkeHUh?=
CMK NXrVOXZbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1LMSmlEPTB;MT65OlE2QSEQvF2= MkDPV2FPT0WU
ST486 MmS4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHfXOpBKSzVyPUKuOFMxPzNizszN MnqyV2FPT0WU
CI-1 M1rRSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUD2b2pWUUN3ME2yMlQ6PjV7IN88US=> MnnJV2FPT0WU
KP-N-RT-BM-1 M2jET2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGfrXY9KSzVyPUKuO|AyOjJizszN MVfTRW5ITVJ?
ALL-PO MonMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkL2TWM2OD1|LkG4NlA4KM7:TR?= NXLVT2RbW0GQR1XS
KS-1 NV74XINYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXnJR|UxRTNwMkGyNlUh|ryP NYXYXHdjW0GQR1XS
Becker MlfXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVnpPXNyUUN3ME20MlI{QTNizszN MX3TRW5ITVJ?
GDM-1 MnLHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYn0WmE4UUN3ME20MlI1PjF5IN88US=> M3zycXNCVkeHUh?=
BC-1 MoTtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGe3cnpKSzVyPUSuOFkzPzdizszN M1zqVHNCVkeHUh?=
NB14 NHLLU41Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn65TWM2OD12LkizOVI1KM7:TR?= NGnhdGNUSU6JRWK=
NOS-1 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmfuTWM2OD13LkOzPFc1KM7:TR?= Mn63V2FPT0WU
MZ1-PC MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2Ppb2lEPTB;NT64NlE2OSEQvF2= MVXTRW5ITVJ?
A498 M4DscGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3vhdWlEPTB;Nj6wPFQ4OyEQvF2= NIn0NW9USU6JRWK=
EW-16 NYX1VIRuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIW5SXNKSzVyPU[uN|c4PzNizszN M{\ySXNCVkeHUh?=
NALM-6 NWPtSnplT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4HtW2lEPTB;Nj62PFM5PyEQvF2= NVH4RlFqW0GQR1XS
EB-3 MlrrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mmq3TWM2OD15LkC3NlM{KM7:TR?= MlTPV2FPT0WU
697 MkTWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3;hTmlEPTB;OT6yOFMzQSEQvF2= NGrPVWFUSU6JRWK=
Ramos-2G6-4C10 M3fVPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIPpOmtKSzVyPUmuOVk5PDJizszN MYTTRW5ITVJ?
KNS-81-FD M2TjRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF;MT2FKSzVyPUmuOlk3PTNizszN NHfzUndUSU6JRWK=
HUTU-80 NGKzd3hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MojkTWM2OD17Lke0OlQzKM7:TR?= M2WxdnNCVkeHUh?=
LS-411N NI\vW4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXvvbWxPUUN3ME2xNE4xPTZ5IN88US=> NHPsellUSU6JRWK=
RPMI-8402 MmDiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVPtT5J{UUN3ME2xNE4yOTZizszN MX;TRW5ITVJ?
KU812 NWLuN4V2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWTVdJJHUUN3ME2xNE4zQTlzIN88US=> MXTTRW5ITVJ?
EW-1 NVjtdYF1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mnv6TWM2OD1zMD60OFI2KM7:TR?= MYDTRW5ITVJ?
HC-1 NEjMN29Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NE\4WVVKSzVyPUGwMlQ5PDRizszN MoPHV2FPT0WU
NB69 MlzUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWTWRVQyUUN3ME2xNE42ODR|IN88US=> Mly0V2FPT0WU
MFH-ino M2LB[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{LtVWlEPTB;MUCuPFMxOyEQvF2= NIm3XI1USU6JRWK=
CCRF-CEM MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGjYdWdKSzVyPUGxMlU6PyEQvF2= M{jTdnNCVkeHUh?=
SK-N-DZ NUPVfGg4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYjJR|UxRTF{LkC0N|Yh|ryP NYfPcXJFW0GQR1XS
NCI-H720 MoDVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXPIRndWUUN3ME2xNk4yPzB3IN88US=> NGjRU|FUSU6JRWK=
HCC1187 MmeyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV\1dGVMUUN3ME2xNk4zODRzIN88US=> NGC4XnVUSU6JRWK=
IST-SL2 MnrhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{nQUmlEPTB;MUKuOFg4OiEQvF2= NVLZd3lnW0GQR1XS
KE-37 NFyyPIZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVvpT2lvUUN3ME2xNk44QTZ4IN88US=> M2H1cXNCVkeHUh?=
HCC1599 NX\nTZBzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIPCenVKSzVyPUGyMlkxPjlizszN NUjldpR6W0GQR1XS
A4-Fuk MmXtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWPXOVlIUUN3ME2xNk46PTh4IN88US=> NI\iNo1USU6JRWK=
NKM-1 NHvCfFdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoTITWM2OD1zMz6yPVI2KM7:TR?= MnHxV2FPT0WU
BE-13 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlPPTWM2OD1zMz63PVg6KM7:TR?= NVryWHo3W0GQR1XS
MV-4-11 NXnRdGdNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWHJR|UxRTF2LkCzNlQh|ryP NYjRZ4xzW0GQR1XS
OPM-2 MkXDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NISxRWxKSzVyPUG0MlQxQDVizszN NVnnepBnW0GQR1XS
KARPAS-422 NXO4OHg2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MljuTWM2OD1zND61NVI3KM7:TR?= NYC2[WlGW0GQR1XS
RPMI-8226 MmqxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH\0dVFKSzVyPUG0Mlg6OTVizszN M1XOXXNCVkeHUh?=
KARPAS-45 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnOzTWM2OD1zNT63O|E3KM7:TR?= M4XX[XNCVkeHUh?=
SK-PN-DW M{XNPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkTRTWM2OD1zNT64OlMyKM7:TR?= NYLH[VBvW0GQR1XS
LC-2 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV;veHpkUUN3ME2xOk4yPTB4IN88US=> MULTRW5ITVJ?
NCI-H1648 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF;EfmVKSzVyPUG2MlI2PCEQvF2= NF23bFNUSU6JRWK=
RL95-2 NYHaeVdoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYPJR|UxRTF4LkO5O|gh|ryP MWjTRW5ITVJ?
KNS-42 NHe1em5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHPQZXZKSzVyPUG2MlczPzRizszN MYLTRW5ITVJ?
RPMI-6666 Mny2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3X4O2lEPTB;MU[uPVIyOSEQvF2= MYDTRW5ITVJ?
SIG-M5 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHuxVo1KSzVyPUG3MlE6ODNizszN NGHublhUSU6JRWK=
VA-ES-BJ MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHHwNmlKSzVyPUG3Mlc1PTFizszN NF;Kd3hUSU6JRWK=
MONO-MAC-6 Moj4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{L0Z2lEPTB;MUeuPVMyOiEQvF2= NFLWXVZUSU6JRWK=
LAN-6 NF7jc4NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnXLTWM2OD1zOD63OVU4KM7:TR?= NUPaflJXW0GQR1XS
A388 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYTtTIhJUUN3ME2xPU4{ODV7IN88US=> MlXPV2FPT0WU
SK-NEP-1 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHzxW4pKSzVyPUKwMlIyOzJizszN NVH6ZYFmW0GQR1XS
TE-10 NFfuRotIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3PaNmlEPTB;MkCuOVIzOSEQvF2= MWfTRW5ITVJ?
HL-60 NVjKNZhET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWmzOXhSUUN3ME2yNE46ODl7IN88US=> NH;RR|ZUSU6JRWK=
MC116 NHvGOHFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWrJR|UxRTJzLkeyNlEh|ryP MVfTRW5ITVJ?
SW962 Mni3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV6wdnN6UUN3ME2yNU44QTF3IN88US=> NXL2bFlDW0GQR1XS
NOMO-1 NX3QVYZFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4PDXmlEPTB;MkKuOlU3PCEQvF2= NXr0dXExW0GQR1XS
CTB-1 M{PtcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2rvemlEPTB;MkKuPFY4OSEQvF2= NYrlfXdEW0GQR1XS
MRK-nu-1 NXT6PJJlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWHnXpRNUUN3ME2yNk46ODd2IN88US=> NELBd2tUSU6JRWK=
GR-ST M1O5bGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2DGT2lEPTB;MkOuO|Yh|ryP NXGweGxlW0GQR1XS
HH MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWLJR|UxRTJ2LkCwN{DPxE1? M4DhRnNCVkeHUh?=
NCI-H1963 MkjuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlrhTWM2OD1{ND6wO|gzKM7:TR?= MlXrV2FPT0WU
QIMR-WIL MlPVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M121W2lEPTB;MkSuPFc4OiEQvF2= MkDDV2FPT0WU
CGTH-W-1 NHvQZZRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVLIUWRlUUN3ME2yOU4xPzJ|IN88US=> NEPYXY5USU6JRWK=
LP-1 Mo\zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4LafGlEPTB;MkWuOlU2OSEQvF2= MWjTRW5ITVJ?
NCI-H748 M4nYR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFP6VmhKSzVyPUK2MlUyOzdizszN NHLXR4ZUSU6JRWK=
PF-382 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYTHPJFoUUN3ME2yO{4zOjJ|IN88US=> MkGxV2FPT0WU
ATN-1 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHHUcolKSzVyPUK3MlM4OzJizszN MnjvV2FPT0WU
L-540 NEfkeVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVjyS4tPUUN3ME2yO{43PDV7IN88US=> MlPRV2FPT0WU
LXF-289 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXTJR|UxRTJ5Lke1NVkh|ryP NYH6PZM4W0GQR1XS
LS-513 M3HSTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWG3OlJMUUN3ME2yPE4yQDB5IN88US=> MXrTRW5ITVJ?
NCI-H1581 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGjESIRKSzVyPUOwMlM6PzZizszN NE\yOHVUSU6JRWK=
ES6 Mmi1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlHaTWM2OD1|MD62PFk6KM7:TR?= MVPTRW5ITVJ?
SW982 MmTKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFHtb4hKSzVyPUOwMlg2PjZizszN M1fndHNCVkeHUh?=
DOHH-2 MknkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{DtTmlEPTB;M{GuOVg6OyEQvF2= NVmxV4NGW0GQR1XS
DB MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFLzO|lKSzVyPUOzMlk1OzFizszN MmHlV2FPT0WU
MPP-89 NXXxcopuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3zQRWlEPTB;M{SuNVc2PiEQvF2= Mo\WV2FPT0WU
LB831-BLC MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlzsTWM2OD1|ND61NVg1KM7:TR?= NYX0RZFYW0GQR1XS
NB5 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnvnTWM2OD1|ND64OVM2KM7:TR?= NYnmbHBbW0GQR1XS
GB-1 NXTaOotrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHjKXmlKSzVyPUO1MlA1PjlizszN Ml:xV2FPT0WU
TE-15 NXGzfZV6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3S5eWlEPTB;M{WuNlI{QCEQvF2= M4LjNnNCVkeHUh?=
LC4-1 NVv4c2lGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkLrTWM2OD1|NT6zPFQ4KM7:TR?= M1[xbHNCVkeHUh?=
NCI-H747 MnnZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYjJR|UxRTN4LkGzOlkh|ryP NHjWfndUSU6JRWK=
NTERA-S-cl-D1 NYjFZVRrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUnJR|UxRTN6LkezOFch|ryP NVjDc4VzW0GQR1XS
SK-MM-2 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHj6RnBKSzVyPUSwMlEyPDZizszN NVezcFRHW0GQR1XS
TGW NILaN2xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkLVTWM2OD12MT6wOVY{KM7:TR?= MmnhV2FPT0WU
ONS-76 M4S2OWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYX5R4V1UUN3ME20Nk41QDh|IN88US=> M1fOU3NCVkeHUh?=
CPC-N M3rENWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXvJR|UxRTR{Lkm5O|Eh|ryP NYXN[G1OW0GQR1XS
ES4 Ml;GS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{fpTWlEPTB;NESuOFE2OyEQvF2= MX7TRW5ITVJ?
Daudi M2fGPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2nMTWlEPTB;NEWuNFgzPyEQvF2= M{KwRXNCVkeHUh?=
MOLT-4 NFjINGJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYHJR|UxRTR3LkC4OVMh|ryP MkSxV2FPT0WU
HT-144 NF:1UmlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIPpXY9KSzVyPUS2MlczPiEQvF2= MXnTRW5ITVJ?
SW872 NXzFfWxDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUSwcYNWUUN3ME20PE4yQTN|IN88US=> M3T3c3NCVkeHUh?=
D-283MED NIDXRWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Moe1TWM2OD12OD6zOVQzKM7:TR?= NGDSVmxUSU6JRWK=
NCI-H2126 NY\kN3EzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWHIZ4k2UUN3ME20PE45PDd4IN88US=> NUXEc4M4W0GQR1XS
NCI-SNU-16 NUe5bmIxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlXOTWM2OD12OT6yNVQ{KM7:TR?= NGjrUpBUSU6JRWK=
CESS MonTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3TXc2lEPTB;NEmuOVA5QCEQvF2= MkOxV2FPT0WU
A101D NITY[HFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MULJR|UxRTR7Lkm3N|Yh|ryP MkK3V2FPT0WU

... 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(C1=C(C=CC(=C1Cl)F)Cl)OC2=C(N=CC(=C2)C3=CN(N=C3)C4CCNCC4)N

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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