Crizotinib (PF-02341066) 化学構造
分子量: 450.34

高品質保証

文献中の引用(65)

カスタマーフィードバック(8)

Quality Control & MSDS

製品説明

  • Compare c-Met Inhibitors
    c-Met製品生物活性の比較
  • 研究分野
  • Combination Therapy
    併用療法
  • Crizotinib (PF-02341066)のメカニズム

製品の説明

生物活性

製品説明 Crizotinib (PF-02341066) は1種の有効な小分子の卵白の阻害剤の再編人プロテインキナーゼ、 Kiが 4 nM。
ターゲット c-Met ALK
IC50 11 nM 24 nM [1]
In vitro試験 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
BAF3 NITUUGREgXSxdH;4bYMhSXO|YYm= MX:0PEBp MVjEUXNQ NFnGOYhEgXSxdH;4bYNqfHliYXfhbY5{fCCvb4Xz[UBDSUZ|IHPlcIx{KGW6cILld5NqdmdiQVzLJGYyOTd2TDDteZRidnRiY3;lfJBz\XO|aX7nJGVOVDRid3n0bEBKSzVyIH;mJFAvPjJizszN MmKzNlE2PzJ3OEm=
BAF3 NIP6cGZEgXSxdH;4bYMhSXO|YYm= MoLKOFghcA>? M1f5UGROW09? NFXDNnVEgXSxdH;4bYNqfHliYXfhbY5{fCCvb4Xz[UBDSUZ|IHPlcIx{KGW6cILld5NqdmdiQVzLJGwyOTl4TTDteZRidnRiY3;lfJBz\XO|aX7nJGVOVDRid3n0bEBKSzVyIH;mJFIvOiEQvF2= NUfXOZpPOjF3N{K1PFk>
BAF3 NYrYNJZ7S3m2b4TvfIlkKEG|c3H5 M{jiflQ5KGh? NILyenZFVVOR NXq4Wmc1S3m2b4TvfIlkcXS7IHHnZYlve3RibX;1d4UhSkGIMzDj[YxteyCneIDy[ZN{cW6pIFXNUFQuSUyNIIfpeIghUUN3MDDv[kAxNjJ6IN88US=> NIToSm8zOTV5MkW4PS=>
Kelly MonpR5l1d3SxeHnjJGF{e2G7 MoDTSG1UVw>? NFTNe5VEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBM\WyueTDj[YxteyCneIDy[ZN{cW6pIFHMT{BHOTF5NFygcZV1[W62IIfpeIghUUN3MDDv[kAxNjR{IN88US=> NWrSbmc6OjF3N{K1PFk>
SH-SY5Y NH;QTIFEgXSxdH;4bYMhSXO|YYm= M33kSmROW09? M36zOmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHNJNVO\NWmgZ4VtdHNiZYjwdoV{e2mwZzDBUGshTjFzN{TMJI12fGGwdDD3bZRpKEmFNUCgc4YhOC53MzFOwG0> NUfZNZRlOjF3N{K1PFk>
SMS-KCN MkDLR5l1d3SxeHnjJGF{e2G7 MlLPSG1UVw>? MlnaR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV21UNUuFTjDj[YxteyCneIDy[ZN{cW6pIFHMT{BTOTJ5NWGgcZV1[W62IIfpeIghUUN3MDDv[kAxNjlzIN88US=> NH[xdXozOTV5MkW4PS=>
BAF3 M{TVW2N6fG:2b4jpZ{BCe3OjeR?= NXjicVBmPDhiaB?= MoGySG1UVw>? NWrWeW5LS3m2b4TvfIlkcXS7IHHnZYlve3RibX;1d4UhSkGIMzDj[YxteyCneIDy[ZN{cW6pIGTlcE1CVEtid3n0bEBKSzVyIH;mJFAvOTlizszN NIXjTmgzOTV5MkW4PS=>
3T3 MUHGeY5kfGmxbjDBd5NigQ>? NXq4OFhpOSCq NUHXXXRxTE2VTx?= NFzaVFdKdmirYnn0bY9vKG:oIGLPUkBie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6wPEDPxE1? NFPFfnMzOThzMkSxOC=>
3T3-E NYqwS5hmTnWwY4Tpc44hSXO|YYm= M2j4R|EhcA>? MoTqSG1UVw>? M2rnTGlvcGmkaYTpc44hd2ZiVFnFNkBie3Onc4Pl[EBoem:5dHig[oFkfG:{LXnu[JVk\WRiYYX0c5Bpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOC52NEig{txO M1T5S|IyQDF{NEG0
A549 NGn3c4FMcW6jc3WgRZN{[Xl? MkPYNUBp MV7EUXNQ Mn;WTY5pcWKrdHnvckBw\iCqdX3hckBz\WOxbXLpcoFvfCClLV3FWEBscW6jc3Wg[ZhxemW|c3XkJIF{e2W|c3XkJIF{KGmwaHnibZRqd25ib3[gTGdHNWmwZIXj[YQh[XW2b4Doc5NxcG:{eXzheIlwdiC5aYToJGlEPTBib3[gNE4xODhizszN MUmyNVgyOjRzNB?=
BAF3-BCL MonvSpVv[3Srb36gRZN{[Xl? MX6xJIg> NEHWbXFFVVOR NWH6[IlIUW6qaXLpeIlwdiCxZjDBRmwh[XO|ZYPz[YQh[XNiZ4Lve5RpKG[jY4Tvdk1qdmS3Y3XkJIF2fG:yaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIEGuNVU6KM7:TR?= M2TPWFIyQDF{NEG0
HEK293 NWTnR2J2TnWwY4Tpc44hSXO|YYm= NYTBd4xiOSCq MoTGSG1UVw>? MYXJcohq[mm2aX;uJI9nKEG[TDDhd5Nme3OnZDDhd{Boem:5dHig[oFkfG:{LXnu[JVk\WRiYYX0c5Bpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOC5{OUSg{txO Mn:3NlE5OTJ2MUS=
HEK293 MWrGeY5kfGmxbjDBd5NigQ>? NILZVnYyKGh? MonISG1UVw>? NW\hd|ZTUW6qaXLpeIlwdiCxZjDJVkBie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMj64PFch|ryP NV;qVms1OjF6MUK0NVQ>
Jurkat MYPGeY5kfGmxbjDBd5NigQ>? NF3GTJEyKGh? Mn;oSG1UVw>? NHrqRVdKdmirYnn0bY9vKG:oIFzDT{Bie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMj63OFEh|ryP NWXRc5FJOjF6MUK0NVQ>
KARPAS299 NHu0[YpMcW6jc3WgRZN{[Xl? NEXjeo8yKGh? M1:3OWROW09? M4ixTGlvcGmkaYTpc44hd2ZiQVzLJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iByLkCyJO69VQ>? M3[w[VIyQDF{NEG0
PAE NF7vZVJHfW6ldHnvckBCe3OjeR?= NHXybFQyKGh? Mlu4SG1UVw>? MmnOTY5pcWKrdHnvckBw\iCWUlvCJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iByLkO5PUDPxE1? NH3nSG0zOThzMkSxOC=>
BAF3 MWTGeY5kfGmxbjDBd5NigQ>? NUO0bHFJOi1|IHS= NHfoZlNFVVOR M1jVPWlvcGmkaYTpc44hd2ZiVFXMMYZ2e2WmIHnud5VtcW5icnXj[ZB1d3JiZYjwdoV{e2WmIIfpeIghUUN3MDDv[kAyNjZ2MzFOwG0> MofHNlM4PDJ{NUK=
KARPAS299 NEDDV2xEgXSxdH;4bYMhSXO|YYm= NGT1PIwzNTNiZB?= NIDkV3dFVVOR NXnKSmlDUUN3ME2wMlA3PDJizszN M{DBblI{PzR{MkWy
EBC1 NV3xS5JCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXm3NkBp NH3NXXdFVVOR MY\JR|UxRTBwMEKzJO69VQ>? M2rEdFI{QTl|M{K4
HCT116 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIfWTIg4OiCq MlTxSG1UVw>? MULJR|UxRTF2LkiyJO69VQ>? NIfjTYIzOzl7M{OyPC=>
MCF7 NUDCWppGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHvPTVI4OiCq MXrEUXNQ NH:3UWZKSzVyPUmuOVgh|ryP MlL6NlM6QTN|Mki=
MDA-MB-231 NEfPUYdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1PCU|czKGh? MVfEUXNQ NFSxbZJKSzVyPUGwMlgh|ryP MoHjNlM6QTN|Mki=
MKN45 NILnWIJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVPLcppRPzJiaB?= NVSzXXE3TE2VTx?= NYjQb21kUUN3ME2wMlAyOyEQvF2= MXqyN|k6OzN{OB?=
NCI-H441 NVXPUWs4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEPLd3M4OiCq NYfhOG92TE2VTx?= NH62RYJKSzVyPUG3MlI2KM7:TR?= M2Xy[|I{QTl|M{K4
NCI-H661 NH:0TlhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH7tfGY4OiCq NXq0dG9oTE2VTx?= NUPuZlVOUUN3ME2xNU41PyEQvF2= NVHGdXBkOjN7OUOzNlg>
SK-MEL-28 MkPaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NW\0W2hJPzJiaB?= MVfEUXNQ MoPaTWM2OD1zMD65O{DPxE1? NWD5Z41XOjN7OUOzNlg>
SKOV3 M1;yWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUX2UYR4PzJiaB?= NWD6SFNnTE2VTx?= MlfBTWM2OD1zMj64OUDPxE1? MYiyN|k6OzN{OB?=
SNU5 NFrpb45Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MonIO|IhcA>? M3TnNGROW09? MnvjTWM2OD1yLkCxOkDPxE1? Mn3jNlM6QTN|Mki=
NCI-H2228 NHfoT5NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGK1Xmo4OiCq NHnxWWtFVVOR NITv[YZKdmirYnn0bY9vKG:oIFHMT{1nfXOrb36g[JJqfmWwIHPlcIwheHKxbHnm[ZJifGmxbjD3bZRpKEmFNUCgc4YhOC5zMUig{txO NH[2Z3IzPDR|MkmwPS=>
NCI-H3122 NHPXbXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmjMO|IhcA>? NF30U2lFVVOR Mnz2TY5pcWKrdHnvckBw\iCDTFut[pV{cW:wIHTybZZmdiClZXzsJJBzd2yrZnXyZZRqd25id3n0bEBKSzVyIH;mJFAvOTB6IN88US=> M2j4bFI1PDN{OUC5
NCI-H3122 MlnUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX[3NkBp MnjpSG1UVw>? Mm\ETY5pcWKrdHnvckBw\iCDTFut[pV{cW:wIHTybZZmdiClZXzsJJBzd2yrZnXyZZRqd25iaX6gbJVu[W5iTlPJMWg{OTJ{IHPlcIx{KGijcnLvdolv\yCDTFugS|EzPjmDIH31eIFvfCC5aYToJGlEPTBib3[gNE43OjNizszN MYGyOFQ{OjlyOR?=
NCI-H3122 MkG3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4TqdlczKGh? NXTsNY9yTE2VTx?= MnrNTY5pcWKrdHnvckBw\iCDTFut[pV{cW:wIHTybZZmdiClZXzsJJBzd2yrZnXyZZRqd25iaX6gbJVu[W5iTlPJMWg{OTJ{IHPlcIx{KGijcnLvdolv\yCDTFugUFEyQT[PIH31eIFvfCC5aYToJGlEPTBib3[gNE45OzhizszN M1;UWFI1PDN{OUC5
NIH-3T3 MWrLbY5ie2ViQYPzZZk> NUfWOIIxOSCq NGXNdm5FVVOR MWrJcohq[mm2aX;uJI9nKGi3bXHuJJdqdGRidInw[UBGVUx2LX\1d4VlKEGOSzDlfJBz\XO|ZXSgZZN{\XO|ZXSgZZMheGixc4Doc5J6dGG2ZXSgRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLkC4JO69VQ>? NHLQcYEzPDR|MkmwPS=>
NIH-3T3 NFfB[GVMcW6jc3WgRZN{[Xl? M2LCXVEhcA>? M3HoV2ROW09? NWjjN3gxUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BIOTJ4OVGgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMD62NFUh|ryP MV:yOFQ{OjlyOR?=
NIH-3T3 NE\j[ZVMcW6jc3WgRZN{[Xl? MV6xJIg> NHHsfm9FVVOR NWe2Z49wUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BUOTJyNmmgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMD62NlYh|ryP MWSyOFQ{OjlyOR?=
NIH-3T3 MYLLbY5ie2ViQYPzZZk> MnTFNUBp M2Dkb2ROW09? M2G0WmlvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugUFEyQT[PIH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDBwOESzJO69VQ>? NIDtUlQzPDR|MkmwPS=>
NIH-3T3 MkTaT4lv[XOnIFHzd4F6 MWmxJIg> M3LuSmROW09? MX7Jcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIFyxNVUzWiCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAyNjB{NjFOwG0> NIPjcmozPDR|MkmwPS=>
BAF3 MVTGeY5kfGmxbjDBd5NigQ>? MUG3NkBp MYPEUXNQ MWXJcohq[mm2aX;uJI9nKE6STT;BUGshfHKjboPm[YN1\WRiYYPz[ZN{\WRiYYOgZ4VtdCCpcn;3eIghcW6qaXLpeIlwdiC5aYToJGlEPTBib3[gNE4xPTFizszN NHXscIwzPDR4OE[zNi=>
BAF3 M2P3dWN6fG:2b4jpZ{BCe3OjeR?= MnzTO|IhcA>? NXez[IxQTE2VTx?= MWDJR|UxRTBwOUig{txO NUDXb2hZOjR2Nki2N|I>
NIH-3T3 MUfLbY5ie2ViQYPzZZk> MkD2NUBp MWnJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIF[xNVc1VCCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAxNjF4NTFOwG0> NUXXPHVvOjR6MUmxNVY>
NIH-3T3 MYDLbY5ie2ViQYPzZZk> M{DBXFEhcA>? NYTtW2RxUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BEOTF3NmmgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMD60O|gh|ryP MmrhNlQ5OTlzMU[=
NIH-3T3 NWrPNlJHU2mwYYPlJGF{e2G7 MlSxNUBp MVLJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIFexNlAzWiCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAyNjF2ODFOwG0> Ml\6NlQ5OTlzMU[=
NIH-3T3 MlLwT4lv[XOnIFHzd4F6 NYHwXlhEOSCq MkTTTY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzCxNVUyXGmwczDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iB|LkCzPUDPxE1? MXOyOFgyQTFzNh?=
KARPAS299 M1zlbWtqdmG|ZTDBd5NigQ>? NVHWe4JtQTBibXnu MXrEUXNQ NX3RcmE5UW6qaXLpeIlwdiCxZjDOVG0u\nW|ZXSgRWxMKHCqb4PwbI9zgWyjdHnvckBmgHC{ZYPz[YQhf2m2aDDJR|UxKG:oIECuNVEh|ryP MWiyOFkxODd3MB?=
MKN 45 M1\h[mtqdmG|ZTDBd5NigQ>? NV\kVYZTOSCq NV3iNoE1TE2VTx?= NVPORod{UW6qaXLpeIlwdiCxZjDjMW1mfCCyaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIECuNFIh|ryP MUeyOFkxODd3MB?=
A549 MWTDfZRwfG:6aXOgRZN{[Xl? MVe0PEBp MnXoSG1UVw>? NXG2bFl6UUN3MDDv[kA1NjB6NDFOwG0> MnjwNlQ6ODB6M{C=
NCI-H1975 M{\rW2N6fG:2b4jpZ{BCe3OjeR?= NXTlOWVEPDhiaB?= MXTEUXNQ NF[1WFBKSzVyIH;mJFcvPTVzIN88US=> NHfKbYczPDlyMEizNC=>
NCI-H1993 MV\DfZRwfG:6aXOgRZN{[Xl? NYSyfo9XPDhiaB?= NXnIfGdQTE2VTx?= MXHJR|UxKG:oIECuNFYyKM7:TR?= MmnFNlQ6ODB6M{C=
NCI-H1993 NVe1WGs4SXCxdH;zbZMhSXO|YYm= M1;2SFEh|ryP M2n4S|I1KGh? Mk\6SG1UVw>? M1S1WIRw\XNibn;0JIlv\HWlZTDhdI9xfG:|aYO= MXeyOFkxODh|MB?=
NIH-3T3 NInudIpEgXSxdH;4bYMhSXO|YYm= NYPt[VhoPDhiaB?= MmnqSG1UVw>? MVvJR|UxKG:oIECuN|Y1KM7:TR?= NY\LOHAxOjR7MEC4N|A>
EBC1 NIT4S4RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWi3NkBp M4TN[WROW09? NYjhNldXUUN3MDDv[kAxNjByNkmg{txO MUCyOFkxODh|MR?=
KARPAS299 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGH3e4o4OiCq NVqxcY9xTE2VTx?= MWjJR|UxKG:oIECuNkDPxE1? MWWyOFkxODh|MR?=
NB1 NUL3bGk5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVjlXmhsUUN3ME25NU46QCCwTR?= MXPTRW5ITVJ?
NCI-SNU-5 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHfjT2lKSzVyPUGwOU44PSCwTR?= MULTRW5ITVJ?
SR M2Ht[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NELvR3JKSzVyPUGyOk4{OSCwTR?= NH:4ZW9USU6JRWK=
SF539 NF;4WGpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2jwO2lEPTB;MkC0MlI1KG6P M4DZNHNCVkeHUh?=
SU-DHL-1 M1T0WGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4rsOWlEPTB;M{O2MlgzKG6P NGrjTnpUSU6JRWK=
SCC-3 NYHyVo5FT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVrJR|UxRTN3Nj63OkBvVQ>? MUXTRW5ITVJ?
DEL Ml\JS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1n2SmlEPTB;M{[5Mlkhdk1? M{LLdnNCVkeHUh?=
CTV-1 M4P5Rmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEDBZ2xKSzVyPUW5Ok41QCCwTR?= MXfTRW5ITVJ?
EM-2 NV;Xb2l2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVfJR|UxRTZyMT6zOEBvVQ>? NHLKVmRUSU6JRWK=
MHH-CALL-2 NIDyPG9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEnSWVBKSzVyPU[4Nk42PyCwTR?= M1P1fnNCVkeHUh?=
KM12 NWjVUXhkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4f3e2lEPTB;N{C2Mlkhdk1? MkXZV2FPT0WU
KINGS-1 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MorBTWM2OD15NEmuO|Uhdk1? MmHHV2FPT0WU
MEG-01 M3rjcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mo\xTWM2OD16NUeuOlYhdk1? MXvTRW5ITVJ?
BV-173 NYXTeW9DT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWfWU2RxUUN3ME2xMlA2QTl5IN88US=> MX\TRW5ITVJ?
LAMA-84 MnXSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mlm0TWM2OD1zLkO4NlgzKM7:TR?= Mmq0V2FPT0WU
KARPAS-299 NGnCeXpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{\SSGlEPTB;MT60NFg3OSEQvF2= MYfTRW5ITVJ?
K-562 NUiyeJJQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFvyOphKSzVyPUGuO|IzPjlizszN NIDwTlBUSU6JRWK=
SK-LMS-1 M2fvZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M361VmlEPTB;MT63Olg3PyEQvF2= MnS3V2FPT0WU
MOLT-16 NFKzZZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVjJR|UxRTFwOUW1O|Uh|ryP M{PHVXNCVkeHUh?=
CMK NX3ZTpNTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mm[yTWM2OD1zLkm2NVU6KM7:TR?= NHLLN|ZUSU6JRWK=
ST486 NXvWU2RGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlLoTWM2OD1{LkSzNFc{KM7:TR?= NGTaXoNUSU6JRWK=
CI-1 NWHPW4Q{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFrwNnVKSzVyPUKuOFk3PTlizszN Mor3V2FPT0WU
KP-N-RT-BM-1 MoHtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVTWSGl3UUN3ME2yMlcxOTJ{IN88US=> NFHWdo9USU6JRWK=
ALL-PO MnG1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlTtTWM2OD1|LkG4NlA4KM7:TR?= NWjRR3pHW0GQR1XS
KS-1 MmrRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWTUe49QUUN3ME2zMlIyOjJ3IN88US=> NV2xenFKW0GQR1XS
Becker NWiydFVMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHfyNlRKSzVyPUSuNlM6OyEQvF2= NG\y[WZUSU6JRWK=
GDM-1 MofiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlzkTWM2OD12LkK0OlE4KM7:TR?= NY\ZblNIW0GQR1XS
BC-1 M2Lsc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXr0dXgzUUN3ME20MlQ6Ojd5IN88US=> MWjTRW5ITVJ?
NB14 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYfJR|UxRTRwOEO1NlQh|ryP MojMV2FPT0WU
NOS-1 NIrIOHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWXOTnlzUUN3ME21MlM{QDd2IN88US=> MnfWV2FPT0WU
MZ1-PC M1PxVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVS5NZRTUUN3ME21MlgzOTVzIN88US=> M4LLN3NCVkeHUh?=
A498 NFGxR3BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml\lTWM2OD14LkC4OFc{KM7:TR?= MUnTRW5ITVJ?
EW-16 NGrORY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnLVTWM2OD14LkO3O|c{KM7:TR?= MYXTRW5ITVJ?
NALM-6 NWfrTYhJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXjJR|UxRTZwNkizPFch|ryP NH:wU4dUSU6JRWK=
EB-3 MofZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MofTTWM2OD15LkC3NlM{KM7:TR?= MYDTRW5ITVJ?
697 NFjZWY1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUHJR|UxRTlwMkSzNlkh|ryP MlHKV2FPT0WU
Ramos-2G6-4C10 M1fPXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWTJR|UxRTlwNUm4OFIh|ryP NUO5cpFzW0GQR1XS
KNS-81-FD Mk[4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGTu[mtKSzVyPUmuOlk3PTNizszN MXnTRW5ITVJ?
HUTU-80 NVKzXnpVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1rRTWlEPTB;OT63OFY1OiEQvF2= NXfaWVdPW0GQR1XS
LS-411N MmnCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXTJR|UxRTFyLkC1Olch|ryP M2KxVXNCVkeHUh?=
RPMI-8402 M1y4PGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mo\MTWM2OD1zMD6xNVYh|ryP NVrEN2h5W0GQR1XS
KU812 NIrWOHBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1KyWmlEPTB;MUCuNlk6OSEQvF2= NVG0WlQ2W0GQR1XS
EW-1 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH3reXFKSzVyPUGwMlQ1OjVizszN MV;TRW5ITVJ?
HC-1 M1rjbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlnzTWM2OD1zMD60PFQ1KM7:TR?= NIj1e2xUSU6JRWK=
NB69 NV22R5VKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX7JR|UxRTFyLkWwOFMh|ryP MUnTRW5ITVJ?
MFH-ino NXPjToJ1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGTIWm5KSzVyPUGwMlg{ODNizszN MmDyV2FPT0WU
CCRF-CEM M4PhcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlLnTWM2OD1zMT61PVch|ryP NFz4bXRUSU6JRWK=
SK-N-DZ NGfIV5pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{f2NmlEPTB;MUKuNFQ{PiEQvF2= M4\MdXNCVkeHUh?=
NCI-H720 MkXQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYDJR|UxRTF{LkG3NFUh|ryP NUnNZ|dYW0GQR1XS
HCC1187 M3W4[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml7rTWM2OD1zMj6yNFQyKM7:TR?= NXe4VI9VW0GQR1XS
IST-SL2 M3S1bmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4XHPGlEPTB;MUKuOFg4OiEQvF2= M{nVfXNCVkeHUh?=
KE-37 M{jBVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHf5ToFKSzVyPUGyMlc6PjZizszN NEHwbFdUSU6JRWK=
HCC1599 Ml3wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmjYTWM2OD1zMj65NFY6KM7:TR?= NWjTS2hmW0GQR1XS
A4-Fuk NYWwcHgxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYW2[4U5UUN3ME2xNk46PTh4IN88US=> MmrsV2FPT0WU
NKM-1 M37KNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEC0bXpKSzVyPUGzMlI6OjVizszN MXnTRW5ITVJ?
BE-13 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1XKbmlEPTB;MUOuO|k5QSEQvF2= MkjKV2FPT0WU
MV-4-11 M2jCbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXfSWHpHUUN3ME2xOE4xOzJ2IN88US=> NIe0NWpUSU6JRWK=
OPM-2 NWW4fmNxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoD6TWM2OD1zND60NFg2KM7:TR?= NYXMN295W0GQR1XS
KARPAS-422 NELOeZBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoTJTWM2OD1zND61NVI3KM7:TR?= MmTPV2FPT0WU
RPMI-8226 NHK2fo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3\4emlEPTB;MUSuPFkyPSEQvF2= NFOxcIFUSU6JRWK=
KARPAS-45 M13JNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH3heFRKSzVyPUG1Mlc4OTZizszN M37GcXNCVkeHUh?=
SK-PN-DW NVXUWYZkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1fVVGlEPTB;MUWuPFY{OSEQvF2= M3jpTnNCVkeHUh?=
LC-2 NIPaUGZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXTaT2h3UUN3ME2xOk4yPTB4IN88US=> NXLGSHRoW0GQR1XS
NCI-H1648 NYHvXnJ7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIHxdIFKSzVyPUG2MlI2PCEQvF2= MnzxV2FPT0WU
RL95-2 NX;GU4N3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIfIb3BKSzVyPUG2MlM6PzhizszN MVnTRW5ITVJ?
KNS-42 Ml7hS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFLjTYpKSzVyPUG2MlczPzRizszN Mn\aV2FPT0WU
RPMI-6666 NWDN[VQ5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHXm[ZBKSzVyPUG2MlkzOTFizszN M2L2THNCVkeHUh?=
SIG-M5 NYXXU2xET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1XQN2lEPTB;MUeuNVkxOyEQvF2= NWixVnpWW0GQR1XS
VA-ES-BJ M{PNb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MojOTWM2OD1zNz63OFUyKM7:TR?= M2TDdnNCVkeHUh?=
MONO-MAC-6 MonVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYHJR|UxRTF5LkmzNVIh|ryP NV;Nc3VIW0GQR1XS
LAN-6 NFK2fXJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1S2N2lEPTB;MUiuO|U2PyEQvF2= NFrEemdUSU6JRWK=
A388 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVrROZJGUUN3ME2xPU4{ODV7IN88US=> MXLTRW5ITVJ?
SK-NEP-1 Mn\mS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmHjTWM2OD1{MD6yNVMzKM7:TR?= NFzjcVdUSU6JRWK=
TE-10 M1jITWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1rXOGlEPTB;MkCuOVIzOSEQvF2= MlfOV2FPT0WU
HL-60 NV23WW04T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn22TWM2OD1{MD65NFk6KM7:TR?= M2HBVXNCVkeHUh?=
MC116 M2Pkcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV7JR|UxRTJzLkeyNlEh|ryP M4XTd3NCVkeHUh?=
SW962 NX;6W3BHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWLXdodEUUN3ME2yNU44QTF3IN88US=> NV7vS3BMW0GQR1XS
NOMO-1 NWO3O3BuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1LWOmlEPTB;MkKuOlU3PCEQvF2= MlP1V2FPT0WU
CTB-1 NV[zR2xOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3TFeGlEPTB;MkKuPFY4OSEQvF2= MV;TRW5ITVJ?
MRK-nu-1 Mnr6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYHJR|UxRTJ{LkmwO|Qh|ryP NH3VN2dUSU6JRWK=
GR-ST NYTUZW9UT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1fqb2lEPTB;MkOuO|Yh|ryP NYfkS4pTW0GQR1XS
HH Ml3mS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVi1NY17UUN3ME2yOE4xODNizszN MnPrV2FPT0WU
NCI-H1963 NETNVYNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXq1b4lsUUN3ME2yOE4xPzh{IN88US=> NV[xNIxYW0GQR1XS
QIMR-WIL MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2D0fWlEPTB;MkSuPFc4OiEQvF2= MnuzV2FPT0WU
CGTH-W-1 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYjJR|UxRTJ3LkC3NlMh|ryP NXXRPJhJW0GQR1XS
LP-1 MnnNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGPCTWJKSzVyPUK1MlY2PTFizszN M3\0dnNCVkeHUh?=
NCI-H748 M3T2bGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmXOTWM2OD1{Nj61NVM4KM7:TR?= M4nscnNCVkeHUh?=
PF-382 MkD5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NY\NZmZwUUN3ME2yO{4zOjJ|IN88US=> NUn2fFFXW0GQR1XS
ATN-1 NHPue5dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2flT2lEPTB;MkeuN|c{OiEQvF2= NXHuUWFbW0GQR1XS
L-540 NYC3eoR7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVjJR|UxRTJ5Lk[0OVkh|ryP M3PpdnNCVkeHUh?=
LXF-289 NXHWWZhYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3nSbGlEPTB;MkeuO|UyQSEQvF2= NULDcIM6W0GQR1XS
LS-513 M3PxWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2D3TGlEPTB;MkiuNVgxPyEQvF2= MmPMV2FPT0WU
NCI-H1581 NFvP[opIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn;xTWM2OD1|MD6zPVc3KM7:TR?= Mnf6V2FPT0WU
ES6 NXf3eplsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXzNVVRkUUN3ME2zNE43QDl7IN88US=> MmPkV2FPT0WU
SW982 M{XFSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3fqZWlEPTB;M{CuPFU3PiEQvF2= NF;PfFBUSU6JRWK=
DOHH-2 NIPHO4JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlnITWM2OD1|MT61PFk{KM7:TR?= MYPTRW5ITVJ?
DB MoPvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoL6TWM2OD1|Mz65OFMyKM7:TR?= MV\TRW5ITVJ?
MPP-89 NWPsemtTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlTFTWM2OD1|ND6xO|U3KM7:TR?= NIPtV2hUSU6JRWK=
LB831-BLC Mn\jS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYDJR|UxRTN2LkWxPFQh|ryP MX3TRW5ITVJ?
NB5 MmO2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVO0WWFEUUN3ME2zOE45PTN3IN88US=> MlzwV2FPT0WU
GB-1 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIjGN4NKSzVyPUO1MlA1PjlizszN MnT6V2FPT0WU
TE-15 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHqxNZNKSzVyPUO1MlIzOzhizszN M{DpSnNCVkeHUh?=
LC4-1 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1;XOmlEPTB;M{WuN|g1PyEQvF2= NHnueG5USU6JRWK=
NCI-H747 M2H3VWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHT2[ZBKSzVyPUO2MlE{PjlizszN NVvHXm95W0GQR1XS
NTERA-S-cl-D1 M4Wx[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWn4dYxqUUN3ME2zPE44OzR5IN88US=> NGDpXnRUSU6JRWK=
SK-MM-2 M2f0Nmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVPxNZp4UUN3ME20NE4yOTR4IN88US=> NXTpbJB1W0GQR1XS
TGW NID6flZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEXGUZdKSzVyPUSxMlA2PjNizszN MkLxV2FPT0WU
ONS-76 MkPrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFi0c|lKSzVyPUSyMlQ5QDNizszN MWfTRW5ITVJ?
CPC-N NIroN2ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkDsTWM2OD12Mj65PVcyKM7:TR?= NYLSdmZJW0GQR1XS
ES4 MnjYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYfMSY1[UUN3ME20OE41OTV|IN88US=> Moj5V2FPT0WU
Daudi NX3V[pVyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGj2cYdKSzVyPUS1MlA5OjdizszN M4\3cHNCVkeHUh?=
MOLT-4 MknmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWL2dGpUUUN3ME20OU4xQDV|IN88US=> NGrmR3dUSU6JRWK=
HT-144 M4i3XWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUXJR|UxRTR4LkeyOkDPxE1? NWOxT2FnW0GQR1XS
SW872 M1PtXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYLjNIppUUN3ME20PE4yQTN|IN88US=> NEHVWWNUSU6JRWK=
D-283MED NX[ycGdNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHLlWpBKSzVyPUS4MlM2PDJizszN MVzTRW5ITVJ?
NCI-H2126 M1voXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHyzfnRKSzVyPUS4Mlg1PzZizszN NHnTR4tUSU6JRWK=
NCI-SNU-16 MoLnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2eweGlEPTB;NEmuNlE1OyEQvF2= M1\nRnNCVkeHUh?=
CESS MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4W5c2lEPTB;NEmuOVA5QCEQvF2= MUHTRW5ITVJ?
A101D MnXBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH\2SVBKSzVyPUS5Mlk4OzZizszN NInEO4ZUSU6JRWK=

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In vivo試験 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]
臨床試験 PF-2341066 is currently in a Phase III clinical trial in the treatment of non squamous lung cancer.
特集

プロトコル (参考用のみ)

キナーゼアッセイ: [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.

細胞アッセイ: [1]

細胞株 GTL-16 gastric carcinoma cells and T47D breast carcinoma cells
濃度 0-256 nM
反応時間 1 hour
実験の流れ 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.

動物実験: [1]

動物モデル Female or male nu/nu mice bearing NCI-H441,or DLD-1, or MDA-MB-231
製剤
投薬量 12.5 mg/kg/day, 25 mg/kg/day, and 50 mg/kg/day
投与方法 Administered via p.o.

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

SpeciesMouseRatRabbitGuinea pigHamsterDogMonkeyBaboon
Weight (kg)0.020.151.80.40.0810312
Body Surface Area (m2)0.0070.0250.150.050.020.50.240.6
Km factor361285201220
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

参考

化学情報

Download Crizotinib (PF-02341066) SDF
分子量 450.34
化学式

C21H22Cl2FN5O

CAS No. 877399-52-5
保管 2年-20℃
6月-80℃in solvent
別名 N/A
溶解度 (25°C) * In vitro DMSO 9 mg/mL (19.98 mM)
<1 mg/mL (<1 mM)
エタノール <1 mg/mL (<1 mM)
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.
化学名 3-((R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)pyridin-2-amine

カスタマーフィードバック (8)


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Rating
Source Nat Med , 2011, 17, 1116-1120. Crizotinib (PF-02341066) purchased from Selleck
Method Western blot
Cell Lines RCT-E565 transplanted tumors
Concentrations 25 mg/kg/d, 50 mg/kg/d
Incubation Time 0-21 d
Results We then treated mice bearing RCT-E565 tumor transplants with PF02341066, a c-Met inhibitor currently in clinical development. PF02341066 abrogated both p-Akt and p-S6RP signals as well as tumor growth.

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Source Cancer Cell , 2011, 19, 679–690. Crizotinib (PF-02341066) purchased from Selleck
Method Cell Growth Inhibition Assay
Cell Lines Ba/F3 cells
Concentrations
Incubation Time 48 h
Results The sensitivities of L1196M-driven Ba/F3 cell clones to PF-02341066 were lower, closely resembling that of the Ba/F3 parental cells. The therapeutic indexes of CH5424802 and PF-02341066, the IC50 ratio of EML4-ALK L1196M-driven cell clones to the parental cells, were 7- to 12-fold and 1- to 2-fold.

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Source Cancer Cell , 2011, 19, 679–690. Crizotinib (PF-02341066) purchased from Selleck
Method Immunoblot analysis, Tumor growth inhibition Assay
Cell Lines xenograft models
Concentrations 100 mg/kg
Incubation Time 8 days
Results We showed that administration of CH5424802 led to significant tumor regression against both native EML4-ALK- and L1196M-driven tumors. On the other hand, PF-02341066 (100 mg/kg) resulted in no significant tumor growth inhibition against L1196M-driven tumors. Furthermore, we confirmed that phospho-STAT3, one of the downstream targets of ALK, was abolished in both tumors that were treated with CH5424802.

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Source J Biomol Screen , 2011, 16, 141-154. Crizotinib (PF-02341066) purchased from Selleck
Method VimPro-Fluc-MDA-MB-231 spheroid viability, Western blot
Cell Lines MDA-MB-231 spheroids
Concentrations
Incubation Time
Results When Vimpro-Fluc downregulation reaches ≥70%, then downregulation of vimentin protein expression is more pronounced. of the modulators tested—U0126, dasatinib,axitinib, and pF2341066-all downregulated Vimpro-Fluc activity by ≥70%, which correlated with a significant down-reglation of vimentin protein expression. Finally, dose-response curves were generated with both U0126 (iC50 = 2.5 µM) and axitinib (iC50 = 0.25 µM), demonstrating that these small molecules modulate Vimpro-Fluc activity in a dose-dependent manner, indicating that their respective target(s) and signaling pathways play a significant role in maintaining vimentin expression and possibly mesenchymal homeostasis (Fig. B)

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Rating
Source J Biomol Screen , 2011, 16, 141-154. Crizotinib (PF-02341066) purchased from Selleck
Method Secondary assay
Cell Lines MDA-MB-231 spheroids
Concentrations 10 µM
Incubation Time
Results U0126, pF2341066, axitinib, and pKC412 caused significant inhibition of the invasive potential of Mda-Mb-231 spheroids. Conversely, dasatinib, a potent inhibitor of vimentin gene expression, did not significantly alter the invasive potential of Mda-Mb-231 spheroids.

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Source Int J Proteomics , 2011, 2011, 215496. Crizotinib (PF-02341066) purchased from Selleck
Method CEER assay
Cell Lines H1993 cell line
Concentrations 0-10 μM
Incubation Time 4 h
Results In the c-MET amplified cell line H1993, activation of this pathway was blocked by the treatment with PF-2341066, a c-MET kinase inhibitor.

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Source Int J Proteomics, 2011, 2011, Article ID 215496. Crizotinib (PF-02341066) purchased from Selleck
Method Nikon inverted-phase microscope
Cell Lines lung tumor cell lines
Concentrations 0.1/1 µM
Incubation Time two weeks
Results Large colony formation of H1993 cells, whose proliferation in tissue culture was potently blocked by treatment with the c-MET kinase inhibitor PF-2341066, was also inhibited by treatment with the same inhibitor.

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Rating
Source Dr. Zhang of Tianjin Medical University. Crizotinib (PF-02341066) purchased from Selleck
Method Western blot
Cell Lines MDA-MB-231 cell line
Concentrations 0-100 nM
Incubation Time
Results

文献中の引用 (65)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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