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

高品質保証

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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 NFrSWYxEgXSxdH;4bYMhSXO|YYm= NGS1bos1QCCq Mo[1SG1UVw>? NFnndG1EgXSxdH;4bYNqfHliYXfhbY5{fCCvb4Xz[UBDSUZ|IHPlcIx{KGW6cILld5NqdmdiQVzLJGYyOTd2TDDteZRidnRiY3;lfJBz\XO|aX7nJGVOVDRid3n0bEBKSzVyIH;mJFAvPjJizszN MXWyNVU4OjV6OR?=
BAF3 M1;ScGN6fG:2b4jpZ{BCe3OjeR?= NHzzcZI1QCCq NE\SeGRFVVOR NHf5bZFEgXSxdH;4bYNqfHliYXfhbY5{fCCvb4Xz[UBDSUZ|IHPlcIx{KGW6cILld5NqdmdiQVzLJGwyOTl4TTDteZRidnRiY3;lfJBz\XO|aX7nJGVOVDRid3n0bEBKSzVyIH;mJFIvOiEQvF2= M2O0XFIyPTd{NUi5
BAF3 NXyzeG02S3m2b4TvfIlkKEG|c3H5 NFHDXZA1QCCq MonySG1UVw>? MkX1R5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmFHOyClZXzsd{BmgHC{ZYPzbY5oKEWPTEStRWxMKHerdHigTWM2OCCxZjCwMlI5KM7:TR?= MUmyNVU4OjV6OR?=
Kelly Mn3yR5l1d3SxeHnjJGF{e2G7 MnLjSG1UVw>? MVvDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDL[YxtgSClZXzsd{BmgHC{ZYPzbY5oKEGOSzDGNVE4PExibYX0ZY51KHerdHigTWM2OCCxZjCwMlQzKM7:TR?= M1;JXFIyPTd{NUi5
SH-SY5Y NWjPXnRJS3m2b4TvfIlkKEG|c3H5 MXzEUXNQ MXvDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDTTE1UYTW\IHPlcIx{KGW6cILld5NqdmdiQVzLJGYyOTd2TDDteZRidnRid3n0bEBKSzVyIH;mJFAvPTNizszN NVXTcI5ROjF3N{K1PFk>
SMS-KCN M3nZV2N6fG:2b4jpZ{BCe3OjeR?= MYnEUXNQ MULDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDTUXMuU0OQIHPlcIx{KGW6cILld5NqdmdiQVzLJHIyOjd3UTDteZRidnRid3n0bEBKSzVyIH;mJFAvQTFizszN M{XwVVIyPTd{NUi5
BAF3 MojNR5l1d3SxeHnjJGF{e2G7 MlzNOFghcA>? M2HUVWROW09? MVHDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRWY{KGOnbHzzJIV5eHKnc4PpcochXGWuLVHMT{B4cXSqIFnDOVAhd2ZiMD6xPUDPxE1? NVPjN5dXOjF3N{K1PFk>
3T3 MV\GeY5kfGmxbjDBd5NigQ>? MlTCNUBp M2XjeGROW09? M3\UNmlvcGmkaYTpc44hd2ZiUl;OJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iByLkC4JO69VQ>? MUeyNVgyOjRzNB?=
3T3-E NVTkVpRyTnWwY4Tpc44hSXO|YYm= MX6xJIg> Ml65SG1UVw>? M1exU2lvcGmkaYTpc44hd2ZiVFnFNkBie3Onc4Pl[EBoem:5dHig[oFkfG:{LXnu[JVk\WRiYYX0c5Bpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOC52NEig{txO MUiyNVgyOjRzNB?=
A549 NWHJO|RSU2mwYYPlJGF{e2G7 NX;ZT29pOSCq M{XHZmROW09? Mo\ZTY5pcWKrdHnvckBw\iCqdX3hckBz\WOxbXLpcoFvfCClLV3FWEBscW6jc3Wg[ZhxemW|c3XkJIF{e2W|c3XkJIF{KGmwaHnibZRqd25ib3[gTGdHNWmwZIXj[YQh[XW2b4Doc5NxcG:{eXzheIlwdiC5aYToJGlEPTBib3[gNE4xODhizszN NEnK[VEzOThzMkSxOC=>
BAF3-BCL MXTGeY5kfGmxbjDBd5NigQ>? Ml3WNUBp M2HOXmROW09? NETsb4ZKdmirYnn0bY9vKG:oIFHCUEBie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMT6xOVkh|ryP M4HadVIyQDF{NEG0
HEK293 MnXvSpVv[3Srb36gRZN{[Xl? M{i0ZlEhcA>? M2O1S2ROW09? NUH0NFYzUW6qaXLpeIlwdiCxZjDBXGwh[XO|ZYPz[YQh[XNiZ4Lve5RpKG[jY4Tvdk1qdmS3Y3XkJIF2fG:yaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIECuNlk1KM7:TR?= NIXSZmYzOThzMkSxOC=>
HEK293 NHizO5hHfW6ldHnvckBCe3OjeR?= M2rPSVEhcA>? MVHEUXNQ MVXJcohq[mm2aX;uJI9nKEmUIHHzd4V{e2WmIHHzJIdzd3e2aDDmZYN1d3JvaX7keYNm\CCjdYTvdIhwe3Cqb4L5cIF1cW:wIIfpeIghUUN3MDDv[kAzNjh6NzFOwG0> Mlq3NlE5OTJ2MUS=
Jurkat NEe1ZmRHfW6ldHnvckBCe3OjeR?= NFnxOm8yKGh? NUjD[ZZbTE2VTx?= NFzYSpZKdmirYnn0bY9vKG:oIFzDT{Bie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMj63OFEh|ryP MmfsNlE5OTJ2MUS=
KARPAS299 M{KzTGtqdmG|ZTDBd5NigQ>? M4r3bVEhcA>? M3zsUWROW09? NHfJ[o5KdmirYnn0bY9vKG:oIFHMT{Bie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6wNkDPxE1? MoHWNlE5OTJ2MUS=
PAE NVW4Rol[TnWwY4Tpc44hSXO|YYm= MkfqNUBp MXXEUXNQ NH64PZpKdmirYnn0bY9vKG:oIGTST2Ih[XO|ZYPz[YQh[XNiZ4Lve5RpKG[jY4Tvdk1qdmS3Y3XkJIF2fG:yaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIECuN|k6KM7:TR?= NXHhO452OjF6MUK0NVQ>
BAF3 MkPoSpVv[3Srb36gRZN{[Xl? MkX6Nk0{KGR? NXqzN2VVTE2VTx?= NXPWO2VGUW6qaXLpeIlwdiCxZjDUSWwu\nW|ZXSgbY5{fWyrbjDy[YNmeHSxcjDlfJBz\XO|ZXSge4l1cCCLQ{WwJI9nKDFwNkSzJO69VQ>? MnvYNlM4PDJ{NUK=
KARPAS299 NHfMeWpEgXSxdH;4bYMhSXO|YYm= M1jBbVIuOyCm MlOwSG1UVw>? MkTXTWM2OD1yLkC2OFIh|ryP MViyN|c1OjJ3Mh?=
EBC1 NGnHUmVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVO3NkBp M1\ueGROW09? M{jHfWlEPTB;MD6wNlMh|ryP NYf3XG1DOjN7OUOzNlg>
HCT116 M3vCPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3vxelczKGh? Mnn6SG1UVw>? MkG0TWM2OD1zND64NkDPxE1? MYOyN|k6OzN{OB?=
MCF7 M3LwSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MW[3NkBp M3X6XWROW09? Mlz4TWM2OD17LkW4JO69VQ>? NGnZU|MzOzl7M{OyPC=>
MDA-MB-231 NV7XdlFtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYDsRnhDPzJiaB?= M1TUV2ROW09? M3rHUGlEPTB;MUCuPEDPxE1? MnuxNlM6QTN|Mki=
MKN45 NEDUSpFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVLmRnpLPzJiaB?= NFjjZZBFVVOR MXPJR|UxRTBwMEGzJO69VQ>? MnruNlM6QTN|Mki=
NCI-H441 MoD2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGjJd2s4OiCq NETtTpNFVVOR NU\KS5FWUUN3ME2xO{4zPSEQvF2= MkOyNlM6QTN|Mki=
NCI-H661 M1K1PWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmfSO|IhcA>? NGnMeY5FVVOR NUjONXJKUUN3ME2xNU41PyEQvF2= MWWyN|k6OzN{OB?=
SK-MEL-28 M4HUSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGnIfZY4OiCq MojHSG1UVw>? NX:0epQ3UUN3ME2xNE46PyEQvF2= MWOyN|k6OzN{OB?=
SKOV3 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkXMO|IhcA>? M2LtVGROW09? M1XJb2lEPTB;MUKuPFUh|ryP MWCyN|k6OzN{OB?=
SNU5 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn3EO|IhcA>? NGLSVJRFVVOR NFXDUWlKSzVyPUCuNFE3KM7:TR?= MkTnNlM6QTN|Mki=
NCI-H2228 M2LSU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXHwdFZVPzJiaB?= NHPlRopFVVOR NHrJW2NKdmirYnn0bY9vKG:oIFHMT{1nfXOrb36g[JJqfmWwIHPlcIwheHKxbHnm[ZJifGmxbjD3bZRpKEmFNUCgc4YhOC5zMUig{txO NEniOpYzPDR|MkmwPS=>
NCI-H3122 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2\sblczKGh? MU\EUXNQ NE[wdWNKdmirYnn0bY9vKG:oIFHMT{1nfXOrb36g[JJqfmWwIHPlcIwheHKxbHnm[ZJifGmxbjD3bZRpKEmFNUCgc4YhOC5zMEig{txO MV6yOFQ{OjlyOR?=
NCI-H3122 MnrhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX63NkBp NFXzNmZFVVOR NH3ybZJKdmirYnn0bY9vKG:oIFHMT{1nfXOrb36g[JJqfmWwIHPlcIwheHKxbHnm[ZJifGmxbjDpckBpfW2jbjDOR2kuUDNzMkKgZ4VtdHNiaHHyZo9zcW6pIFHMT{BIOTJ4OVGgcZV1[W62IIfpeIghUUN3MDDv[kAxNjZ{MzFOwG0> NIPUPHQzPDR|MkmwPS=>
NCI-H3122 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEf2OlA4OiCq NXLXUmZzTE2VTx?= MWTJcohq[mm2aX;uJI9nKEGOSz3meZNqd25iZILpeoVvKGOnbHygdJJwdGmoZYLheIlwdiCrbjDoeY1idiCQQ1mtTFMyOjJiY3XscJMhcGG{Yn;ybY5oKEGOSzDMNVE6Pk1ibYX0ZY51KHerdHigTWM2OCCxZjCwMlg{QCEQvF2= MVeyOFQ{OjlyOR?=
NIH-3T3 M1\OeWtqdmG|ZTDBd5NigQ>? NWDSfFRwOSCq M3e3[mROW09? M1;nZmlvcGmkaYTpc44hd2ZiaIXtZY4hf2muZDD0fZBmKEWPTESt[pV{\WRiQVzLJIV5eHKnc4Pl[EBie3Onc4Pl[EBieyCyaH;zdIhwenmuYYTl[EBCVEtibHX2[Ywhf2m2aDDJR|UxKG:oIECuNFgh|ryP NX[0OYpzOjR2M{K5NFk>
NIH-3T3 M3;4XGtqdmG|ZTDBd5NigQ>? NX\QOXd6OSCq NYnpZ3VkTE2VTx?= Mo\GTY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzDHNVI3QUFibYX0ZY51KGW6cILld5Nm\CCjc4Pld5Nm\CCjczDwbI9{eGixLVHMT{Bt\X[nbDD3bZRpKEmFNUCgc4YhOC54MEWg{txO M3[3[FI1PDN{OUC5
NIH-3T3 MnPoT4lv[XOnIFHzd4F6 Mn35NUBp MV\EUXNQ M2LiNWlvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugV|EzOD[\IH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDBwNkK2JO69VQ>? M1fCdVI1PDN{OUC5
NIH-3T3 NUD3T4E6U2mwYYPlJGF{e2G7 MYOxJIg> MV7EUXNQ NF;4Z|ZKdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJGwyOTl4TTDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLki0N{DPxE1? M1S1blI1PDN{OUC5
NIH-3T3 MUXLbY5ie2ViQYPzZZk> NWHxcnhsOSCq NWPs[nNHTE2VTx?= MYPJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIFyxNVUzWiCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAyNjB{NjFOwG0> MkLPNlQ1OzJ7MEm=
BAF3 M1H0O2Z2dmO2aX;uJGF{e2G7 NYK4V3B{PzJiaB?= M3zVUGROW09? NGTxW2tKdmirYnn0bY9vKG:oIF7QUU9CVEtidILhcpNn\WO2ZXSgZZN{\XO|ZXSgZZMh[2WubDDndo94fGhiaX7obYJqfGmxbjD3bZRpKEmFNUCgc4YhOC5yNUGg{txO M4foUlI1PDZ6NkOy
BAF3 MXTDfZRwfG:6aXOgRZN{[Xl? NY\LXINSPzJiaB?= MW\EUXNQ NYfESJNMUUN3ME2wMlk5KM7:TR?= MUCyOFQ3QDZ|Mh?=
NIH-3T3 M37wXGtqdmG|ZTDBd5NigQ>? Mny3NUBp MXrJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIF[xNVc1VCCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAxNjF4NTFOwG0> NFrTcHczPDhzOUGxOi=>
NIH-3T3 MWHLbY5ie2ViQYPzZZk> M17ySVEhcA>? NYfLPFl1UW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BEOTF3NmmgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMD60O|gh|ryP NV2zcIdPOjR6MUmxNVY>
NIH-3T3 MmLHT4lv[XOnIFHzd4F6 M{\KXFEhcA>? MnjXTY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzDHNVIxOlJibYX0ZY51KGW6cILld5Nm\CCjc4Pld5Nm\CCjczDwbI9{eGixLVHMT{Bt\X[nbDD3bZRpKEmFNUCgc4YhOS5zNEig{txO M2qzSVI1QDF7MUG2
NIH-3T3 MkOzT4lv[XOnIFHzd4F6 M{TuWlEhcA>? M1L3NWlvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugNVE2OVSrboOgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMz6wN|kh|ryP NEHXc5czPDhzOUGxOi=>
KARPAS299 M{DNcmtqdmG|ZTDBd5NigQ>? MVq5NEBucW5? NHv6VnJFVVOR NXXrTHBoUW6qaXLpeIlwdiCxZjDOVG0u\nW|ZXSgRWxMKHCqb4PwbI9zgWyjdHnvckBmgHC{ZYPz[YQhf2m2aDDJR|UxKG:oIECuNVEh|ryP M4jFc|I1QTByN{Ww
MKN 45 NWfOS2xYU2mwYYPlJGF{e2G7 NYrldVVkOSCq NFXWXWZFVVOR NGW0WVVKdmirYnn0bY9vKG:oIHOtUYV1KHCqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6wNkDPxE1? NHXqb4YzPDlyMEe1NC=>
A549 M3XQeGN6fG:2b4jpZ{BCe3OjeR?= NFPRNIU1QCCq MlfzSG1UVw>? MUXJR|UxKG:oIESuNFg1KM7:TR?= M2\EeFI1QTByOEOw
NCI-H1975 MorDR5l1d3SxeHnjJGF{e2G7 MXO0PEBp NULJZpZOTE2VTx?= NV7zUXIzUUN3MDDv[kA4NjV3MTFOwG0> MUmyOFkxODh|MB?=
NCI-H1993 MWrDfZRwfG:6aXOgRZN{[Xl? MofOOFghcA>? NEfmR2NFVVOR M2HueWlEPTBib3[gNE4xPjFizszN NHXwVFkzPDlyMEizNC=>
NCI-H1993 M2jnPGFxd3Sxc3nzJGF{e2G7 MWexJO69VQ>? MXKyOEBp M3nwbGROW09? MW\kc4V{KG6xdDDpcoR2[2ViYYDvdJRwe2m| MmjYNlQ6ODB6M{C=
NIH-3T3 M2TUcGN6fG:2b4jpZ{BCe3OjeR?= M2S3XFQ5KGh? M{O0cGROW09? MonoTWM2OCCxZjCwMlM3PCEQvF2= NXnPO|NROjR7MEC4N|A>
EBC1 NYTjSZRiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIrpdVk4OiCq MkXTSG1UVw>? MYPJR|UxKG:oIECuNFA3QSEQvF2= NWOyS|R3OjR7MEC4N|E>
KARPAS299 M4LxT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHvmXZI4OiCq Mn3lSG1UVw>? NYHIPFNjUUN3MDDv[kAxNjJizszN NULCXZc{OjR7MEC4N|E>
NB1 NGDCeWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2nscWlEPTB;OUGuPVghdk1? NH;tNmtUSU6JRWK=
NCI-SNU-5 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUf1cIUzUUN3ME2xNFUvPzVibl2= M124RnNCVkeHUh?=
SR NUj6V4lST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NW\QNVNnUUN3ME2xNlYvOzFibl2= M4e4dHNCVkeHUh?=
SF539 NWDxO5NqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MojETWM2OD1{MESuNlQhdk1? NV;Pbo9UW0GQR1XS
SU-DHL-1 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1TCWmlEPTB;M{O2MlgzKG6P M4DUTHNCVkeHUh?=
SCC-3 MnnUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYfHd254UUN3ME2zOVYvPzZibl2= NGDPbGlUSU6JRWK=
DEL MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXTJR|UxRTN4OT65JI5O M{DienNCVkeHUh?=
CTV-1 MlPnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVzJR|UxRTV7Nj60PEBvVQ>? NUDYUYE{W0GQR1XS
EM-2 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2PCV2lEPTB;NkCxMlM1KG6P NVezcGJkW0GQR1XS
MHH-CALL-2 M2\xNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHvUPFRKSzVyPU[4Nk42PyCwTR?= NEHFNnFUSU6JRWK=
KM12 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUTV[mhMUUN3ME23NFYvQSCwTR?= NEHSeJBUSU6JRWK=
KINGS-1 MknkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUnNfGoyUUN3ME23OFkvPzVibl2= NVTifHdQW0GQR1XS
MEG-01 MkHiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYLJR|UxRTh3Nz62OkBvVQ>? MlHPV2FPT0WU
BV-173 NGDZdHRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mk\NTWM2OD1zLkC1PVk4KM7:TR?= MV7TRW5ITVJ?
LAMA-84 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmfsTWM2OD1zLkO4NlgzKM7:TR?= NVzLdGQ1W0GQR1XS
KARPAS-299 Moe4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYnJR|UxRTFwNEC4OlEh|ryP MVvTRW5ITVJ?
K-562 NIrHdmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUnaRYNqUUN3ME2xMlczOjZ7IN88US=> Mn3ZV2FPT0WU
SK-LMS-1 Mk\pS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHPtUGxKSzVyPUGuO|Y5PjdizszN NHezcWJUSU6JRWK=
MOLT-16 NHHyTZNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUjJR|UxRTFwOUW1O|Uh|ryP NF;hbYxUSU6JRWK=
CMK MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFvCfYZKSzVyPUGuPVYyPTlizszN M1Swd3NCVkeHUh?=
ST486 MnjZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NU[2foZyUUN3ME2yMlQ{ODd|IN88US=> MWPTRW5ITVJ?
CI-1 M4X2V2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1;DXmlEPTB;Mj60PVY2QSEQvF2= NIjXU5dUSU6JRWK=
KP-N-RT-BM-1 NF7X[nhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXjJR|UxRTJwN{CxNlIh|ryP NFPIenpUSU6JRWK=
ALL-PO NULwVWlDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGnkdVZKSzVyPUOuNVgzODdizszN NFPhOZhUSU6JRWK=
KS-1 M{OxOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYPJR|UxRTNwMkGyNlUh|ryP NGHOT5ZUSU6JRWK=
Becker MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYfJR|UxRTRwMkO5N{DPxE1? NUTtXlZsW0GQR1XS
GDM-1 Mk\LS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWe1VllmUUN3ME20MlI1PjF5IN88US=> NYTrUJdsW0GQR1XS
BC-1 M1;hOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2DsdGlEPTB;ND60PVI4PyEQvF2= MVLTRW5ITVJ?
NB14 M3j6[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmrMTWM2OD12LkizOVI1KM7:TR?= MnTXV2FPT0WU
NOS-1 NHP0ZphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3TOdGlEPTB;NT6zN|g4PCEQvF2= NGTIS4RUSU6JRWK=
MZ1-PC MkHOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUDJR|UxRTVwOEKxOVEh|ryP MnK4V2FPT0WU
A498 NIPucmNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYXlNGNEUUN3ME22MlA5PDd|IN88US=> NES3WZJUSU6JRWK=
EW-16 NXyyRXV{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEn5e25KSzVyPU[uN|c4PzNizszN MWTTRW5ITVJ?
NALM-6 Mlf0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHHheZZKSzVyPU[uOlg{QDdizszN M{LUVHNCVkeHUh?=
EB-3 NEXHcI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF73bJZKSzVyPUeuNFczOzNizszN MWnTRW5ITVJ?
697 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVX5d3J2UUN3ME25MlI1OzJ7IN88US=> NF3ldIFUSU6JRWK=
Ramos-2G6-4C10 M3f6[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mnu0TWM2OD17LkW5PFQzKM7:TR?= MmDOV2FPT0WU
KNS-81-FD MnnqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MULJR|UxRTlwNkm2OVMh|ryP M4LGUnNCVkeHUh?=
HUTU-80 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYX1ZXprUUN3ME25Mlc1PjR{IN88US=> M17EPXNCVkeHUh?=
LS-411N MlPaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1G3WGlEPTB;MUCuNFU3PyEQvF2= MoGzV2FPT0WU
RPMI-8402 M17tTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHHyRnhKSzVyPUGwMlEyPiEQvF2= M4TH[HNCVkeHUh?=
KU812 NHzTSHRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3\ZO2lEPTB;MUCuNlk6OSEQvF2= MUTTRW5ITVJ?
EW-1 NFXiZVhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3\zOmlEPTB;MUCuOFQzPSEQvF2= M4W4cXNCVkeHUh?=
HC-1 NIn1VnVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NY\JSGJqUUN3ME2xNE41QDR2IN88US=> NIfWc29USU6JRWK=
NB69 M1fVdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVvJR|UxRTFyLkWwOFMh|ryP MorMV2FPT0WU
MFH-ino NEm3dmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEDOTIxKSzVyPUGwMlg{ODNizszN NWWzPG57W0GQR1XS
CCRF-CEM NXzCVJZPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnroTWM2OD1zMT61PVch|ryP M1HtPHNCVkeHUh?=
SK-N-DZ M1jGN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXXJR|UxRTF{LkC0N|Yh|ryP NHfqb3lUSU6JRWK=
NCI-H720 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoTNTWM2OD1zMj6xO|A2KM7:TR?= MlGwV2FPT0WU
HCC1187 MlruS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX6zb2o{UUN3ME2xNk4zODRzIN88US=> M2fzbXNCVkeHUh?=
IST-SL2 NGflPHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVvlVINGUUN3ME2xNk41QDd{IN88US=> M2K5SnNCVkeHUh?=
KE-37 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXzicYdYUUN3ME2xNk44QTZ4IN88US=> NXnDOoJVW0GQR1XS
HCC1599 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlXGTWM2OD1zMj65NFY6KM7:TR?= NUTuWXVRW0GQR1XS
A4-Fuk MmnaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{W5UmlEPTB;MUKuPVU5PiEQvF2= M2PqTXNCVkeHUh?=
NKM-1 MnT6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NW\s[2RjUUN3ME2xN{4zQTJ3IN88US=> NH7SfYlUSU6JRWK=
BE-13 NGrDU4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkDOTWM2OD1zMz63PVg6KM7:TR?= Mn3FV2FPT0WU
MV-4-11 NXX6SnRKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkHnTWM2OD1zND6wN|I1KM7:TR?= M3\rU3NCVkeHUh?=
OPM-2 MnfZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NI[0OlBKSzVyPUG0MlQxQDVizszN NXjpWZpyW0GQR1XS
KARPAS-422 NVjadoZxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4rhNGlEPTB;MUSuOVEzPiEQvF2= NHPFZ5dUSU6JRWK=
RPMI-8226 NXrxOJJCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1X3b2lEPTB;MUSuPFkyPSEQvF2= NULSTG4xW0GQR1XS
KARPAS-45 M3vqUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NET6VXdKSzVyPUG1Mlc4OTZizszN M3TvTXNCVkeHUh?=
SK-PN-DW MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYC5XppPUUN3ME2xOU45PjNzIN88US=> M1mxPHNCVkeHUh?=
LC-2 M1TZWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnfLTWM2OD1zNj6xOVA3KM7:TR?= MknkV2FPT0WU
NCI-H1648 NF;YdXVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mk\1TWM2OD1zNj6yOVQh|ryP NHH1TVFUSU6JRWK=
RL95-2 M2LURWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4LZfGlEPTB;MU[uN|k4QCEQvF2= MmT6V2FPT0WU
KNS-42 M3Xoc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEf0WFlKSzVyPUG2MlczPzRizszN NHSwV2RUSU6JRWK=
RPMI-6666 MmLDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnWzTWM2OD1zNj65NlEyKM7:TR?= M4L5XXNCVkeHUh?=
SIG-M5 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFrE[ZBKSzVyPUG3MlE6ODNizszN MlT4V2FPT0WU
VA-ES-BJ MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXzpU3hsUUN3ME2xO{44PDVzIN88US=> M3;CV3NCVkeHUh?=
MONO-MAC-6 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoW3TWM2OD1zNz65N|EzKM7:TR?= MnzqV2FPT0WU
LAN-6 Mlu5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4jwNGlEPTB;MUiuO|U2PyEQvF2= M4CwUXNCVkeHUh?=
A388 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NETnNHFKSzVyPUG5MlMxPTlizszN Mk\wV2FPT0WU
SK-NEP-1 M1znR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGDZe41KSzVyPUKwMlIyOzJizszN NE\uZldUSU6JRWK=
TE-10 MlfUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHzNS5lKSzVyPUKwMlUzOjFizszN MVTTRW5ITVJ?
HL-60 NEDXO2RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFnnS4VKSzVyPUKwMlkxQTlizszN MofsV2FPT0WU
MC116 MmL0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVvvcW1ZUUN3ME2yNU44OjJzIN88US=> M4\kOHNCVkeHUh?=
SW962 M2jsPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{LHNGlEPTB;MkGuO|kyPSEQvF2= M3zv[nNCVkeHUh?=
NOMO-1 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mkm0TWM2OD1{Mj62OVY1KM7:TR?= M{jiWnNCVkeHUh?=
CTB-1 NIPhOW1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEntU|BKSzVyPUKyMlg3PzFizszN NYr0NHpWW0GQR1XS
MRK-nu-1 NGK5bGlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXrvXlFVUUN3ME2yNk46ODd2IN88US=> NHjvVHZUSU6JRWK=
GR-ST NYrCXVhrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MU\JR|UxRTJ|Lke2JO69VQ>? NFvlVHlUSU6JRWK=
HH MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVXwfoJlUUN3ME2yOE4xODNizszN MXHTRW5ITVJ?
NCI-H1963 MkXBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF7ZVoNKSzVyPUK0MlA4QDJizszN NX\DTYhnW0GQR1XS
QIMR-WIL NHrjTYlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVTSUHNbUUN3ME2yOE45Pzd{IN88US=> NVfSOmF5W0GQR1XS
CGTH-W-1 NF7iNmJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3XmR2lEPTB;MkWuNFczOyEQvF2= MY\TRW5ITVJ?
LP-1 NVPTU497T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVjpdXo1UUN3ME2yOU43PTVzIN88US=> MXPTRW5ITVJ?
NCI-H748 M2D4dmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnTKTWM2OD1{Nj61NVM4KM7:TR?= MWjTRW5ITVJ?
PF-382 NGjIcIZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYSwZ5ZYUUN3ME2yO{4zOjJ|IN88US=> NHzlPFNUSU6JRWK=
ATN-1 MnS0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkH1TWM2OD1{Nz6zO|MzKM7:TR?= NFTQZo5USU6JRWK=
L-540 NHnsZZhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH;UWlFKSzVyPUK3MlY1PTlizszN MVrTRW5ITVJ?
LXF-289 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGiydJlKSzVyPUK3Mlc2OTlizszN MnPsV2FPT0WU
LS-513 NX\sRY9MT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX64NoRiUUN3ME2yPE4yQDB5IN88US=> MXTTRW5ITVJ?
NCI-H1581 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkG2TWM2OD1|MD6zPVc3KM7:TR?= M3rNUXNCVkeHUh?=
ES6 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYXRSpgyUUN3ME2zNE43QDl7IN88US=> MX7TRW5ITVJ?
SW982 NH3Je3dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYnJR|UxRTNyLki1OlYh|ryP MWPTRW5ITVJ?
DOHH-2 M17MW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlrjTWM2OD1|MT61PFk{KM7:TR?= MVnTRW5ITVJ?
DB NV\1O5VjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4LKVWlEPTB;M{OuPVQ{OSEQvF2= NXP0fIZNW0GQR1XS
MPP-89 NWq5VGFXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2XiNmlEPTB;M{SuNVc2PiEQvF2= NHXUOG9USU6JRWK=
LB831-BLC M{fPPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYTJR|UxRTN2LkWxPFQh|ryP MkDyV2FPT0WU
NB5 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4LWT2lEPTB;M{SuPFU{PSEQvF2= MXjTRW5ITVJ?
GB-1 NIHWPWtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{C5dWlEPTB;M{WuNFQ3QSEQvF2= NF;yV3hUSU6JRWK=
TE-15 NX7lZllNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYXJR|UxRTN3LkKyN|gh|ryP NUHmOWlTW0GQR1XS
LC4-1 NFGyfnpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV3JR|UxRTN3LkO4OFch|ryP NYLZbY1uW0GQR1XS
NCI-H747 NGjxZ3NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXnJR|UxRTN4LkGzOlkh|ryP M{jrWHNCVkeHUh?=
NTERA-S-cl-D1 MkDjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3m4NmlEPTB;M{iuO|M1PyEQvF2= M2\3TXNCVkeHUh?=
SK-MM-2 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFjJRVhKSzVyPUSwMlEyPDZizszN MX7TRW5ITVJ?
TGW Mo\yS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4W3N2lEPTB;NEGuNFU3OyEQvF2= MoDKV2FPT0WU
ONS-76 MlnBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEjBPYdKSzVyPUSyMlQ5QDNizszN NEXs[VNUSU6JRWK=
CPC-N MlXDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIrXRoxKSzVyPUSyMlk6PzFizszN NFrwT2dUSU6JRWK=
ES4 NX71OGJrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn:wTWM2OD12ND60NVU{KM7:TR?= MnXxV2FPT0WU
Daudi Ml3pS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{HhPWlEPTB;NEWuNFgzPyEQvF2= NHTTO4dUSU6JRWK=
MOLT-4 NUSwSmtQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmrRTWM2OD12NT6wPFU{KM7:TR?= MmrYV2FPT0WU
HT-144 M4KwdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYLRcHVHUUN3ME20Ok44OjZizszN NV7jWmROW0GQR1XS
SW872 NF;yN3VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoHUTWM2OD12OD6xPVM{KM7:TR?= NHW2ZpFUSU6JRWK=
D-283MED M4XWPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXToUpg2UUN3ME20PE4{PTR{IN88US=> MV;TRW5ITVJ?
NCI-H2126 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYDJR|UxRTR6Lki0O|Yh|ryP M3yyO3NCVkeHUh?=
NCI-SNU-16 Mmf1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1PJVGlEPTB;NEmuNlE1OyEQvF2= NULsS|JKW0GQR1XS
CESS MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlGxTWM2OD12OT61NFg5KM7:TR?= MULTRW5ITVJ?
A101D MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXvJR|UxRTR7Lkm3N|Yh|ryP NXixbZhzW0GQR1XS

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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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Rating
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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Rating
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 (64)

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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