Crizotinib (PF-02341066)

Pfizer辉瑞授权 目录号:S1068

Crizotinib (PF-02341066) Chemical Structure

Molecular Weight(MW): 450.34

Crizotinib (PF-02341066) 克唑替尼是一种有效的c-MetALK抑制剂,在细胞试验中IC50分别为11 nM 和 24 nM。它同时也是有效的ROS1抑制剂,其Ki值小于0.025 nM。

规格 价格 库存 购买数量  
In DMSO RMB 1812.55 现货
RMB 900.49 现货
RMB 1372.81 现货
RMB 4681.47 现货
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产品安全说明书

c-Met抑制剂选择性比较

生物活性

产品描述 Crizotinib (PF-02341066) 克唑替尼是一种有效的c-MetALK抑制剂,在细胞试验中IC50分别为11 nM 和 24 nM。它同时也是有效的ROS1抑制剂,其Ki值小于0.025 nM。
靶点
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
体外研究

PF-2341066作用于mIMCD3小鼠和MDCK犬上皮细胞,作用于c-Met磷酸化作用时具有相似效果,IC50分别为5 nM 和20 nM。PF-2341066作用于表达c-Met ATP-结合位点突变型V1092I 或H1094R或 P-环突变 M1250T 的NIH3T3 细胞,具有相似的活性,且活力增高,IC50分别为19 nM,2 nM 和15 nM,而作用于表达野生型受体的NIH3T3 细胞时,IC50为13 nM。[1] 相反, 观察到PF-2341066作用于表达c-Met活化环突变型Y1230C 和Y1235D的细胞时,与作用于野生型受体相比,效果发生显著改变,IC50分别为127 nM 和92 nM。PF-2341066 作用于分别表达内源性c-Met 突变体R988C和 T1010I 的NCI-H69 和HOP92 细胞,也有效抑制c-Met 磷酸化, IC50分别为13 nM 和16 nM。与作用于c-Met相比,PF-2341066作用于VEGFR2 和PDGFRβ RTKs, 选择性高1000多倍,作用于IRK和Lck选择性高250多倍,作用于Tie2, TrkA,和TrkB选择性高40到60倍。PF-2341066 作用于RON和 Axl RTKs时选择性为20到30倍。相反,PF-2341066 作用于表达ALK RTK 的核磷蛋白 (NPM)- 间变性淋巴瘤激酶(ALK) 致癌融合突变体和 KARPAS299人间变性大细胞淋巴瘤(ALCL)细胞系时具有相近的IC50值,为24 nM。PF-2341066抑制c-Met依赖的癌细胞的肿瘤表现型,和内皮细胞的血管生成表现型。PF-2341066抑制人GTL-16胃癌细胞生长,IC50为9.7 nM。PF-2341066诱导 GTL-16细胞凋亡,IC50 为8.4 nM。PF-2341066 抑制HGF刺激的人NCI-H441肺癌细胞迁移和入侵,IC50分别为11 nM 和6.1 nM。PF-2341066抑制 MDCK细胞散射,IC50为16 nM。PF-2341066 抑制HGF-刺激的c-Met磷酸化,细胞存活,和Matrigel入侵,IC50分别为11 nM, 14 nM和35 nM。此外, PF-2341066抑制纤维蛋白胶中的血清刺激的 HMVEC分支小管形成 (形成血管)。[1] PF-2341066 作用于Karpas299 或SU-DHL-1 ALCL细胞,也有效抑制 NPM-ALK磷酸化,IC50 为24 nM。PF-2341066 有效抑制细胞增殖,伴随着使细胞周期停在G(1)-S期,且诱导 ALK阳性的 ALCL 细胞凋亡,IC50为30 nM, 但是作用于ALK阴性的淋巴瘤细胞则无效果。 [2] 此外, PF-2341066 抑制骨肉瘤的一些活动行为,及其肿瘤生长 (例如,增殖和存活)和转移 (例如,入侵和形成克隆)。[3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BAF3 NEHLNplEgXSxdH;4bYMhSXO|YYm= NFHMSXY1QCCq NEPaRmdFVVOR M4KyeWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KG2xdYPlJGJCTjNiY3XscJMh\XiycnXzd4lv\yCDTFugSlEyPzSOIH31eIFvfCClb3X4dJJme3OrbnegSW1NPCC5aYToJGlEPTBib3[gNE43OiEQvF2= NWPhOJlPOjF3N{K1PFk>
BAF3 MUHDfZRwfG:6aXOgRZN{[Xl? M4jWW|Q5KGh? M{L6S2ROW09? NVvjNJJ5S3m2b4TvfIlkcXS7IHHnZYlve3RibX;1d4UhSkGIMzDj[YxteyCneIDy[ZN{cW6pIFHMT{BNOTF7Nl2gcZV1[W62IHPv[ZhxemW|c3nu[{BGVUx2IIfpeIghUUN3MDDv[kAzNjJizszN NUO4NG5oOjF3N{K1PFk>
BAF3 MYTDfZRwfG:6aXOgRZN{[Xl? MX:0PEBp MWnEUXNQ MWjDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRWY{KGOnbHzzJIV5eHKnc4PpcochTU2OND3BUGshf2m2aDDJR|UxKG:oIECuNlgh|ryP M1PCbVIyPTd{NUi5
Kelly NXXxR3lnS3m2b4TvfIlkKEG|c3H5 Ml3TSG1UVw>? MX7DfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDL[YxtgSClZXzsd{BmgHC{ZYPzbY5oKEGOSzDGNVE4PExibYX0ZY51KHerdHigTWM2OCCxZjCwMlQzKM7:TR?= NX3YXpZ6OjF3N{K1PFk>
SH-SY5Y MYPDfZRwfG:6aXOgRZN{[Xl? Ml:xSG1UVw>? MoHWR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV2guW1l3WTDj[YxteyCneIDy[ZN{cW6pIFHMT{BHOTF5NFygcZV1[W62IIfpeIghUUN3MDDv[kAxNjV|IN88US=> NEjS[mkzOTV5MkW4PS=>
SMS-KCN MlvXR5l1d3SxeHnjJGF{e2G7 MlTmSG1UVw>? MlW2R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV21UNUuFTjDj[YxteyCneIDy[ZN{cW6pIFHMT{BTOTJ5NWGgcZV1[W62IIfpeIghUUN3MDDv[kAxNjlzIN88US=> NYjZcFF6OjF3N{K1PFk>
BAF3 M1;jUWN6fG:2b4jpZ{BCe3OjeR?= MkLvOFghcA>? NHL6XI9FVVOR MXLDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRWY{KGOnbHzzJIV5eHKnc4PpcochXGWuLVHMT{B4cXSqIFnDOVAhd2ZiMD6xPUDPxE1? M1q1UlIyPTd{NUi5
3T3 M1fVRWZ2dmO2aX;uJGF{e2G7 MkXvNUBp NVPGT5Y3TE2VTx?= Mni4TY5pcWKrdHnvckBw\iCUT16gZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwMEig{txO MUiyNVgyOjRzNB?=
3T3-E M{jTPWZ2dmO2aX;uJGF{e2G7 M4ntfVEhcA>? NVjvXHZrTE2VTx?= NFLoc2ZKdmirYnn0bY9vKG:oIGTJSVIh[XO|ZYPz[YQh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwNES4JO69VQ>? NXf0RZFjOjF6MUK0NVQ>
A549 NYHwUIE{U2mwYYPlJGF{e2G7 NXLLPXhHOSCq NHPTeI9FVVOR Mn;hTY5pcWKrdHnvckBw\iCqdX3hckBz\WOxbXLpcoFvfCClLV3FWEBscW6jc3Wg[ZhxemW|c3XkJIF{e2W|c3XkJIF{KGmwaHnibZRqd25ib3[gTGdHNWmwZIXj[YQh[XW2b4Doc5NxcG:{eXzheIlwdiC5aYToJGlEPTBib3[gNE4xODhizszN MoO4NlE5OTJ2MUS=
BAF3-BCL MV\GeY5kfGmxbjDBd5NigQ>? M3\wPVEhcA>? MYXEUXNQ M2fKbWlvcGmkaYTpc44hd2ZiQVLMJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iBzLkG1PUDPxE1? MnPkNlE5OTJ2MUS=
HEK293 NF3nUpVHfW6ldHnvckBCe3OjeR?= NYfCdppQOSCq NWH6TG1ZTE2VTx?= MX3Jcohq[mm2aX;uJI9nKEG[TDDhd5Nme3OnZDDhd{Boem:5dHig[oFkfG:{LXnu[JVk\WRiYYX0c5Bpd3OyaH;yfYxifGmxbjD3bZRpKEmFNUCgc4YhOC5{OUSg{txO MnjHNlE5OTJ2MUS=
HEK293 M1i2OmZ2dmO2aX;uJGF{e2G7 NWrlO2JyOSCq MorvSG1UVw>? MXHJcohq[mm2aX;uJI9nKEmUIHHzd4V{e2WmIHHzJIdzd3e2aDDmZYN1d3JvaX7keYNm\CCjdYTvdIhwe3Cqb4L5cIF1cW:wIIfpeIghUUN3MDDv[kAzNjh6NzFOwG0> Mn24NlE5OTJ2MUS=
Jurkat Mn\NSpVv[3Srb36gRZN{[Xl? M1OyTVEhcA>? NWTZN|Q2TE2VTx?= M1fJVmlvcGmkaYTpc44hd2ZiTFPLJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iB{Lke0NUDPxE1? MnnjNlE5OTJ2MUS=
KARPAS299 M{XkUWtqdmG|ZTDBd5NigQ>? MWSxJIg> MWnEUXNQ MkH6TY5pcWKrdHnvckBw\iCDTFugZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwMEKg{txO Ml71NlE5OTJ2MUS=
PAE MVPGeY5kfGmxbjDBd5NigQ>? M1q1b|EhcA>? M1zBeWROW09? M1nkcWlvcGmkaYTpc44hd2ZiVGLLRkBie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6zPVkh|ryP MWmyNVgyOjRzNB?=
BAF3 MVnGeY5kfGmxbjDBd5NigQ>? MU[yMVMh\A>? MUnEUXNQ MlTxTY5pcWKrdHnvckBw\iCWRVyt[pV{\WRiaX7zeYxqdiC{ZXPldJRweiCneIDy[ZN{\WRid3n0bEBKSzVyIH;mJFEvPjR|IN88US=> M3TWN|I{PzR{MkWy
KARPAS299 M2O4fGN6fG:2b4jpZ{BCe3OjeR?= NEe5dnozNTNiZB?= MV7EUXNQ NELyfXJKSzVyPUCuNFY1OiEQvF2= NHjEdHozOzd2MkK1Ni=>
EBC1 MoiwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnLxO|IhcA>? NW\aPZNHTE2VTx?= NI\YV3pKSzVyPUCuNFI{KM7:TR?= M3vBfVI{QTl|M{K4
HCT116 M3Xqc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3n4WlczKGh? NUDodXB7TE2VTx?= NHvjWpdKSzVyPUG0MlgzKM7:TR?= M3nsT|I{QTl|M{K4
MCF7 MoLYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4PNXlczKGh? MVXEUXNQ MXvJR|UxRTlwNUig{txO NVrNRYNpOjN7OUOzNlg>
MDA-MB-231 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFfrN4M4OiCq NXriUnJHTE2VTx?= MkHnTWM2OD1zMD64JO69VQ>? MWCyN|k6OzN{OB?=
MKN45 M1nofGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYW3NkBp NGCzdZhFVVOR NYT0SYxuUUN3ME2wMlAyOyEQvF2= MYSyN|k6OzN{OB?=
NCI-H441 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXnaPFlPPzJiaB?= NEDPVWdFVVOR Mo\0TWM2OD1zNz6yOUDPxE1? MX[yN|k6OzN{OB?=
NCI-H661 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnHIO|IhcA>? NUHEeod2TE2VTx?= MljQTWM2OD1zMT60O{DPxE1? MXiyN|k6OzN{OB?=
SK-MEL-28 NX7qXZRiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmXaO|IhcA>? NIDmWHJFVVOR MVPJR|UxRTFyLkm3JO69VQ>? NYLHNo5JOjN7OUOzNlg>
SKOV3 MmHVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYLJ[mN4PzJiaB?= M2i4W2ROW09? NWS2TJV7UUN3ME2xNk45PSEQvF2= NVnwe|AxOjN7OUOzNlg>
SNU5 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NW\zNmJwPzJiaB?= MYHEUXNQ MljMTWM2OD1yLkCxOkDPxE1? NUfXTpBNOjN7OUOzNlg>
NCI-H2228 MoXGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEL4VZQ4OiCq NGG4PXhFVVOR M2PUe2lvcGmkaYTpc44hd2ZiQVzLMYZ2e2mxbjDkdol3\W5iY3XscEBxem:uaX\ldoF1cW:wIIfpeIghUUN3MDDv[kAxNjFzODFOwG0> MV6yOFQ{OjlyOR?=
NCI-H3122 MkCzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFfUZ484OiCq NWjY[YNMTE2VTx?= NVvaXZFHUW6qaXLpeIlwdiCxZjDBUGsu\nW|aX;uJIRzcX[nbjDj[YxtKHC{b3zp[oVz[XSrb36ge4l1cCCLQ{WwJI9nKDBwMUC4JO69VQ>? NELQb4kzPDR|MkmwPS=>
NCI-H3122 M2W2VWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGLvd3k4OiCq MYnEUXNQ NIjPbYVKdmirYnn0bY9vKG:oIFHMT{1nfXOrb36g[JJqfmWwIHPlcIwheHKxbHnm[ZJifGmxbjDpckBpfW2jbjDOR2kuUDNzMkKgZ4VtdHNiaHHyZo9zcW6pIFHMT{BIOTJ4OVGgcZV1[W62IIfpeIghUUN3MDDv[kAxNjZ{MzFOwG0> NWjzbVJMOjR2M{K5NFk>
NCI-H3122 MnLWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWHYcG1kPzJiaB?= MXTEUXNQ M2HpfGlvcGmkaYTpc44hd2ZiQVzLMYZ2e2mxbjDkdol3\W5iY3XscEBxem:uaX\ldoF1cW:wIHnuJIh2dWGwIF7DTU1JOzF{MjDj[YxteyCqYYLic5JqdmdiQVzLJGwyOTl4TTDteZRidnRid3n0bEBKSzVyIH;mJFAvQDN6IN88US=> NV6wbYFyOjR2M{K5NFk>
NIH-3T3 Ml\CT4lv[XOnIFHzd4F6 Mom4NUBp MkjmSG1UVw>? M1jNcGlvcGmkaYTpc44hd2ZiaIXtZY4hf2muZDD0fZBmKEWPTESt[pV{\WRiQVzLJIV5eHKnc4Pl[EBie3Onc4Pl[EBieyCyaH;zdIhwenmuYYTl[EBCVEtibHX2[Ywhf2m2aDDJR|UxKG:oIECuNFgh|ryP M2P6clI1PDN{OUC5
NIH-3T3 Mli0T4lv[XOnIFHzd4F6 MYexJIg> NIDrO|NFVVOR MW\Jcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIFexNlY6SSCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAxNjZyNTFOwG0> MWGyOFQ{OjlyOR?=
NIH-3T3 MYnLbY5ie2ViQYPzZZk> MY[xJIg> M3X5UmROW09? NULlNXB5UW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BUOTJyNmmgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMD62NlYh|ryP MXqyOFQ{OjlyOR?=
NIH-3T3 M3yzZmtqdmG|ZTDBd5NigQ>? NInDbXoyKGh? M17jTWROW09? Mn7iTY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzDMNVE6Pk1ibYX0ZY51KGW6cILld5Nm\CCjc4Pld5Nm\CCjczDwbI9{eGixLVHMT{Bt\X[nbDD3bZRpKEmFNUCgc4YhOC56NEOg{txO NGf6VoIzPDR|MkmwPS=>
NIH-3T3 NIm2T|dMcW6jc3WgRZN{[Xl? MYqxJIg> MUPEUXNQ NWLMT4ZwUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BNOTF3MmKgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMT6wNlYh|ryP MVWyOFQ{OjlyOR?=
BAF3 MV\GeY5kfGmxbjDBd5NigQ>? NInjSJc4OiCq NVL2[Hc3TE2VTx?= NGL5fVVKdmirYnn0bY9vKG:oIF7QUU9CVEtidILhcpNn\WO2ZXSgZZN{\XO|ZXSgZZMh[2WubDDndo94fGhiaX7obYJqfGmxbjD3bZRpKEmFNUCgc4YhOC5yNUGg{txO NYDyOVM2OjR2Nki2N|I>
BAF3 M1T1VWN6fG:2b4jpZ{BCe3OjeR?= MnT6O|IhcA>? M13ZWGROW09? Mn7STWM2OD1yLkm4JO69VQ>? MmPVNlQ1Pjh4M{K=
NIH-3T3 MWDLbY5ie2ViQYPzZZk> NVP3cYNkOSCq NETyPXNKdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJGYyOTd2TDDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLkG2OUDPxE1? NV3CVIdXOjR6MUmxNVY>
NIH-3T3 NIDDellMcW6jc3WgRZN{[Xl? MXGxJIg> MWjJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIFOxNVU3YSCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAxNjR5ODFOwG0> NYHPdI5KOjR6MUmxNVY>
NIH-3T3 NIDvUHBMcW6jc3WgRZN{[Xl? MoXXNUBp MXvJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIFexNlAzWiCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAyNjF2ODFOwG0> NIPM[mszPDhzOUGxOi=>
NIH-3T3 MUfLbY5ie2ViQYPzZZk> M4fDZVEhcA>? NV25[ItTUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{AyOTVzVHnud{BufXSjboSg[ZhxemW|c3XkJIF{e2W|c3XkJIF{KHCqb4PwbI8uSUyNIHzleoVtKHerdHigTWM2OCCxZjCzMlA{QSEQvF2= M4TERVI1QDF7MUG2
KARPAS299 NEHGN5hMcW6jc3WgRZN{[Xl? NI\YW2I6OCCvaX6= MUTEUXNQ M{nEWGlvcGmkaYTpc44hd2ZiTmDNMYZ2e2WmIFHMT{BxcG:|cHjvdplt[XSrb36g[ZhxemW|c3XkJJdqfGhiSVO1NEBw\iByLkGxJO69VQ>? M1K1[|I1QTByN{Ww
MKN 45 NHXmZm1McW6jc3WgRZN{[Xl? MlHZNUBp NIrhZolFVVOR MkThTY5pcWKrdHnvckBw\iClLV3leEBxcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwMEKg{txO NH7lZlgzPDlyMEe1NC=>
A549 MXrDfZRwfG:6aXOgRZN{[Xl? NFe0ZpQ1QCCq M{jWOWROW09? Ml7XTWM2OCCxZjC0MlA5PCEQvF2= M2HZfFI1QTByOEOw
NCI-H1975 MUfDfZRwfG:6aXOgRZN{[Xl? NIjSTGk1QCCq MV;EUXNQ Ml\UTWM2OCCxZjC3MlU2OSEQvF2= Ml71NlQ6ODB6M{C=
NCI-H1993 NGntb|hEgXSxdH;4bYMhSXO|YYm= Mn\MOFghcA>? NUTQWWVoTE2VTx?= MmjmTWM2OCCxZjCwMlA3OSEQvF2= M3iyc|I1QTByOEOw
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NCI-SNU-16 NFvVXWxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MljtTWM2OD12OT6yNVQ{KM7:TR?= NVnmVW9nW0GQR1XS
CESS MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1LLfGlEPTB;NEmuOVA5QCEQvF2= MV3TRW5ITVJ?
A101D Mo[zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV;WPY03UUN3ME20PU46PzN4IN88US=> NF:0NnVUSU6JRWK=

... 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
体内研究

PF-2341066每天按50 mg/kg和75 mg/kg剂量处理GTL-16 模型, 引起大肿瘤 (体积大于600 mm3) 明显衰退,且按43天处理日程处理后,平均肿瘤体积降低60%。在另一项研究中, PF-2341066处理3个月以上,完全抑制GTL-16肿瘤生长,PF-2341066每天按50 mg/kg剂量处理小鼠,3个月后,只有1/12小鼠的肿瘤生长得到提高。PF-2341066每天按50 mg/kg剂量处理NCI-H441 NSCLC 模型处理周期为38天,观察到平均肿瘤体积降低43%。PF-2341066 每天按50 mg/kg剂量作用于 Caki-1 RCC模型,处理周期为33天,观察到平均肿瘤体积降低53%,且每种肿瘤体积降低至少30%。PF-2341066每天按 50 mg/kg剂量作用于 U87MG 恶性胶质瘤或PC-3前列腺癌移植瘤模型,几乎完全抑制肿瘤生长,在实验最后一天,抑制分别达97% 或84%。相反, PF-2341066每天按50 mg/kg剂量口服给药处理 MDA-MB-231 乳腺癌模型,或 DLD-1 结肠癌模型,不会显著抑制肿瘤生长。PF-2341066每天按12.5 mg/kg, 25 mg/kg, 和50 mg/kg剂量作用于 GTL-16 肿瘤,观察到CD31阳性内皮细胞显著降低,这种作用存在剂量依赖性,说明 MVD 受抑制,且具有相关的抗癌高效性,这种作用也存在剂量依赖性。PF-2341066 作用于GTL-16 和 U87MG 模型,显著降低人VEGFA 和IL-8血浆水平,这种作用存在剂量依赖性。PF-2341066口服处理GTL-16 肿瘤,观察到磷酸化的c-Met, Akt, Erk, PLCλ1,和 STAT5水平显著受抑制。[1]PF-2341066 每天按100 mg/kg剂量口服处理携带Karpas299 ALCL 移植瘤的SCID Beige 小鼠,具有抗癌高效性,这种作用存在剂量依赖性,处理15天,所有肿瘤完全衰退。此外, PF-2341066抑制关键NPM-ALK信号调节器, 包括磷脂酶C-γ, 信号转导器,及转录因子3, 细胞外信号调节激酶, 和Akt的激活剂,这些与 NPM-ALK 磷酸化和功能受抑制相关。[2] PF-2341066 抑制骨肉瘤的一些活动行为,及其肿瘤生长(例如, 增殖和存活)和转移 (例如,入侵和形成克隆)。PF-2341066口服饲喂裸鼠,抑制生长和相关的骨肉瘤裸鼠移植瘤的骨基质的形成。[3] PF-2341066 按50 mg/kg 剂量处理 c-MET-扩增的GTL-16移植瘤,引起肿瘤衰退,这与18F-FDG 摄取的缓慢降低相关,且降低葡糖糖转运蛋白 1, GLUT-1的表达。[4]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:

[1]

- 合并

生化激酶实验:

使用连续耦合的分光光度测定c-Met催化活性,通过分析NADH消耗率而测定c-Met诱导的ADP产量,这种作用具有时间依赖性。在 340 nm处使用分光光度法在指定时间点测定吸光值的降低而计算NADH的消耗量。为了测定Ki值, 在含实验试剂的实验孔中加入不同浓度PF-2341066,然后在37oC下温育10分钟。加入c-Met酶开始进行实验反应。
细胞实验:

[1]

- 合并
  • Cell lines: GTL-16胃癌细胞和T47D乳腺癌细胞
  • Concentrations: 0 nM-256 nM
  • Incubation Time: 1小时
  • Method:

    GTL-16胃癌细胞和T47D乳腺癌细胞接种在96孔板上,孔中含培养基,培养基中含10% 胎牛血清(FBS),然后转移到无血清培养基中[含0.04%牛血清蛋白(BSA)],处理 24小时。 在调查配体依赖的RTK 磷酸化实验中,加入相应的生长因子,处理20分钟。细胞和 PF-2341066和/或适当配体在指定时间温育1小时,然后使用含 1 mmol/L Na3VO4的HBSS冲洗细胞一次,然后从细胞中获得蛋白裂解物。随后,通过夹心酶联免疫吸附试验法使用特定的捕获抗体在96孔板上测定选定蛋白激酶的磷酸化,使用特点检测抗体测定磷酸化的酪氨酸残基。抗体包被的实验板(a) 在蛋白裂解物存在时,在4oC下过夜;(b)在溶于PBS的1% Tween-20 中冲洗7次;(c)在辣根过氧化物酶标记的抗总磷酸(PY-20)抗体(1:500)中温育20分钟;(d) 再次冲洗7次;(e)在3,3,5,5-四甲基联苯胺过氧化物酶底物中温育,开始显示反应,加入0.09 N H2SO4终止反应; (f)在450 nm 处使用分光光度计测定吸光度。


    (Only for Reference)
动物实验:

[1]

- 合并
  • Animal Models: 携带NCI-H441,或DLD-1,或MDA-MB-231的雌性和雄性nu/nu小鼠
  • Formulation: --
  • Dosages: 12.5 mg/kg/day, 25 mg/kg/day, 和50 mg/kg/day
  • Administration: 口服处理
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 9 mg/mL (19.98 mM)
Water Insoluble
Ethanol Insoluble
体内 从左到右依次将纯溶剂加入产品,现配现用(数据来自Selleck实验检测而非文献):
5% DMSO+30% PEG 300+dd H2O
5mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 450.34
化学式

C21H22Cl2FN5O

CAS号 877399-52-5
储存条件 粉状
溶于溶剂
别名 N/A

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
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 Recruiting 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
NCT02510001 Active not recruiting Drug: PF-02341066|Drug: PD-0325901|Drug: Binimetinib Solid Tumor|Colorectal Cancer University of Oxford|Queen''s University Belfast|Oxford University Hospitals NHS Trust|Velindre NHS Trust|University Hospital Antwerp|Hospital Vall d''Hebron|Saint Antoine University Hospital|European Georges Pompidou Hospital|Pfizer|University of Turin Italy|Belfast Health and Social Care Trust|Beaumont Hospital|European Commission|Array BioPharma|University of Paris 5 - Rene Descartes November 2014 Phase 1

技术支持

在订购、运输、储存和使用我们的产品的任何阶段,您遇到的任何问题,均可以通过拨打我们的热线电话400-668-6834,或者技术支持邮箱tech@selleck.cn,直接联系到我们。我们会在24小时内尽快联系您。

操作手册

如果有其他问题,请给我们留言。

  • * 必填项

常见问题及建议解决方法

  • 问题 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?

  • 回答:

    Our S1068 Crizotinib is R enantiomer(except batch 05 and 06, they are racemate), and S7505 is S enantiomer.

c-Met Signaling Pathway Map

c-Met Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID