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-Met和ALK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。

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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-Met和ALK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 NIPHOHpEgXSxdH;4bYMhSXO|YYm= NHr1eVU1QCCq M3LaTWROW09? NIThcVhEgXSxdH;4bYNqfHliYXfhbY5{fCCvb4Xz[UBDSUZ|IHPlcIx{KGW6cILld5NqdmdiQVzLJGYyOTd2TDDteZRidnRiY3;lfJBz\XO|aX7nJGVOVDRid3n0bEBKSzVyIH;mJFAvPjJizszN MXGyNVU4OjV6OR?=
BAF3 M1z1eWN6fG:2b4jpZ{BCe3OjeR?= Mo\wOFghcA>? MnPESG1UVw>? Mk\oR5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmFHOyClZXzsd{BmgHC{ZYPzbY5oKEGOSzDMNVE6Pk1ibYX0ZY51KGOxZYjwdoV{e2mwZzDFUWw1KHerdHigTWM2OCCxZjCyMlIh|ryP MYmyNVU4OjV6OR?=
BAF3 Mnu0R5l1d3SxeHnjJGF{e2G7 NHHRfIY1QCCq NYHJSJROTE2VTx?= MlHsR5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmFHOyClZXzsd{BmgHC{ZYPzbY5oKEWPTEStRWxMKHerdHigTWM2OCCxZjCwMlI5KM7:TR?= NUjHfnhzOjF3N{K1PFk>
Kelly NIHVSFFEgXSxdH;4bYMhSXO|YYm= NGLnVVVFVVOR NYrGW|ZbS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hU2WubImgZ4VtdHNiZYjwdoV{e2mwZzDBUGshTjFzN{TMJI12fGGwdDD3bZRpKEmFNUCgc4YhOC52MjFOwG0> MWKyNVU4OjV6OR?=
SH-SY5Y M3\lWGN6fG:2b4jpZ{BCe3OjeR?= M4TVO2ROW09? MnizR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV2guW1l3WTDj[YxteyCneIDy[ZN{cW6pIFHMT{BHOTF5NFygcZV1[W62IIfpeIghUUN3MDDv[kAxNjV|IN88US=> NHmwc3IzOTV5MkW4PS=>
SMS-KCN M{nWNGN6fG:2b4jpZ{BCe3OjeR?= MUTEUXNQ Mn22R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV21UNUuFTjDj[YxteyCneIDy[ZN{cW6pIFHMT{BTOTJ5NWGgcZV1[W62IIfpeIghUUN3MDDv[kAxNjlzIN88US=> NWrTbYpLOjF3N{K1PFk>
BAF3 MW\DfZRwfG:6aXOgRZN{[Xl? NU[1Z4tVPDhiaB?= M4f0bWROW09? M3HOWmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KG2xdYPlJGJCTjNiY3XscJMh\XiycnXzd4lv\yCWZXytRWxMKHerdHigTWM2OCCxZjCwMlE6KM7:TR?= NVXOeldjOjF3N{K1PFk>
3T3 NGHaWpVHfW6ldHnvckBCe3OjeR?= MUKxJIg> MVzEUXNQ MoLvTY5pcWKrdHnvckBw\iCUT16gZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwMEig{txO MUeyNVgyOjRzNB?=
3T3-E MlXDSpVv[3Srb36gRZN{[Xl? M{O3XlEhcA>? M1fTSWROW09? NEXVUGZKdmirYnn0bY9vKG:oIGTJSVIh[XO|ZYPz[YQh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwNES4JO69VQ>? MmC0NlE5OTJ2MUS=
A549 NF7rUI9McW6jc3WgRZN{[Xl? NGnQR|cyKGh? M4X5WmROW09? M1XVdWlvcGmkaYTpc44hd2ZiaIXtZY4hemWlb33ibY5idnRiYz3NSXQhc2mwYYPlJIV5eHKnc4Pl[EBie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGhITi2rbnT1Z4VlKGG3dH;wbI9{eGixconsZZRqd25id3n0bEBKSzVyIH;mJFAvODB6IN88US=> NWTFdJd5OjF6MUK0NVQ>
BAF3-BCL NX;zZ5psTnWwY4Tpc44hSXO|YYm= M{S4Z|EhcA>? M3X6NmROW09? M3Llc2lvcGmkaYTpc44hd2ZiQVLMJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iBzLkG1PUDPxE1? NF3vbJEzOThzMkSxOC=>
HEK293 MmnJSpVv[3Srb36gRZN{[Xl? M3nIVFEhcA>? MYfEUXNQ Ml\VTY5pcWKrdHnvckBw\iCDWFygZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwMkm0JO69VQ>? M{XPelIyQDF{NEG0
HEK293 NH\JToFHfW6ldHnvckBCe3OjeR?= NWrUc3hnOSCq NVLqeJZzTE2VTx?= NYH4WnltUW6qaXLpeIlwdiCxZjDJVkBie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMj64PFch|ryP MUeyNVgyOjRzNB?=
Jurkat NGKxRYxHfW6ldHnvckBCe3OjeR?= NXzVcmZxOSCq NYXJdZNsTE2VTx?= M17t[GlvcGmkaYTpc44hd2ZiTFPLJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iB{Lke0NUDPxE1? NF61[ngzOThzMkSxOC=>
KARPAS299 MUfLbY5ie2ViQYPzZZk> M2ntRVEhcA>? NX[x[|RRTE2VTx?= M3flW2lvcGmkaYTpc44hd2ZiQVzLJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iByLkCyJO69VQ>? MXiyNVgyOjRzNB?=
PAE M1X0NWZ2dmO2aX;uJGF{e2G7 NFzhdJMyKGh? MY\EUXNQ M4XVXmlvcGmkaYTpc44hd2ZiVGLLRkBie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6zPVkh|ryP MVGyNVgyOjRzNB?=
BAF3 MmPTSpVv[3Srb36gRZN{[Xl? MnWzNk0{KGR? M2fYemROW09? NV7sTYRsUW6qaXLpeIlwdiCxZjDUSWwu\nW|ZXSgbY5{fWyrbjDy[YNmeHSxcjDlfJBz\XO|ZXSge4l1cCCLQ{WwJI9nKDFwNkSzJO69VQ>? Mn34NlM4PDJ{NUK=
KARPAS299 MnjIR5l1d3SxeHnjJGF{e2G7 NWTGV2pEOi1|IHS= NYHoXIloTE2VTx?= M{XvXGlEPTB;MD6wOlQzKM7:TR?= M2DlcFI{PzR{MkWy
EBC1 NI\PTnpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1nIfFczKGh? Mk[4SG1UVw>? Mn;tTWM2OD1yLkCyN{DPxE1? NYeyfnBSOjN7OUOzNlg>
HCT116 M2rUPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXnF[od7PzJiaB?= M4nvSGROW09? MlLaTWM2OD1zND64NkDPxE1? MVOyN|k6OzN{OB?=
MCF7 M2LBe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYrDUmF6PzJiaB?= M4XkXmROW09? MnS1TWM2OD17LkW4JO69VQ>? MlzTNlM6QTN|Mki=
MDA-MB-231 NFjNXIlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{CxU|czKGh? MnT5SG1UVw>? NUK4VIZYUUN3ME2xNE45KM7:TR?= NW\5WHR6OjN7OUOzNlg>
MKN45 M3;kO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVu3NkBp Mn3qSG1UVw>? MYXJR|UxRTBwMEGzJO69VQ>? MU[yN|k6OzN{OB?=
NCI-H441 NIOxVWJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmfGO|IhcA>? MmDNSG1UVw>? Mn\5TWM2OD1zNz6yOUDPxE1? M3rQdFI{QTl|M{K4
NCI-H661 NGLVblhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NG\RZms4OiCq MmTTSG1UVw>? Mn60TWM2OD1zMT60O{DPxE1? NIrPR2MzOzl7M{OyPC=>
SK-MEL-28 NUP6W5lTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVz3WIZqPzJiaB?= NXjCfJZXTE2VTx?= MmG3TWM2OD1zMD65O{DPxE1? NFfCRVIzOzl7M{OyPC=>
SKOV3 M4jMNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlHPO|IhcA>? M122fmROW09? MVXJR|UxRTF{Lki1JO69VQ>? MXmyN|k6OzN{OB?=
SNU5 M3jENmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXK3NkBp MUTEUXNQ NHrXSGhKSzVyPUCuNFE3KM7:TR?= MXyyN|k6OzN{OB?=
NCI-H2228 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmnmO|IhcA>? MV7EUXNQ MknPTY5pcWKrdHnvckBw\iCDTFut[pV{cW:wIHTybZZmdiClZXzsJJBzd2yrZnXyZZRqd25id3n0bEBKSzVyIH;mJFAvOTF6IN88US=> MnPpNlQ1OzJ7MEm=
NCI-H3122 NF\uZ4ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml;vO|IhcA>? M2\3RWROW09? NHfUcXhKdmirYnn0bY9vKG:oIFHMT{1nfXOrb36g[JJqfmWwIHPlcIwheHKxbHnm[ZJifGmxbjD3bZRpKEmFNUCgc4YhOC5zMEig{txO NHfvOo8zPDR|MkmwPS=>
NCI-H3122 MnvTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3HJVFczKGh? NILSNGlFVVOR NV;HSIZHUW6qaXLpeIlwdiCxZjDBUGsu\nW|aX;uJIRzcX[nbjDj[YxtKHC{b3zp[oVz[XSrb36gbY4hcHWvYX6gUmNKNUh|MUKyJINmdGy|IHjhdoJwemmwZzDBUGshTzF{NknBJI12fGGwdDD3bZRpKEmFNUCgc4YhOC54MkOg{txO MWSyOFQ{OjlyOR?=
NCI-H3122 NXfGcWFiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWq3NkBp NHHibZZFVVOR M{O0d2lvcGmkaYTpc44hd2ZiQVzLMYZ2e2mxbjDkdol3\W5iY3XscEBxem:uaX\ldoF1cW:wIHnuJIh2dWGwIF7DTU1JOzF{MjDj[YxteyCqYYLic5JqdmdiQVzLJGwyOTl4TTDteZRidnRid3n0bEBKSzVyIH;mJFAvQDN6IN88US=> NH[4VpczPDR|MkmwPS=>
NIH-3T3 MmjpT4lv[XOnIFHzd4F6 MkjHNUBp MnPvSG1UVw>? MYLJcohq[mm2aX;uJI9nKGi3bXHuJJdqdGRidInw[UBGVUx2LX\1d4VlKEGOSzDlfJBz\XO|ZXSgZZN{\XO|ZXSgZZMheGixc4Doc5J6dGG2ZXSgRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLkC4JO69VQ>? M1zJUFI1PDN{OUC5
NIH-3T3 MnHQT4lv[XOnIFHzd4F6 Mme4NUBp MULEUXNQ NIHYV49KdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJGcyOjZ7QTDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLk[wOUDPxE1? M1Tac|I1PDN{OUC5
NIH-3T3 M4fCeGtqdmG|ZTDBd5NigQ>? M4XqfVEhcA>? NH\qdJdFVVOR NWDqVmVsUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BUOTJyNmmgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMD62NlYh|ryP NYDOUW9zOjR2M{K5NFk>
NIH-3T3 M1rkUmtqdmG|ZTDBd5NigQ>? M1q2c|EhcA>? NHuwW4NFVVOR M4jsVWlvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugUFEyQT[PIH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDBwOESzJO69VQ>? M2LH[|I1PDN{OUC5
NIH-3T3 MljuT4lv[XOnIFHzd4F6 NGHSOYoyKGh? MYXEUXNQ MkfrTY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzDMNVE2OlJibYX0ZY51KGW6cILld5Nm\CCjc4Pld5Nm\CCjczDwbI9{eGixLVHMT{Bt\X[nbDD3bZRpKEmFNUCgc4YhOS5yMk[g{txO NVLkem42OjR2M{K5NFk>
BAF3 NFLHW5ZHfW6ldHnvckBCe3OjeR?= M{XHVlczKGh? M{flcmROW09? NWPWdIVNUW6qaXLpeIlwdiCxZjDOVG0wSUyNIITyZY5{\mWldHXkJIF{e2W|c3XkJIF{KGOnbHyg[5Jwf3SqIHnubIljcXSrb36ge4l1cCCLQ{WwJI9nKDBwMEWxJO69VQ>? NVfocVRvOjR2Nki2N|I>
BAF3 MXfDfZRwfG:6aXOgRZN{[Xl? NGH0e404OiCq NYnmV3d{TE2VTx?= NIXQUHJKSzVyPUCuPVgh|ryP M2DhflI1PDZ6NkOy
NIH-3T3 MVrLbY5ie2ViQYPzZZk> M4frU|EhcA>? MX3Jcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIF[xNVc1VCCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAxNjF4NTFOwG0> MmLrNlQ5OTlzMU[=
NIH-3T3 NGCzeIlMcW6jc3WgRZN{[Xl? M4TVUVEhcA>? MVnJcohq[mm2aX;uJI9nKGi3bXHuJGVOVDRvZoXz[YQhSUyNIFOxNVU3YSCvdYThcpQh\XiycnXzd4VlKGG|c3Xzd4VlKGG|IIDoc5NxcG9vQVzLJIxmfmWuIIfpeIghUUN3MDDv[kAxNjR5ODFOwG0> MVKyOFgyQTFzNh?=
NIH-3T3 MX;LbY5ie2ViQYPzZZk> Mme3NUBp NHG1OmhKdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJGcyOjB{UjDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iBzLkG0PEDPxE1? NUnNdVhqOjR6MUmxNVY>
NIH-3T3 NIi5VXBMcW6jc3WgRZN{[Xl? M1HSOFEhcA>? NX;3UYlQUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{AyOTVzVHnud{BufXSjboSg[ZhxemW|c3XkJIF{e2W|c3XkJIF{KHCqb4PwbI8uSUyNIHzleoVtKHerdHigTWM2OCCxZjCzMlA{QSEQvF2= MkfxNlQ5OTlzMU[=
KARPAS299 MVjLbY5ie2ViQYPzZZk> MUi5NEBucW5? MYnEUXNQ NYLnSHgyUW6qaXLpeIlwdiCxZjDOVG0u\nW|ZXSgRWxMKHCqb4PwbI9zgWyjdHnvckBmgHC{ZYPz[YQhf2m2aDDJR|UxKG:oIECuNVEh|ryP M3L2UVI1QTByN{Ww
MKN 45 NIL1WlVMcW6jc3WgRZN{[Xl? M17rSVEhcA>? M{fLR2ROW09? MnvNTY5pcWKrdHnvckBw\iClLV3leEBxcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwMEKg{txO MWeyOFkxODd3MB?=
A549 NXjNTWU3S3m2b4TvfIlkKEG|c3H5 MVi0PEBp NVrsclI2TE2VTx?= NInHVJlKSzVyIH;mJFQvODh2IN88US=> NFrxZYozPDlyMEizNC=>
NCI-H1975 NFvyeoFEgXSxdH;4bYMhSXO|YYm= NX\jeoVwPDhiaB?= NIGyXW1FVVOR MVHJR|UxKG:oIEeuOVUyKM7:TR?= Mny2NlQ6ODB6M{C=
NCI-H1993 Mn72R5l1d3SxeHnjJGF{e2G7 MWS0PEBp MnPhSG1UVw>? M1\6SmlEPTBib3[gNE4xPjFizszN M4HMbFI1QTByOEOw
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SF539 NVjIPW01T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3zUbmlEPTB;MkC0MlI1KG6P NF71SGNUSU6JRWK=
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DEL MmHtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlLqTWM2OD1|NkmuPUBvVQ>? MWXTRW5ITVJ?
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Becker MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYjJR|UxRTRwMkO5N{DPxE1? NWXBcoRsW0GQR1XS
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NB14 Mlm3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmnFTWM2OD12LkizOVI1KM7:TR?= M{OySnNCVkeHUh?=
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A498 MmHjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVj2NpAyUUN3ME22MlA5PDd|IN88US=> M4TDOnNCVkeHUh?=
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HC-1 MkHnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX;qfolbUUN3ME2xNE41QDR2IN88US=> MVjTRW5ITVJ?
NB69 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4D0U2lEPTB;MUCuOVA1OyEQvF2= NIjTZ2NUSU6JRWK=
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NCI-H720 NH;ZeGxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXvmWlFyUUN3ME2xNk4yPzB3IN88US=> M36xT3NCVkeHUh?=
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NCI-H1648 MofVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUTJR|UxRTF4LkK1OEDPxE1? MWjTRW5ITVJ?
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PF-382 Mmn4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYPLVGNyUUN3ME2yO{4zOjJ|IN88US=> MoLxV2FPT0WU
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LB831-BLC MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1Pn[mlEPTB;M{SuOVE5PCEQvF2= MYjTRW5ITVJ?
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CPC-N Mlq3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX7o[odQUUN3ME20Nk46QTdzIN88US=> M2X1UnNCVkeHUh?=
ES4 NGDZeY9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWOwb41iUUN3ME20OE41OTV|IN88US=> MoXPV2FPT0WU
Daudi NX\IWlkxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlTOTWM2OD12NT6wPFI4KM7:TR?= MYfTRW5ITVJ?
MOLT-4 NFfqVYNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkDGTWM2OD12NT6wPFU{KM7:TR?= M{\vVHNCVkeHUh?=
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NCI-H2126 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{f2bGlEPTB;NEiuPFQ4PiEQvF2= NETtWG5USU6JRWK=
NCI-SNU-16 Mn\PS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYTJR|UxRTR7LkKxOFMh|ryP MX7TRW5ITVJ?
CESS MoO1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYHJR|UxRTR7LkWwPFgh|ryP NFzRepFUSU6JRWK=
A101D NGmwe2lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH61S3NKSzVyPUS5Mlk4OzZizszN NIDqZW1USU6JRWK=

... 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]
+ 展开

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]
+ 展开
  • 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]
+ 展开
  • 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
稳定性 powder
in solvent
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 (g) = 浓度 (mol/L) x 体积 (L) 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 Conditions Sponsor/Collaborators Start Date Phases
NCT03737994 Not yet recruiting ALK Gene Rearrangement|ALK Positive|Lung Non-Squamous Non-Small Cell Carcinoma|Stage IV Lung Cancer AJCC v8|Stage IVA Lung Cancer AJCC v8|Stage IVB Lung Cancer AJCC v8 National Cancer Institute (NCI) April 1 2019 Phase 2
NCT03737994 Not yet recruiting ALK Gene Rearrangement|ALK Positive|Lung Non-Squamous Non-Small Cell Carcinoma|Stage IV Lung Cancer AJCC v8|Stage IVA Lung Cancer AJCC v8|Stage IVB Lung Cancer AJCC v8 National Cancer Institute (NCI) April 1 2019 Phase 2
NCT03874273 Recruiting Inflammatory Myofibroblastic Tumor Federal Research Institute of Pediatric Hematology Oncology and Immunology February 1 2019 Phase 2|Phase 3
NCT03874273 Recruiting Inflammatory Myofibroblastic Tumor Federal Research Institute of Pediatric Hematology Oncology and Immunology February 1 2019 Phase 2|Phase 3
NCT03672643 Recruiting ALK-positive NSCLC Pfizer January 28 2019 Phase 4
NCT03672643 Recruiting ALK-positive NSCLC Pfizer January 28 2019 Phase 4

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.

Selleck产品目录册

c-Met Signaling Pathway Map

c-Met Inhibitors with Unique Features

  • 选择性强的c-Met抑制剂

    PF-04217903 : C-Met-selective, IC50=4.8 nM.

  • 活性最高的c-Met抑制剂

    INCB28060 : C-Met, IC50=0.13 nM.

  • 用于临床的c-Met抑制剂

    Tivantinib (ARQ 197) : Phase III for Hepatocellular Carcinoma.

  • 最新的c-Met抑制剂

    EMD 1214063 New : Potent and selective c-Met inhibitor with IC50 of 4 nM, >200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer.

相关c-Met产品

  • NPS-1034 New

    NPS-1034是一种双Met/Axl抑制剂，IC50分别为48 nM和10.3 nM。

  • Erlotinib New

    Erlotinib 是一种EGFR抑制剂，IC50 为 2 nM，对EGFR的敏感性比对人c-Src 或 v-Ab高1000多倍。

  • R428 (BGB324|Bemcentinib) New

    R428 (BGB324)是一种Axl抑制剂，IC50为14 nM，作用于Axl比作用于Abl选择性高100倍以上。作用于Axl选择性也比作用于Mer和Tyro3(高50到100倍)及InsR， EGFR， HER2，和PDGFRβ(高100倍以上)高。

  • Foretinib (GSK1363089)

    Foretinib (GSK1363089)是一种ATP竞争性的HGFR和VEGFR抑制剂，对Met和KDR作用最强，在无细胞试验中IC50分别为0.4 nM和0.9 nM。对Ron， Flt-1/3/4， Kit， PDGFRα/β和Tie-2作用效果稍弱，对FGFR1和EGFR几乎没有抑制活性。Phase 2。

  • Capmatinib (INCB28060)

    Capmatinib (INCB28060)是一种新型的，ATP竞争性c-MET抑制剂，无细胞试验中IC50为0.13 nM，对RONβ，EGFR和HER-3无活性。Phase 1。

    Features:INCB28060 对c-MET RTK家族的RONβ以及EGFR RTK家族的EGFR和HER-3不具有活性。

  • Tivantinib (ARQ 197)

    Tivantinib (ARQ 197)是第一个非ATP竞争性的c-Met抑制剂，在无细胞试验中Ki为0.355 μM，对Ron几乎没有作用活性，对EGFR， InsR， PDGFRα和FGFR1/4没有抑制作用。Phase 3。

    Features:ARQ-197是第一个应用到晚期人类临床试验的c-Met选择性抑制剂。

  • PHA-665752

    PHA-665752是一种有效的，选择性的，ATP竞争性c-Met抑制剂，在无细胞试验中IC50为9 nM，对c-Met的选择性比对 RTKs和 STKs高50倍以上。

  • BMS-777607

    BMS-777607是一种Met相关的抑制剂，作用于c-Met，Axl，Ron和Tyro3，在无细胞试验中IC50分别为3.9 nM，1.1 nM，1.8 nM和4.3 nM，作用于Met相关靶点比作用于Lck， VEGFR-2，和TrkA/B选择性高40倍，比作用于其他受体和非受体激酶选择性高500多倍。Phase 1/2。

    Features:BMS 777607是有效的Met家族成员抑制剂，比作用于Lck, VEGFR-2,和TrkA/B的选择性高40多倍，比作用同样其他受体和非受体激酶选择性高500多倍。

  • PF-04217903

    PF-04217903是一种选择性的，ATP竞争性c-Met抑制剂，在A549细胞中IC50为4.8 nM，对致癌基因突变型敏感(对Y1230C突变型没有活性)。Phase 1。

  • SU11274

    SU11274是一种选择性Met抑制剂，在无细胞试验中IC50为10 nM，对PGDFRβ，EGFR和Tie2没有作用。

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID