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 NXnmOGpHS3m2b4TvfIlkKEG|c3H5 M1T0NVQ5KGh? NWXhOXA2TE2VTx?= M1;URWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KG2xdYPlJGJCTjNiY3XscJMh\XiycnXzd4lv\yCDTFugSlEyPzSOIH31eIFvfCClb3X4dJJme3OrbnegSW1NPCC5aYToJGlEPTBib3[gNE43OiEQvF2= NGXUbXozOTV5MkW4PS=>
BAF3 NI\qdG1EgXSxdH;4bYMhSXO|YYm= MWO0PEBp MkKxSG1UVw>? NEi3PYpEgXSxdH;4bYNqfHliYXfhbY5{fCCvb4Xz[UBDSUZ|IHPlcIx{KGW6cILld5NqdmdiQVzLJGwyOTl4TTDteZRidnRiY3;lfJBz\XO|aX7nJGVOVDRid3n0bEBKSzVyIH;mJFIvOiEQvF2= NEXjTnAzOTV5MkW4PS=>
BAF3 NIjKTWJEgXSxdH;4bYMhSXO|YYm= M{jydVQ5KGh? MmjqSG1UVw>? MYDDfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRWY{KGOnbHzzJIV5eHKnc4PpcochTU2OND3BUGshf2m2aDDJR|UxKG:oIECuNlgh|ryP NXTRcIZ1OjF3N{K1PFk>
Kelly NH[3OXhEgXSxdH;4bYMhSXO|YYm= MW\EUXNQ NIj6emVEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBM\WyueTDj[YxteyCneIDy[ZN{cW6pIFHMT{BHOTF5NFygcZV1[W62IIfpeIghUUN3MDDv[kAxNjR{IN88US=> NF\6bGwzOTV5MkW4PS=>
SH-SY5Y NXztbHFyS3m2b4TvfIlkKEG|c3H5 NXv2d4FkTE2VTx?= MVvDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDTTE1UYTW\IHPlcIx{KGW6cILld5NqdmdiQVzLJGYyOTd2TDDteZRidnRid3n0bEBKSzVyIH;mJFAvPTNizszN M3;1PVIyPTd{NUi5
SMS-KCN MYnDfZRwfG:6aXOgRZN{[Xl? MkPRSG1UVw>? MYHDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDTUXMuU0OQIHPlcIx{KGW6cILld5NqdmdiQVzLJHIyOjd3UTDteZRidnRid3n0bEBKSzVyIH;mJFAvQTFizszN MWqyNVU4OjV6OR?=
BAF3 MnLqR5l1d3SxeHnjJGF{e2G7 NWnxcY5vPDhiaB?= MnXxSG1UVw>? NIi4TlREgXSxdH;4bYNqfHliYXfhbY5{fCCvb4Xz[UBDSUZ|IHPlcIx{KGW6cILld5NqdmdiVHXsMWFNUyC5aYToJGlEPTBib3[gNE4yQSEQvF2= MoP4NlE2PzJ3OEm=
3T3 Mm\FSpVv[3Srb36gRZN{[Xl? M1LseFEhcA>? NXPZfmVXTE2VTx?= NFXaN2xKdmirYnn0bY9vKG:oIGLPUkBie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6wPEDPxE1? M4TGPVIyQDF{NEG0
3T3-E M4KwZmZ2dmO2aX;uJGF{e2G7 M1jRUVEhcA>? NXvwO|B{TE2VTx?= NHjZdmdKdmirYnn0bY9vKG:oIGTJSVIh[XO|ZYPz[YQh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwNES4JO69VQ>? M1jKNVIyQDF{NEG0
A549 MmXmT4lv[XOnIFHzd4F6 NUXZ[mt6OSCq NYnyc|V1TE2VTx?= M4fWOWlvcGmkaYTpc44hd2ZiaIXtZY4hemWlb33ibY5idnRiYz3NSXQhc2mwYYPlJIV5eHKnc4Pl[EBie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGhITi2rbnT1Z4VlKGG3dH;wbI9{eGixconsZZRqd25id3n0bEBKSzVyIH;mJFAvODB6IN88US=> NEHC[GIzOThzMkSxOC=>
BAF3-BCL NUPDTZFUTnWwY4Tpc44hSXO|YYm= NFnMNowyKGh? NU\MXY9UTE2VTx?= MnTYTY5pcWKrdHnvckBw\iCDQlygZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDFwMUW5JO69VQ>? NYq4[HlLOjF6MUK0NVQ>
HEK293 MkjFSpVv[3Srb36gRZN{[Xl? NWPoZ2M5OSCq NEPu[olFVVOR M1[wfmlvcGmkaYTpc44hd2ZiQWjMJIF{e2W|c3XkJIF{KGe{b4f0bEBn[WO2b4KtbY5lfWOnZDDheZRweGixc4Doc5J6dGG2aX;uJJdqfGhiSVO1NEBw\iByLkK5OEDPxE1? NELROY4zOThzMkSxOC=>
HEK293 NXHLXG5ZTnWwY4Tpc44hSXO|YYm= M{jTe|EhcA>? NXyzO3Q2TE2VTx?= NWm0c41EUW6qaXLpeIlwdiCxZjDJVkBie3Onc4Pl[EBieyCpcn;3eIgh\mGldH;yMYlv\HWlZXSgZZV1d3Cqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMj64PFch|ryP M4XQN|IyQDF{NEG0
Jurkat MlLoSpVv[3Srb36gRZN{[Xl? NGfSfXQyKGh? Ml;xSG1UVw>? NWriOoJYUW6qaXLpeIlwdiCxZjDMR2sh[XO|ZYPz[YQh[XNiZ4Lve5RpKG[jY4Tvdk1qdmS3Y3XkJIF2fG:yaH;zdIhwenmuYYTpc44hf2m2aDDJR|UxKG:oIEKuO|QyKM7:TR?= MUOyNVgyOjRzNB?=
KARPAS299 MVPLbY5ie2ViQYPzZZk> M3v6UlEhcA>? NF3ITnhFVVOR Mo[4TY5pcWKrdHnvckBw\iCDTFugZZN{\XO|ZXSgZZMh\3Kxd4ToJIZi[3Sxcj3pcoR2[2WmIHH1eI9xcG:|cHjvdplt[XSrb36ge4l1cCCLQ{WwJI9nKDBwMEKg{txO M4\ibVIyQDF{NEG0
PAE NHmwVIJHfW6ldHnvckBCe3OjeR?= M{Lme|EhcA>? MkX1SG1UVw>? NWjGcIxkUW6qaXLpeIlwdiCxZjDUVmtDKGG|c3Xzd4VlKGG|IHfyc5d1cCCoYXP0c5IucW6mdXPl[EBifXSxcHjvd5Bpd3K7bHH0bY9vKHerdHigTWM2OCCxZjCwMlM6QSEQvF2= M{j5WVIyQDF{NEG0
BAF3 M4nwWWZ2dmO2aX;uJGF{e2G7 NIPXXIwzNTNiZB?= MV\EUXNQ MWDJcohq[mm2aX;uJI9nKFSHTD3meZNm\CCrboP1cIlvKHKnY3XweI9zKGW6cILld5Nm\CC5aYToJGlEPTBib3[gNU43PDNizszN NInjfGkzOzd2MkK1Ni=>
KARPAS299 NXTsVlNMS3m2b4TvfIlkKEG|c3H5 MXyyMVMh\A>? MUjEUXNQ MXHJR|UxRTBwME[0NkDPxE1? MkHnNlM4PDJ{NUK=
EBC1 NF;RVpNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mli0O|IhcA>? MX\EUXNQ Mn;NTWM2OD1yLkCyN{DPxE1? MWWyN|k6OzN{OB?=
HCT116 NIDxcnhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NILNeGE4OiCq NHTMc5RFVVOR M2X2XGlEPTB;MUSuPFIh|ryP MU[yN|k6OzN{OB?=
MCF7 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIPYVFQ4OiCq NYHYUHA5TE2VTx?= MnPaTWM2OD17LkW4JO69VQ>? NEnxblczOzl7M{OyPC=>
MDA-MB-231 NYPrSodtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2fkd|czKGh? MnHQSG1UVw>? MnOwTWM2OD1zMD64JO69VQ>? NH6wO2szOzl7M{OyPC=>
MKN45 M1mwXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHjlUYg4OiCq Mo\XSG1UVw>? M1;v[WlEPTB;MD6wNVMh|ryP MoXVNlM6QTN|Mki=
NCI-H441 MkXsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml3TO|IhcA>? NVrlSmJzTE2VTx?= NI\mT|VKSzVyPUG3MlI2KM7:TR?= MoWwNlM6QTN|Mki=
NCI-H661 M4f5cWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1zRVFczKGh? M1;h[mROW09? MnjlTWM2OD1zMT60O{DPxE1? NGrFbWQzOzl7M{OyPC=>
SK-MEL-28 M4PyTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUnzN|NVPzJiaB?= MnjBSG1UVw>? M4TQeWlEPTB;MUCuPVch|ryP NIPqZ5IzOzl7M{OyPC=>
SKOV3 NWnNRYVJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWXiS5M{PzJiaB?= NETCe3VFVVOR NHrBO2RKSzVyPUGyMlg2KM7:TR?= NY\Pe2d7OjN7OUOzNlg>
SNU5 NVLKXXhsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{DsT|czKGh? Mn\hSG1UVw>? MWXJR|UxRTBwMEG2JO69VQ>? MlSwNlM6QTN|Mki=
NCI-H2228 M1PCcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWC3NkBp MU\EUXNQ NX7tUoFwUW6qaXLpeIlwdiCxZjDBUGsu\nW|aX;uJIRzcX[nbjDj[YxtKHC{b3zp[oVz[XSrb36ge4l1cCCLQ{WwJI9nKDBwMUG4JO69VQ>? NXrY[Hh[OjR2M{K5NFk>
NCI-H3122 MlW4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Moe1O|IhcA>? MYTEUXNQ NIK1WIJKdmirYnn0bY9vKG:oIFHMT{1nfXOrb36g[JJqfmWwIHPlcIwheHKxbHnm[ZJifGmxbjD3bZRpKEmFNUCgc4YhOC5zMEig{txO M3TTRlI1PDN{OUC5
NCI-H3122 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUXJ[oliPzJiaB?= NILtUYxFVVOR MlO0TY5pcWKrdHnvckBw\iCDTFut[pV{cW:wIHTybZZmdiClZXzsJJBzd2yrZnXyZZRqd25iaX6gbJVu[W5iTlPJMWg{OTJ{IHPlcIx{KGijcnLvdolv\yCDTFugS|EzPjmDIH31eIFvfCC5aYToJGlEPTBib3[gNE43OjNizszN NIizU4EzPDR|MkmwPS=>
NCI-H3122 MmrHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGe4Wnc4OiCq M4LnTWROW09? NGTxTnBKdmirYnn0bY9vKG:oIFHMT{1nfXOrb36g[JJqfmWwIHPlcIwheHKxbHnm[ZJifGmxbjDpckBpfW2jbjDOR2kuUDNzMkKgZ4VtdHNiaHHyZo9zcW6pIFHMT{BNOTF7Nl2gcZV1[W62IIfpeIghUUN3MDDv[kAxNjh|ODFOwG0> MmjjNlQ1OzJ7MEm=
NIH-3T3 NVLx[ZdrU2mwYYPlJGF{e2G7 NUW3VHRvOSCq MXXEUXNQ NFHLcIJKdmirYnn0bY9vKG:oIHj1cYFvKHerbHSgeJlx\SCHTVy0MYZ2e2WmIFHMT{BmgHC{ZYPz[YQh[XO|ZYPz[YQh[XNicHjvd5Bpd3K7bHH0[YQhSUyNIHzleoVtKHerdHigTWM2OCCxZjCwMlA5KM7:TR?= MmHSNlQ1OzJ7MEm=
NIH-3T3 MXLLbY5ie2ViQYPzZZk> MWOxJIg> MkLZSG1UVw>? NIDiVHRKdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJGcyOjZ7QTDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLk[wOUDPxE1? NFnK[XAzPDR|MkmwPS=>
NIH-3T3 NH\kRlBMcW6jc3WgRZN{[Xl? NHfie|YyKGh? M13PO2ROW09? NH\1NHhKdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJHMyOjB4WTDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iByLk[yOkDPxE1? NIDuUXYzPDR|MkmwPS=>
NIH-3T3 NVXsVpJlU2mwYYPlJGF{e2G7 NHnCOG0yKGh? NH;iUXBFVVOR M{TXemlvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugUFEyQT[PIH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDBwOESzJO69VQ>? NWiybWVLOjR2M{K5NFk>
NIH-3T3 MYrLbY5ie2ViQYPzZZk> NF:xO4cyKGh? NVT2OWtYTE2VTx?= M{nlbmlvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugUFEyPTKUIH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDFwMEK2JO69VQ>? MnzMNlQ1OzJ7MEm=
BAF3 MmrSSpVv[3Srb36gRZN{[Xl? MV63NkBp M4DJe2ROW09? M2ewbGlvcGmkaYTpc44hd2ZiTmDNM2FNUyC2cnHud4Zm[3SnZDDhd5Nme3OnZDDhd{Bk\WyuIHfyc5d1cCCrbnjpZol1cW:wIIfpeIghUUN3MDDv[kAxNjB3MTFOwG0> NWiwPXpnOjR2Nki2N|I>
BAF3 M4jOfGN6fG:2b4jpZ{BCe3OjeR?= M2mwXVczKGh? MkX4SG1UVw>? NH3IVZJKSzVyPUCuPVgh|ryP MkDiNlQ1Pjh4M{K=
NIH-3T3 M2rIVWtqdmG|ZTDBd5NigQ>? NVzN[5Q5OSCq M1zLTGlvcGmkaYTpc44hd2ZiaIXtZY4hTU2OND3meZNm\CCDTFugSlEyPzSOIH31eIFvfCCneIDy[ZN{\WRiYYPz[ZN{\WRiYYOgdIhwe3Cqbz3BUGshdGW4ZXyge4l1cCCLQ{WwJI9nKDBwMU[1JO69VQ>? M4CxNlI1QDF7MUG2
NIH-3T3 NEDDUlhMcW6jc3WgRZN{[Xl? NHjOSnAyKGh? NWTVS4NRUW6qaXLpeIlwdiCxZjDoeY1idiCHTVy0MYZ2e2WmIFHMT{BEOTF3NmmgcZV1[W62IHX4dJJme3OnZDDhd5Nme3OnZDDhd{BxcG:|cHjvMWFNUyCuZY\lcEB4cXSqIFnDOVAhd2ZiMD60O|gh|ryP MmDoNlQ5OTlzMU[=
NIH-3T3 MX;LbY5ie2ViQYPzZZk> NEPYT5MyKGh? NHOxWJhKdmirYnn0bY9vKG:oIHj1cYFvKEWPTESt[pV{\WRiQVzLJGcyOjB{UjDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iBzLkG0PEDPxE1? MV[yOFgyQTFzNh?=
NIH-3T3 M2P3[WtqdmG|ZTDBd5NigQ>? M3PZWFEhcA>? Ml74TY5pcWKrdHnvckBw\iCqdX3hckBGVUx2LX\1d4VlKEGOSzCxNVUyXGmwczDteZRidnRiZYjwdoV{e2WmIHHzd4V{e2WmIHHzJJBpd3OyaH:tRWxMKGyndnXsJJdqfGhiSVO1NEBw\iB|LkCzPUDPxE1? Mn[1NlQ5OTlzMU[=
KARPAS299 NWPHWGpCU2mwYYPlJGF{e2G7 MortPVAhdWmw NWDMNmxITE2VTx?= Mm\kTY5pcWKrdHnvckBw\iCQUF2t[pV{\WRiQVzLJJBpd3OyaH;yfYxifGmxbjDlfJBz\XO|ZXSge4l1cCCLQ{WwJI9nKDBwMUGg{txO NFLiU4szPDlyMEe1NC=>
MKN 45 M{PlR2tqdmG|ZTDBd5NigQ>? MmTJNUBp MorMSG1UVw>? NIDHR|RKdmirYnn0bY9vKG:oIHOtUYV1KHCqb4PwbI9zgWyjdHnvckB4cXSqIFnDOVAhd2ZiMD6wNkDPxE1? NGTqV24zPDlyMEe1NC=>
A549 NIPZSppEgXSxdH;4bYMhSXO|YYm= M4DQXlQ5KGh? M2nzWGROW09? NULrWG97UUN3MDDv[kA1NjB6NDFOwG0> NF32cHozPDlyMEizNC=>
NCI-H1975 NV7tOZk2S3m2b4TvfIlkKEG|c3H5 MXS0PEBp NXfmXJAzTE2VTx?= M4DBdmlEPTBib3[gO{42PTFizszN MX6yOFkxODh|MB?=
NCI-H1993 MYTDfZRwfG:6aXOgRZN{[Xl? M1raO|Q5KGh? MXLEUXNQ M3\MNGlEPTBib3[gNE4xPjFizszN NEPrPYczPDlyMEizNC=>
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NCI-SNU-16 NFLqcmlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M13WPGlEPTB;NEmuNlE1OyEQvF2= NHqzS45USU6JRWK=
CESS Ml;tS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmW0TWM2OD12OT61NFg5KM7:TR?= M3PY[XNCVkeHUh?=
A101D MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGTMfYRKSzVyPUS5Mlk4OzZizszN NIr1[5ZUSU6JRWK=

... 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
储存条件 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 (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 Conditions Sponsor/Collaborators Start Date Phases
NCT03439215 Recruiting Carcinoma Non-Small-Cell Lung Fondazione Ricerca Traslazionale|Clinical Research Technology S.r.l. June 13 2017 Phase 2
NCT02946216 Unknown status 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 ALK-positive Advanced NSCLC Pfizer|Merck Sharp & Dohme Corp. October 2015 Phase 1
NCT02419287 Recruiting Anaplastic Large Cell Lymphoma ALK-Positive University of Milano Bicocca April 2015 Phase 2
NCT02499614 Unknown status Carcinoma Non-Small-Cell Lung Fondazione Ricerca Traslazionale December 2014 Phase 2
NCT02510001 Active not recruiting 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.

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c-Met Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID