Ponatinib (AP24534)

For research use only. Not for use in humans.

目录号:S1490 中文名称:帕纳替尼

Ponatinib (AP24534) Chemical Structure

CAS No. 943319-70-8

Ponatinib (AP24534)是一种新型有效的多靶点抑制剂,在无细胞试验中作用于Abl,PDGFRα,VEGFR2,FGFR1和Src,IC50分别为0.37 nM,1.1 nM,1.5 nM,2.2 nM和5.4 nM。Ponatinib (AP24534)可抑制自噬。

规格 价格 库存 购买数量  
10mM (1mL in DMSO) RMB 819.31 现货
RMB 903.01 现货
RMB 3034.48 现货
RMB 7959.08 现货
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客户使用Selleck生产的Ponatinib (AP24534)发表文献138篇:

产品安全说明书

Bcr-Abl抑制剂选择性比较

生物活性

产品描述 Ponatinib (AP24534)是一种新型有效的多靶点抑制剂,在无细胞试验中作用于Abl,PDGFRα,VEGFR2,FGFR1和Src,IC50分别为0.37 nM,1.1 nM,1.5 nM,2.2 nM和5.4 nM。Ponatinib (AP24534)可抑制自噬。
靶点
Abl [1]
(Cell-free assay)
PDGFRα [1]
(Cell-free assay)
VEGFR2 [1]
(Cell-free assay)
FGFR1 [1]
(Cell-free assay)
c-Src [1]
(Cell-free assay)
0.37 nM 1.1 nM 1.5 nM 2.2 nM 5.4 nM
体外研究

Ponatinib是有效的可用于口服的多靶点激酶抑制剂,作用于野生型细胞,及T315I 突变细胞IC50分别为1.2和8.8nM。[1] Ponatinib抑制Ba/F3衍生细胞系的增殖。[2] Ponatinib作用于表达野生型或T315I突变型BCR-ABL的CML细胞系,有效抑制BCR-ABL调节的信号。Ponatinib阻断在细胞瘤筛选时产生抗性突变。[3] Ponatinib也抑制VEGFR和FGFR家族激酶,在体外抑制FLT3, KIT, FGFR1,和PDGFRa激酶活性时IC50分别为13, 13, 2, 和1 nM.[4]Ponatinib抑制全部4种RTKs磷酸化,存在剂量依赖性,IC50值为0.3到20 nM。然而,Ponatinib抑制表达野生型FLT3的RS4;11细胞时IC50>100 nM。

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
EoL-1-cell NVXqXmVQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXrlToJlUUN3ME2wMlAxODByMECzOVkh|ryP MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVcyQDN5Lze+V2FPT0WUPD;hQi=>
MV-4-11 NEjuVJNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXHDRlJkUUN3ME2wMlAxODB7NU[g{txO NYTrbXp5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5MUizO{8oRlODTlfFVlww[T5?
MEG-01 M2nD[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFraUFJKSzVyPUCuNFAxOTJ6IN88US=> MmrwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OTh|Nz:nQnNCVkeHUkyvZV4>
LAMA-84 M2PnXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3f2RWlEPTB;MD6wNFAyPjVizszN NYHTOGg4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5MUizO{8oRlODTlfFVlww[T5?
CGTH-W-1 NHjZclRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2D5b2lEPTB;MD6wNFE3QSEQvF2= NEPZcJo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTdzOEO3M{c,W0GQR1XSQE9iRg>?
KASUMI-1 M3WyVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXTDSJVKUUN3ME2wMlAxOjF5IN88US=> MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVcyQDN5Lze+V2FPT0WUPD;hQi=>
BE-13 NH3HZnFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFr2eYlKSzVyPUCuNFAzPTlizszN NHjoN|A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTdzOEO3M{c,W0GQR1XSQE9iRg>?
CTV-1 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWq5RoE6UUN3ME2wMlAxPTJzIN88US=> MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVcyQDN5Lze+V2FPT0WUPD;hQi=>
NKM-1 NWDx[mVNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWXUXXlZUUN3ME2wMlAxPjV3IN88US=> MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVcyQDN5Lze+V2FPT0WUPD;hQi=>
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GDM-1 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWS0VFR5UUN3ME2wMlAyQDN|IN88US=> NYHlNHd1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5MUizO{8oRlODTlfFVlww[T5?
AN3-CA NF7wOYVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX[xeGh3UUN3ME2wMlAyQDd|IN88US=> NWXUTndsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5MUizO{8oRlODTlfFVlww[T5?
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Daudi M3yyPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkftTWM2OD1yLkCyOVM4KM7:TR?= NVz3R|NsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5MUizO{8oRlODTlfFVlww[T5?
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DOHH-2 NYrxO251T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NInLN4xKSzVyPUCuNFQ5ODNizszN MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVcyQDN5Lze+V2FPT0WUPD;hQi=>
HuO9 NFPseHFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkLXTWM2OD1yLkC1OFQ5KM7:TR?= NXO2SFdnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5MUizO{8oRlODTlfFVlww[T5?
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NCI-H1623 NFL3V2JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkTBTWM2OD12Mz60OlQh|ryP MkfNQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OTh|Nz:nQnNCVkeHUkyvZV4>
KNS-81-FD NWXDPHFIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlvSTWM2OD12Mz63OlIh|ryP MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVcyQDN5Lze+V2FPT0WUPD;hQi=>
TGBC1TKB MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX3JR|UxRTR|LkmwPVkh|ryP MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVcyQDN5Lze+V2FPT0WUPD;hQi=>
RERF-LC-MS Mm\YS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2HLd2lEPTB;NEOuPVI5OSEQvF2= NH;BTHY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTdzOEO3M{c,W0GQR1XSQE9iRg>?
PC-3 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlPITWM2OD12ND60N|Q4KM7:TR?= MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVcyQDN5Lze+V2FPT0WUPD;hQi=>
HuP-T4 NFXaUYhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXrJR|UxRTR2LkS0O|Qh|ryP NUHR[GVmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5MUizO{8oRlODTlfFVlww[T5?
NCI-H510A MoPXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mnn0TWM2OD12ND63NFgh|ryP NYDjb2tIRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5MUizO{8oRlODTlfFVlww[T5?
LB2518-MEL MkO4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MljZTWM2OD12ND63PVM4KM7:TR?= NGrQW2g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTdzOEO3M{c,W0GQR1XSQE9iRg>?
TE-5 M3PsRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2TXfmlEPTB;NEWuPVU5OSEQvF2= MkjDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OTh|Nz:nQnNCVkeHUkyvZV4>
EW-24 MmnYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2LqOmlEPTB;NE[uNVczOyEQvF2= MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVcyQDN5Lze+V2FPT0WUPD;hQi=>
LB647-SCLC MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHjTcmVKSzVyPUS2MlIyPTVizszN M2K0UlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzF6M{evK|5USU6JRWK8M4E,
NCI-H524 MkDyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVHTdIFNUUN3ME20Ok44OTh3IN88US=> NIrGOIk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTdzOEO3M{c,W0GQR1XSQE9iRg>?
EW-11 NHzyZlBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVH2eItnUUN3ME20Ok46Ozd|IN88US=> M2nielxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzF6M{evK|5USU6JRWK8M4E,
KALS-1 NYWxUIxOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3nLeGlEPTB;NEeuNlA3PiEQvF2= MoPiQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OTh|Nz:nQnNCVkeHUkyvZV4>
BT-474 M1ezPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnnyTWM2OD12Nz60NlE3KM7:TR?= M2XhcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzF6M{evK|5USU6JRWK8M4E,
SK-N-AS MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkXPTWM2OD12Nz64PFgh|ryP M2OyV|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzF6M{evK|5USU6JRWK8M4E,
HCC2157 M4K2Vmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVPvSGY2UUN3ME20PE4xPzZizszN MkT5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OTh|Nz:nQnNCVkeHUkyvZV4>
HCC1954 NFX5VnZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlzBTWM2OD12OD6xO|A1KM7:TR?= MnTxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OTh|Nz:nQnNCVkeHUkyvZV4>
FADU NWLhWIJJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWnrVIlWUUN3ME20PE4{ODNzIN88US=> MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVcyQDN5Lze+V2FPT0WUPD;hQi=>
S-117 Ml:wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF3hNWtKSzVyPUS4MlM5OTVizszN MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVcyQDN5Lze+V2FPT0WUPD;hQi=>
LS-1034 MoDrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1W0c2lEPTB;NEiuO|A3PyEQvF2= M2rNSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzF6M{evK|5USU6JRWK8M4E,
CAMA-1 NGP5bIpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MorDTWM2OD12OT61OVQ{KM7:TR?= NGq1cYY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTdzOEO3M{c,W0GQR1XSQE9iRg>?
LU-134-A NGXRNVFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mnr2TWM2OD12OT64NFg2KM7:TR?= NX;YXHpJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5MUizO{8oRlODTlfFVlww[T5?
NCI-H1838 M4rE[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mli4TWM2OD12OT64NFg4KM7:TR?= NGn4cJk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTdzOEO3M{c,W0GQR1XSQE9iRg>?

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
pSrc / Src / pPlcg / Plcg / pStat5 / Stat5 ; 

PubMed: 22781593     


In (B) inhibition of Src, Plcg and Stat5 was seen in MLNAF cell lines treated with Ponatinib; ZNF112 expresses ZMYM2–FGFR1, CEP2A and CEP5A cells express CEP110–FGFR1 and BBC2 expresses BCR–FGFR1.

pFGFR1(pY20) / FGFR1; 

PubMed: 22781593     


Western blot analysis, using various antibodies specific for downstream targets of FGFR1, demonstrates that Ponatinib inhibits the activation of Plcg and Src as a result of inhibiting the FGFR1 fusion kinase in human KG1 cells. 

cleaved caspase-3 / cleaved caspase-7 / BAX / Bcl-2; 

PubMed: 30959969     


Western blot analysis of cleaved caspase-3, cleaved caspase-7, Bax, Bcl-2, and β-Tubulin (control) in treated cells.

p-Rb(S807/811) / Rb / CDK4 / CDK6 / Cyclin D1 / CDK2 / Cyclin E1; 

PubMed: 30959969     


Western blot analysis of Rb/p-Rb, CDK4, CDK6, Cyclin D1, CDK2, Cyclin E1, and β-Tubulin (control) in the SK-Hep-1 and SNU-423 cells treated with ponatinib. 

RAD51; 

PubMed: 30959969     


The effect of ponatinib on the concentration of Rad51 in SK-Hep-1 and SNU-423 cells.

p-MEK / MEK / p-ERK / ERK; 

PubMed: 30959969     


Effect of ponatinib on the phosphorylation of Mek and Erk. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a control.

c-Jun / p-JNK(T183/Y185) / JNK; 

PubMed: 30959969     


Effect of ponatinib on the phosphorylation of JNK and c-Jun. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a control.

p-p38 MAPK / p38 MAPK; 

PubMed: 30959969     


Effect of ponatinib on the phosphorylation of p38. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a control.

p-JAK2 / JAK2 / p-STAT3 / STAT3; 

PubMed: 30959969     


Effect of ponatinib on the phosphorylation of Jak2, and Stat3. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as a control.

PI3K p85 / p-PI3K / p-PDK1 / PDK1 / p-mTOR / mTOR; 

PubMed: 30959969     


Effects of ponatinib on the protein concentration and phosphorylation of PI 3-kinase, PDK1, Akt, and mTOR in HCC cells. 

p-PDGFRα / PDGFRα; 

PubMed: 24472312     


Ponatinib inhibited phosphorylation of PDGFRα in a concentration-dependent manner. EOL-1 and BaF3-WT or -T674I FIP1L1-PDGFRα cells were exposed to escalating concentrations of ponatinib for 24 h.

PARP / Caspase-3 / Active Caspase-3; 

PubMed: 24472312     


The concentration- (for 24 h) and time-dependent (1 nM for EOL-1, 300 nM for BaF3-WT and -T674I FIP1L1-PDGFRα cells) cleavage of PARP and caspase-3 triggered by ponatinib was analyzed by immunoblotting.

AIF / Cyto C ; 

PubMed: 24472312     


Ponatinib elicited release of AIF and cytochrome c into the cytosol. Cells were treated with 1 nM ponatinib for the indicated durations and the cytosolic fraction was extracted with digitonin buffer. Levels of AIF and Cytochrome c (Cyto c) were detected by immunoblotting.

Mcl-1 / Survivin / Bcl-Xl / XIAP / Bax / Bcl-2 / Bim; 

PubMed: 24472312     


Immunoblotting of apoptosis-related proteins in CEL cells after treatment for 24 h.

β-catenin ; 

PubMed: 24472312     


Ponatinib concentration-dependently lowered β-catenin. EOL-1 cells were incubated with ponatinib for 24 h, and cytoplasmic and nuclear extracts were determined by immunoblotting.

β-catenin; 

PubMed: 24472312     


Analysis of β-catenin localization. EOL-1 cells were pretreated with 1 nM ponatinib for 24 h, immunofluorescence analysis was performed with anti-β-catenin. Nuclei were stained with 4,6-diamidino-2-phenylindole (DAPI). 

ABL; 

PubMed: 19878872     


In vitro [γ-32P]-ATP autophosphorylation of full-length (A) ABL or (B) ABLT315I kinase treated with AP24534, imatinib, nilotinib, or dasatinib. After incubation of tyrosine-dephosphorylated enzyme with the indicated inhibitor in the presence of [γ-32P]-ATP and separation by SDS-PAGE, signal intensity was measured by autoradiography.

22781593 30959969 24472312 19878872
Growth inhibition assay
Cell viability; 

PubMed: 30174789     


(A) Effect of Ponatinib on basal viability of HUVECs. The cells were treated with Ponatinib at indicated concentrations or 0.1% DMSO (vehicle control) for 24 h.

30174789
体内研究 Ponatinib抑制取自FLT3-ITD阳性AML病人的原代白血病细胞,而不抑制表达阴性FLT3的AML病人的白血病细胞。[3]

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

激酶实验:

通过同质时间分辨荧光共振能量转移法(TR-FRET),使用纯化的人类野生型ABL激酶,T315I突变型ABL激酶,及生物素化的磷酸激酶底物肽: 生物素-EKKMAAEAIYAAPFAK-NH2,测定野生型ABL和T315I突变型ABL活性的抑制激酶反应在全LANCE激酶buffer (LKB)中进行,LKB包括20 mM NaHEPES(pH 为7.4), 0.1 mg ⁄ mL BSA, 1 mM ATP, 10 mM MgCl2, 及0.41 mM DTT,在提前用1% BSA(溶于PBS)包被的96孔板上4oC下过夜。用于激酶反应,Ponatinib稀释物和野生型ABL, T315I突变型ABL (40 pM), 及底物肽(50 nM), 在室温下温育1小时(T315I突变型ABL)或2小时(野生型ABL)。加入15 nM 抑制剂, 6 nM 铕标记的磷酸酪氨酸抗体(磷酸化位点在第66为酪氨酸上),及60 nM 别藻蓝素标记的链酶亲和素,终止反应。实验板在室温下黑暗温育20分钟,使用Wallac Victor2V读数器读取615和665nm处的荧光值。在孔中数据平均值中插入抑制剂的3倍连续稀释液,再读取665nm处荧光值,计算IC50值。
细胞实验:[1]
- 合并
  • Cell lines: Ba ⁄ F3细胞
  • Concentrations: 0-625 nM, 和0-10 µM
  • Incubation Time: 72小时
  • Method: Ba/F3细胞系按每孔4×103个细胞分布在96孔板上(4×103),和梯度浓度Ponatinib温育72小时。Ponatinib浓度范围为: 0-625 nM 作用于表达BCR-ABL细胞,0-10 µM 用于测定BCR-ABL阴性细胞。使用MTS实验测定细胞增殖,取三次平行实验平均值测定IC50值。
    (Only for Reference)
动物实验:[3]
- 合并
  • Animal Models: 皮下植入MV4-11细胞移植瘤(1×107,50%基质胶中) 的雌性CB.17 SCID鼠
  • Dosages: 每天处理一次,持续4周
  • Administration: 口服饲喂处理
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 30 mg/mL (56.33 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):
1% CMC Na
30mg/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 532.56
化学式

C29H27F3N6O

CAS号 943319-70-8
储存条件 粉状
溶于溶剂
别名 N/A

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系Selleck为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % ddH2O
计算重置

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
NCT04554459 Not yet recruiting Drug: Ponatinib 15 MG Oral Tablet Acute Lymphoblastic Leukemia Adult|Ph+ ALL|Newly Diagnosed Institute of Hematology and Blood Transfusion Czech Republic|CZECRIN - Czech Clinical Research Infrastructure Network October 30 2020 Phase 2
NCT04160546 Recruiting Drug: Ponatinib 15 MG|Drug: Acetylsalicylic acid 100 MG Chronic Myeloid Leukemia Chronic Phase Fundacion CRIS de Investigación para Vencer el Cáncer|Incyte Biosciences UK|Apices Soluciones S.L. January 17 2020 Phase 2
NCT03934372 Recruiting Drug: Ponatinib Acute Myeloid Leukemia|Accelerated Phase Chronic Myeloid Leukemia|Blast Phase Chronic Myeloid Leukemia|Chronic Phase Chronic Myeloid Leukemia|Acute Lymphoblastic Leukemia|Acute Lymphocytic Leukemia|Leukemia|Lymphoma|Solid Tumors Incyte Biosciences International Sàrl|Incyte Corporation January 29 2020 Phase 1|Phase 2
NCT04070443 Recruiting Drug: Ponatinib|Drug: Imatinib Philadelphia Chromosome Positive CML|BCR-ABL Positive Chronic Myelogenous Leukemia Centre Leon Berard November 13 2019 Phase 2
NCT03895671 Recruiting Drug: Ponatinib|Drug: Azacitidine CHRONIC MYELOGENOUS LEUKAEMIA IN ACCELERATED PHASE|CHRONIC MYELOGENOUS LEUKAEMIA IN MYELOID BLAST CRISIS Versailles Hospital June 19 2019 Phase 2

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常见问题及建议解决方法

  • 问题 1:

    Is the pre-solubilized inhibitor suitable for in vivo whole animal studies? Whether the solvent contains any non-DMSO stabilizer?

  • 回答:

    Our 10mM Ponatinib in DMSO solution is in pure DMSO and there is not other stabilizer added. You can use it for animal study. The vehicle we suggest for Ponatinib is: 30% PEG400/0.5% Tween80/5% Propylene glycol. It is a milky suspension used for oral gavage.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID