Tozasertib

目录号:S1048 别名: VX-680, MK-0457 中文名称:陶扎色替

仅限科研使用

Tozasertib (VX-680, MK-0457)是一种pan-Aurora抑制剂,对Aurora A作用最强,无细胞试验中Kiapp为0.6 nM,而对Aurora B/Aurora C的作用较弱,对Aurora A选择性比其他55种激酶高100倍。唯二的例外是 Fms-related tyrosine kinase-3 (FLT-3)BCR-ABL tyrosine kinase,也可被 Tozasertib 抑制,对应的Ki值均为30 nM和30 nM。Tozasertib 可诱导凋亡和自噬。Phase 2。

Tozasertib  Chemical Structure

CAS: 639089-54-6

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 1098.34 现货
RMB 1211.51 现货
RMB 3833.09 现货
大包装 有超大折扣

今日订购,明日送达 全国免运费 分装免费 分装成小规格产品(单支最小为1mg)
如1支10mg产品可分装为10支1mg产品

全国免费电话:400-668-6834   |   Email:info@selleck.cn

客户使用Selleck生产的Tozasertib 发表文献122篇:

产品安全说明书

Aurora Kinase抑制剂选择性比较

相关Aurora Kinase产品

生物活性

产品描述 Tozasertib (VX-680, MK-0457)是一种pan-Aurora抑制剂,对Aurora A作用最强,无细胞试验中Kiapp为0.6 nM,而对Aurora B/Aurora C的作用较弱,对Aurora A选择性比其他55种激酶高100倍。唯二的例外是 Fms-related tyrosine kinase-3 (FLT-3)BCR-ABL tyrosine kinase,也可被 Tozasertib 抑制,对应的Ki值均为30 nM和30 nM。Tozasertib 可诱导凋亡和自噬。Phase 2。
靶点
Aurora A [1]
(Cell-free assay)
Aurora C [1]
(Cell-free assay)
Aurora B [1]
(Cell-free assay)
FLT3 [4]
(Cell-free assay)
Bcr-Abl [4]
(Cell-free assay)
0.6 nM(Ki app) 4.6 nM(Ki app) 18 nM(Ki app) 30 nM(Ki) 30 nM(Ki)
体外研究

虽然VX-680具有多激酶特性,VX-680却诱导相似的细胞毒性,IC50约为300 nM,在G2/M期,核内复制期,及转染ABL或FLT-3激酶的BaF3细胞凋亡时,显示一个Aurora B 类似的抑制表现型。VX-680抑制CAL-62细胞增殖,这种作用存在时间依赖性。用VX-680处理14天,明显降低群体的数量和大小,处理8305C下降达到70%,处理CAL-62, 8505C,和BHT-101下降达到90%。用VX-680处理不同ATC细胞,抑制细胞增殖,IC50为25到150  nM,这种作用存在时间和剂量依赖性。在软琼脂中,VX-680明显削弱不同细胞系形成群落的能力。caspase-3的活性分析显示VX-680诱导不同细胞凋亡。VX-680处理CAL-62 细胞12小时,形成DNA含量≥4N细胞累积物。微速摄影分析显示VX-680处理的CAL-62细胞离开细胞中期。VX-680可以抑制组蛋白H3的磷酸化作用。[2] VX-680作用于携带T315I突变的BCR-Abl的病人样本,具有明显抑制活性。[3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BE-13 NHu3OYhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHjBNJBKSzVyPUCuNFA{OzhizszN MnvEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
RS4-11 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXTDSm5lUUN3ME2wMlAxPDB2IN88US=> Mnq5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
MFH-ino NF\abGVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{f4fGlEPTB;MD6wNFk6KM7:TR?= MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O|I5PzhxJ{7TRW5IWkWUPD;hQi=>
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697 MnvyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWHJR|UxRTBwMEK0O|Eh|ryP NF7hU|Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
NALM-6 M{TIVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlXMTWM2OD1yLkCyOVUzKM7:TR?= NF7KcGU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
ES8 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml3JTWM2OD1yLkC0OlE{KM7:TR?= M{HZZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
HUTU-80 MkPyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV\JR|UxRTBwMEWyPVkh|ryP NX7kUZk1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
MV-4-11 NH;XeWtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWG0XFRlUUN3ME2wMlA4Pzh{IN88US=> MkC4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
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BL-41 NFHMbpBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH\ERlRKSzVyPUCuNVA1PDVizszN NH36O2w9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
A4-Fuk MnHNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV\xVlI1UUN3ME2wMlEyPTZ|IN88US=> MkHZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
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TE-11 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1TvZmlEPTB;MD6xOFk5OiEQvF2= NU\wNmRpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
SK-UT-1 Ml\1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX3JR|UxRTBwMUW5OlUh|ryP MljFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
SIG-M5 Mn;JS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWrWWVBMUUN3ME2wMlE3PzB5IN88US=> MmjDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
OCUB-M NETMbYRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NELZVnRKSzVyPUCuNVY6QDNizszN MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O|I5PzhxJ{7TRW5IWkWUPD;hQi=>
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SW982 M2DKRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mm\0TWM2OD1yLkKxN|gh|ryP Mn7KQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
LB647-SCLC MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkjkTWM2OD1yLkKxOVI{KM7:TR?= NULYO|lXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
PSN1 NFfPPI5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1XYdWlEPTB;MD6yNlAzPiEQvF2= NW\KcI1lRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
BB30-HNC MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3vEe2lEPTB;MD6yNlU6OSEQvF2= M1nWWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
ST486 MnnYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{G0U2lEPTB;MD6yN|A5PyEQvF2= MkLhQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
MOLT-4 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXHxN5RmUUN3ME2wMlI{OzN5IN88US=> NVe0TJB3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
EW-16 Mmi2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4jmOmlEPTB;MD6yN|c3QCEQvF2= MnPzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
KS-1 NWHPbmZTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUntc2R3UUN3ME2wMlI{Pzh3IN88US=> MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O|I5PzhxJ{7TRW5IWkWUPD;hQi=>
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EoL-1-cell NHfhNXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVPJR|UxRTBwM{O0OVkh|ryP NHXBdos9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
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HCT116 MVTGeY5kfGmxbjDhd5NigQ>? MmHJN{BpenN? NWXGVlBxUW6qaXLpeIlwdiCxZjDBeZJwemFiQTDwbI9{eGixconsZZRqd25iYYSgWIhzOjh6IILld4llfWViaX6gbJVu[W5iSFPUNVE3KGOnbHzzJJVxKHSxIEGgeW0h[W[2ZYKgN{BpenNiYomgW4V{fGW{bjDicI91KGGwYXz5d4l{ MlizQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzBzNEO0NlMoRjNyMUSzOFI{RC:jPh?=
HCT116 MXLGeY5kfGmxbjDhd5NigQ>? MWSzJIhzew>? NGDSUoNKdmirYnn0bY9vKG:oIFH1do9z[SCEIIDoc5NxcG:{eXzheIlwdiCjdDDUbJIzOzJicnXzbYR2\SCrbjDoeY1idiCKQ2SxNVYh[2WubIOgeZAhfG9iMTD1UUBi\nSncjCzJIhzeyCkeTDX[ZN1\XKwIHLsc5QhdWW2aH;k NY\QXYxCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CxOFM1OjNpPkOwNVQ{PDJ|PD;hQi=>
Sf9 MkXySpVv[3Srb36gZZN{[Xl? NYr5XFNjUW6qaXLpeIlwdiCxZjDHV3QufGGpZ3XkJGFWWk:UQTDBJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW|c3XkJIlvKGKjY4Xsc5ZqenW|IHnu[oVkfGWmIGPmPUBk\WyuczD1d4lv\yCPQmCgZZMhe3Wkc4TyZZRmNCCLQ{WwQVAvODJ|zszN MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODJ|NEm4O{c,OzB{M{S5PFc9N2F-
HeLa NIS4enNHfW6ldHnvckBie3OjeR?= M1\4ZVEzKGi{cx?= MXvJcohq[mm2aX;uJI9nKEG3cn;yZUBCKHCqb4PwbI9zgWyjdHnvckBifCCWaIKyPFghemW|aXT1[UBqdiCqdX3hckBJ\UyjIHPlcIx{KGGodHXyJFEzKGi{czDifUBGVEmVQTygTWM2OD1yLkCxN:69VQ>? MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODVyMkGxOUc,OzB3MEKxNVU9N2F-
HeLa NFLKWJNHfW6ldHnvckBie3OjeR?= MWSxNkBpenN? NXS1fWxSUW6qaXLpeIlwdiCxZjDBeZJwemFiQjDwbI9{eGixconsZZRqd25iYYSgWIhzOjN{IILld4llfWViaX6gbJVu[W5iSHXMZUBk\WyuczDh[pRmeiBzMjDodpMh[nliRVzJV2EtKEmFNUC9NE4yPDkQvF2= NGrCbJY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MEWwNlEyPSd-M{C1NFIyOTV:L3G+
A549 NVzl[4hkSW62aYDyc4xq\mW{YYTpeoUh[XO|YYm= M4j4UFQ5KGi{cx?= NHrxfG5CdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFG1OFkh[2WubIOgZYZ1\XJiNEigbJJ{KGK7IF3UWEBie3OjeTygS2k2OD1|NT64{txO MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODVyMkGxOUc,OzB3MEKxNVU9N2F-
LoVo M{G1cGFvfGmycn;sbYZmemG2aY\lJIF{e2G7 MV[0PEBpenN? NFTBNGxCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFzvWo8h[2WubIOgZYZ1\XJiNEigbJJ{KGK7IF3UWEBie3OjeTygS2k2OD12NT6z{txO M4DRclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyNUCyNVE2Lz5|MEWwNlEyPTxxYU6=
HeLa MWrBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>? NXzTNGNuPDhiaILz MWXBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEinTHGgZ4VtdHNiYX\0[ZIhPDhiaILzJIJ6KE2WVDDhd5NigSxiR1m1NF01Pi5{zszN MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODVyMkGxOUc,OzB3MEKxNVU9N2F-
HeLa M3nNUWNmdGxiY4njcIUh[XO|YYm= MnqwOUB2VQ>? NX\GXmtlOTJiaILz Mlv3R4VtdCCleXPs[UBienKnc4SgbY4hcHWvYX6gTIVN[SClZXzsd{Bie3Onc4Pl[EBieyCmZXPy[YF{\SCrbjDjfYNtcW5iQkGgdJJwfGWrbjDlfJBz\XO|aX;uJIF1KDVidV2gZYZ1\XJiMUKgbJJ{KGK7IGfld5Rmem5iYnzveEBidmGueYPpdy=> MlPMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB3MEKxNVUoRjNyNUCyNVE2RC:jPh?=
HeLa NI\NdXpE\WyuIHP5Z4xmKGG|c3H5 MnX0OUB2VQ>? NHXkOG4yOiCqcoO= MmnER4VtdCCleXPs[UBienKnc4SgbY4hcHWvYX6gTIVN[SClZXzsd{Bie3Onc4Pl[EBieyCmZXPy[YF{\SCrbjDj[IMzKHC{b4TlbY4h\XiycnXzd4lwdiCjdDC1JJVOKGGodHXyJFEzKGi{czDifUBY\XO2ZYLuJIJtd3RiYX7hcJl{cXN? MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODVyMkGxOUc,OzB3MEKxNVU9N2F-
HeLa MVHGeY5kfGmxbjDhd5NigQ>? M{TlXlUhfU1? MUOxNkBpenN? NHHHXGZKdmirYnn0bY9vKG:oIFH1do9z[SCDIIDoc5NxcG:{eXzheIlwdiCjdDDUbJIzQDhicnXzbYR2\SCrbjDoeY1idiCKZVzhJINmdGy|IHH0JFUhfU1iYX\0[ZIhOTJiaILzJIJ6KFenc4Tldo4h[myxdDDhcoFtgXOrcx?= M{L6RlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyNUCyNVE2Lz5|MEWwNlEyPTxxYU6=
HeLa NGjTO2RHfW6ldHnvckBie3OjeR?= MnHzOUB2VQ>? NETl[IUyOiCqcoO= NVPDOGhDUW6qaXLpeIlwdiCxZjDBeZJwemFiQjDwbI9{eGixconsZZRqd25iYYSgWIhzOjN{IILld4llfWViaX6gbJVu[W5iSHXMZUBk\WyuczDheEA2KHWPIHHmeIVzKDF{IHjyd{BjgSCZZYP0[ZJvKGKub4SgZY5idHm|aYO= MlfaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB3MEKxNVUoRjNyNUCyNVE2RC:jPh?=
A549 NHjPWYFCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MkjlOFghcHK| NGX3SZJCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFG1OFkh[2WubIOgZYZ1\XJiNEigbJJ{KGK7IF3UWEBie3OjeTygTWM2OD1|NT64{txO MoLuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB5MkixNVIoRjNyN{K4NVEzRC:jPh?=
LoVo MnXyRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? MVe0PEBpenN? M13DfWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTH;Wc{Bk\WyuczDh[pRmeiB2ODDodpMh[nliTWTUJIF{e2G7LDDJR|UxRTR3LkROwG0> NIrzOXg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MEeyPFEyOid-M{C3NlgyOTJ:L3G+
HeLa NEi1bWdCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MlGyOFghcHK| MUnBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEinTHGgZ4VtdHNiYX\0[ZIhPDhiaILzJIJ6KE2WVDDhd5NigSxiSVO1NF01Pi5{zszN Mn3sQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB5MkixNVIoRjNyN{K4NVEzRC:jPh?=
Assay
Methods Test Index PMID
Western blot DLK / p-MKK7 / MKK7 / p-JNK / JNK p-AURKA / AURKA / Survivin YAP p-AKT / p-GSK3β / Cleaved caspase-3 / Cleaved PARP 23431148 28218735 31160567 21600017
Immunofluorescence α-tubulin / Aurora-A 21600017
Growth inhibition assay Cell viability 21600017
体内研究 VX-680作用于人类AML(HL-60)移植瘤模型明显降低肿瘤尺寸。VX-680按75 mg/kg剂量给药实验鼠,每天腹腔注射两次,持续13天,与对照组相比,平均肿瘤体积下降达98%。肿瘤体积比实验之前初始体积小很多。按12.5 mg/kg剂量每天给药两次,肿瘤生长也明显降低,这种作用存在剂量依赖性。VX-680耐受性很好,只有在使用高剂量时可以观察到实验动物体重稍微降低。通过比较cisplatin,按5.4 mg/kg剂量给药,每四天腹腔注射一次,一共进行三次,抑制肿瘤生长只达9%。VX-680作用于胰脏和结肠移植瘤,也引起肿瘤衰退。VX-680静脉注射给药携带HCT116肿瘤的实验鼠,显示很强的抗癌活性。使用高剂量VX-680(每小时2 mg/kg)处理,明显提高效果,比实验钱的初始肿瘤平均尺寸下降56%。[1]

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:

[3]

  • 激酶抑制实验:

    丙酮酸激酶/乳酸脱氢酶催化NADH的氧化,伴随着ATP的消耗,观察340 nm 处吸光值的降低。反应包括100 mM Tris (pH 为 8), 10 mM MgCl2, 2.2 mM ATP, 1 mM磷酸烯醇丙酮酸, 0.6 mg/ml NADH, 75 ml丙酮酸激酶, 105 ml 乳酸脱氢酶,和0.5 mM 基底肽(序列为EAIYAAPFAKKK)。加入足够的激酶开始反应,反应的激酶浓度达到30 nM,用微量滴定板分光光度计在30oC进行30分钟,观察吸收率的降低。通过加入3.75 μl 溶于100% DMSO的VX-680 或单独DMSO,获得抑制常数。按如下公式计算Ki值,Ki = IC50/(1+[S]/Kd),[S]=[ATP]=2.2 mM, Kd=70 μM。假定作用于野生型和H396P Abl 激酶域的Kd(ATP)为70 μM,计算以上各值。

细胞实验:

[2]

  • Cell lines: CAL-62细胞
  • Concentrations: 5-500 nM
  • Incubation Time: 4天
  • Method:

    对照组CAL-62细胞培养在二甲亚砜和DMSO中,实验组加入500 nM VX-680,处理1到5天。加入不同浓度(5到500 nM) Aurora抑制剂处理不同ATC细胞4天,用来测定VX-680作用于细胞增殖的剂量依赖性。细胞在温育结束前加30 mM BrdU标记,脉冲2小时。通过比色免疫分析使用细胞增殖ELISA试剂盒分析BrdU的合并率。通过比较VX-680处理的细胞和对照组细胞得到结果,

动物实验:

[1]

  • Animal Models: 右侧腋窝处皮下注射107 HL-60白血病细胞的雌性无胸腺NCr-nu鼠
  • Dosages: 50 mg/kg, 75 mg/kg
  • Administration: 腹腔注射

溶解度(25°C)

体外

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+2% Tween 80+ddH2O

3.75 mg/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 464.59
化学式

C23H28N8OS

CAS号 639089-54-6
储存条件 3年 -20°C 粉状
2年 -80°C 溶于溶剂

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)

mg/kg g μL

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
%DMSO %

计算结果:

工作液浓度: mg/ml;

DMSO母液配制方法: mg 药物溶于μL DMSO溶液(母液浓度mg/mL,:如该浓度超过该批次药物DMSO溶解度,请先联系Selleck);

体内配方配制方法:μL DMSO母液,加入μL PEG300,混匀澄清后加入μL Tween 80,混匀澄清后加入μL ddH2O,混匀澄清。

体内配方配制方法:μL DMSO母液,加入μL Corn oil,混匀澄清。

注意:1. 首先保证母液是澄清的;
2.一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。

摩尔浓度计算器

质量 浓度 体积 分子量

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00290550 Terminated Drug: MK0457 Carcinoma Non-Small-Cell Lung Merck Sharp & Dohme LLC June 2006 Phase 2
NCT00111683 Completed Drug: MK0457 Chronic Myelogenous Leukemia in Blast Crisis|Lymphocytic Leukemia B Cell Acute|Myelodysplastic Syndromes|Myelogenous Leukemia Chronic Merck Sharp & Dohme LLC June 2005 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-08-01)

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