Tozasertib (VX-680, MK-0457)

For research use only. Not for use in humans.

目录号:S1048 中文名称:陶扎色替

Tozasertib (VX-680, MK-0457) Chemical Structure

CAS No. 639089-54-6

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。

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 3017.92 现货
RMB 3833.09 现货
RMB 4316.13 现货
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客户使用Selleck生产的Tozasertib (VX-680, MK-0457)发表文献102篇:

产品安全说明书

Aurora Kinase抑制剂选择性比较

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 NYO2SZdRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{C2PGlEPTB;MD6wNFM{QCEQvF2= NGnDdG49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
RS4-11 NILtTGZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEn2eGNKSzVyPUCuNFA1ODRizszN MkO1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
MFH-ino M3rUTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4DteGlEPTB;MD6wNFk6KM7:TR?= MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O|I5PzhxJ{7TRW5IWkWUPD;hQi=>
NTERA-S-cl-D1 NEXiUG1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVvJR|UxRTBwMEG0N|Qh|ryP NV;meXVoRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
697 NHj2[|FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH:1foRKSzVyPUCuNFI1PzFizszN NVXufmV2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
NALM-6 NILpXHNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV\xXGlZUUN3ME2wMlAzPTV{IN88US=> NVvD[oc{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
ES8 MkjZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWixbpBCUUN3ME2wMlA1PjF|IN88US=> MnXBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
HUTU-80 M2PxeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkfKTWM2OD1yLkC1Nlk6KM7:TR?= MkjWQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
MV-4-11 NWPNUIRCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVnJR|UxRTBwMEe3PFIh|ryP Mn7OQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
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BV-173 NEW1dotIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYjJR|UxRTBwMUK2OFEh|ryP NIC1bG09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
TE-11 NUD0U|hET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1v3XmlEPTB;MD6xOFk5OiEQvF2= MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O|I5PzhxJ{7TRW5IWkWUPD;hQi=>
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SIG-M5 Mm\ZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1rGRmlEPTB;MD6xOlcxPyEQvF2= M4j6WlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
OCUB-M MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NICzR|FKSzVyPUCuNVY6QDNizszN NX\ac|loRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
K052 MmTuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWfyUWpmUUN3ME2wMlE6PDhizszN NWXifIpHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
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LB647-SCLC NGjZcZhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mo\oTWM2OD1yLkKxOVI{KM7:TR?= NFG3T3o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
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MOLT-4 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIKzbZVKSzVyPUCuNlM{OzdizszN MnGxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
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HCT116 NXSyeJJMTnWwY4Tpc44h[XO|YYm= NWniU2J7OyCqcoO= M{HIemlvcGmkaYTpc44hd2ZiQYXyc5JiKEJicHjvd5Bpd3K7bHH0bY9vKGG2IGTodlI{OiC{ZYPp[JVmKGmwIHj1cYFvKEiFVEGxOkBk\WyuczD1dEB1dyBzIIXNJIFnfGW{IEOgbJJ{KGK7IGfld5Rmem5iYnzveEBu\XSqb3S= MkOwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzBzNEO0NlMoRjNyMUSzOFI{RC:jPh?=
Sf9 MlX2SpVv[3Srb36gZZN{[Xl? M17oVGlvcGmkaYTpc44hd2ZiR2PUMZRi\2enZDDBWXJQWkFiQTCoeY5sdm:5bjDvdolocW5rIHX4dJJme3OnZDDpckBj[WO3bH;2bZJ2eyCrbn\lZ5Rm\CCVZkmgZ4VtdHNidYPpcochVUKSIHHzJJN2[nO2cnH0[UwhUUN3ME2wMlAzO87:TR?= NFP4eXM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MEKzOFk5Pyd-M{CyN|Q6QDd:L3G+
HeLa NH71RYpHfW6ldHnvckBie3OjeR?= M1\JcFEzKGi{cx?= M4TK[2lvcGmkaYTpc44hd2ZiQYXyc5JiKEFicHjvd5Bpd3K7bHH0bY9vKGG2IGTodlI5QCC{ZYPp[JVmKGmwIHj1cYFvKEinTHGgZ4VtdHNiYX\0[ZIhOTJiaILzJIJ6KEWOSWPBMEBKSzVyPUCuNFE{|ryP MlzsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB3MEKxNVUoRjNyNUCyNVE2RC:jPh?=
HeLa NVnmUFloTnWwY4Tpc44h[XO|YYm= NIXRTGUyOiCqcoO= NIq4doFKdmirYnn0bY9vKG:oIFH1do9z[SCEIIDoc5NxcG:{eXzheIlwdiCjdDDUbJIzOzJicnXzbYR2\SCrbjDoeY1idiCKZVzhJINmdGy|IHHmeIVzKDF{IHjyd{BjgSCHTFnTRUwhUUN3ME2wMlE1QM7:TR?= MoLuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB3MEKxNVUoRjNyNUCyNVE2RC:jPh?=
A549 M3;ZV2FvfGmycn;sbYZmemG2aY\lJIF{e2G7 Mm\IOFghcHK| MnXxRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCDNUS5JINmdGy|IHHmeIVzKDR6IHjyd{BjgSCPVGSgZZN{[XluIFfJOVA:OzVwON88US=> NIXnSFA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MEWwNlEyPSd-M{C1NFIyOTV:L3G+
LoVo NE\je4ZCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= MlXoOFghcHK| M2ixRWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTH;Wc{Bk\WyuczDh[pRmeiB2ODDodpMh[nliTWTUJIF{e2G7LDDHTVUxRTR3LkROwG0> NHnyVIM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MEWwNlEyPSd-M{C1NFIyOTV:L3G+
HeLa MkDlRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? NIi0SHg1QCCqcoO= MlTrRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDoeY1idiCKZVzhJINmdGy|IHHmeIVzKDR6IHjyd{BjgSCPVGSgZZN{[XluIFfJOVA:PDZwMt88US=> NYnse4VMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{C1NFIyOTVpPkOwOVAzOTF3PD;hQi=>
HeLa NWjD[XFtS2WubDDjfYNt\SCjc4PhfS=> MlHLOUB2VQ>? NETYbVcyOiCqcoO= NIXDenZE\WyuIHP5Z4xmKGG{cnXzeEBqdiCqdX3hckBJ\UyjIHPlcIx{KGG|c3Xzd4VlKGG|IHTlZ5Jm[XOnIHnuJIN6[2yrbjDCNUBxem:2ZXnuJIV5eHKnc4Ppc44h[XRiNTD1UUBi\nSncjCxNkBpenNiYomgW4V{fGW{bjDicI91KGGwYXz5d4l{ MojDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB3MEKxNVUoRjNyNUCyNVE2RC:jPh?=
HeLa M1XGdmNmdGxiY4njcIUh[XO|YYm= NWTmbZdtPSC3TR?= NXLtT2NTOTJiaILz M2rTcmNmdGxiY4njcIUh[XK{ZYP0JIlvKGi3bXHuJGhmVGFiY3XscJMh[XO|ZYPz[YQh[XNiZHXjdoVie2ViaX6gZ4RkOiCycn;0[YlvKGW6cILld5Nqd25iYYSgOUB2VSCjZoTldkAyOiCqcoOgZpkhX2W|dHXyckBjdG:2IHHuZYx6e2m| NEjtbW49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MEWwNlEyPSd-M{C1NFIyOTV:L3G+
HeLa MWDGeY5kfGmxbjDhd5NigQ>? MmGyOUB2VQ>? NVPtXFlMOTJiaILz M4LYdGlvcGmkaYTpc44hd2ZiQYXyc5JiKEFicHjvd5Bpd3K7bHH0bY9vKGG2IGTodlI5QCC{ZYPp[JVmKGmwIHj1cYFvKEinTHGgZ4VtdHNiYYSgOUB2VSCjZoTldkAyOiCqcoOgZpkhX2W|dHXyckBjdG:2IHHuZYx6e2m| MmLXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB3MEKxNVUoRjNyNUCyNVE2RC:jPh?=
HeLa M2DGNmZ2dmO2aX;uJIF{e2G7 M1XJ[FUhfU1? MoHlNVIhcHK| NUjLb3loUW6qaXLpeIlwdiCxZjDBeZJwemFiQjDwbI9{eGixconsZZRqd25iYYSgWIhzOjN{IILld4llfWViaX6gbJVu[W5iSHXMZUBk\WyuczDheEA2KHWPIHHmeIVzKDF{IHjyd{BjgSCZZYP0[ZJvKGKub4SgZY5idHm|aYO= NH7Uc3A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9|MEWwNlEyPSd-M{C1NFIyOTV:L3G+
A549 NIrEZmhCdnSrcILvcIln\XKjdHn2[UBie3OjeR?= M4jZNFQ5KGi{cx?= M4nUWWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iQUW0PUBk\WyuczDh[pRmeiB2ODDodpMh[nliTWTUJIF{e2G7LDDJR|UxRTN3LklOwG0> MlfXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB5MkixNVIoRjNyN{K4NVEzRC:jPh?=
LoVo M4\wNGFvfGmycn;sbYZmemG2aY\lJIF{e2G7 NFjxbFE1QCCqcoO= NUXSbHYzSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDMc3ZwKGOnbHzzJIFnfGW{IES4JIhzeyCkeTDNWHQh[XO|YYmsJGlEPTB;NEWuN:69VQ>? NXf3UG5TRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{C3NlgyOTJpPkOwO|I5OTF{PD;hQi=>
HeLa MoDGRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl? NYfQOW96PDhiaILz MULBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEinTHGgZ4VtdHNiYX\0[ZIhPDhiaILzJIJ6KE2WVDDhd5NigSxiSVO1NF01Pi5{zszN MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODd{OEGxNkc,OzB5MkixNVI9N2F-

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
DLK / p-MKK7 / MKK7 / p-JNK / JNK ; 

PubMed: 23431148     


Western blot of the DLK pathway members in RGCs (retinal ganglion cells) 4 h after immunopanning in the presence of 0, 0.03, 0.06, 0.125, 0.25, 0.5, 1, or 2 μM tozasertib. 

p-AURKA / AURKA / Survivin ; 

PubMed: 28218735     


BGC823 cells were incubated with indicated doses of VX-680 for 24 h before subjected to western blotting with the indicated antibodies. Densitometry was used to quantify the Survivin and GAPDH levels. The relative expression shown (right panel) are means±s.e.m. of the ratios of Survivin to GAPDH. 

YAP; 

PubMed: 31160567     


Western blot analysis of YAP protein level in A549 cells treated with indicated doses of VX-680 for 24 h. 

p-AKT / p-GSK3β / Cleaved caspase-3 / Cleaved PARP ; 

PubMed: 21600017     


NB4-R2 cells were collected, lysed and subjected to Western blot analysis with cleaved caspase-3, cleaved-PARP, pAkt-1 (Ser473), pGSK-3β (Ser9) specific antibodies. GAPDH was used as a loading control. Data shown is a representative of three independent experiments.

23431148 28218735 31160567 21600017
Immunofluorescence
α-tubulin / Aurora-A ; 

PubMed: 21600017     


The morphology of mitotic spindle was shown by immunofluorescence staining with anti-α-tubulin antibody and anti-Aur-A antibodies. Microtubules were stained as green, Aur-A protein as red, and nucleus as blue.

21600017
Growth inhibition assay
Cell viability; 

PubMed: 21600017     


VX-680 significantly suppresses the proliferation in a number of leukemic cell types. OCI-AML3, NB4, HL-60 and ML-1 cells were incubated with increasing doses of VX-680 (1, 2, 5 and 10 nM) for 24 hr. Cell viability was measured by MTT assay. Data summarized three independent experiments, *p < 0.05, **p < 0.01, compared to control.

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]

- 合并

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]

- 合并
  • 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,


    (Only for Reference)
动物实验:

[1]

- 合并
  • 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
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 93 mg/mL (200.17 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+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 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
NCT00290550 Terminated Drug: MK0457 Carcinoma Non-Small-Cell Lung Merck Sharp & Dohme Corp. 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 Corp. June 2005 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

Aurora Kinase Signaling Pathway Map

Aurora Kinase Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID