Silmitasertib (CX-4945)

目录号:S2248

仅限科研使用

Silmitasertib (CX-4945)是有效的,选择性CK2(casein kinase 2)抑制剂,无细胞试验中IC50为1 nM,对 Flt3, Pim1 和 CDK1作用效果稍弱(细胞试验中没有活性)。Silmitasertib可诱导自噬并促进细胞凋亡。Phase 1/2。

Silmitasertib (CX-4945) Chemical Structure

CAS: 1009820-21-6

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 2381.77 现货
RMB 1418.29 现货
RMB 2604.97 现货
RMB 7289.1 现货
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客户使用Selleck生产的Silmitasertib (CX-4945)发表文献103篇:

产品安全说明书

Casein Kinase抑制剂选择性比较

生物活性

产品描述 Silmitasertib (CX-4945)是有效的,选择性CK2(casein kinase 2)抑制剂,无细胞试验中IC50为1 nM,对 Flt3, Pim1 和 CDK1作用效果稍弱(细胞试验中没有活性)。Silmitasertib可诱导自噬并促进细胞凋亡。Phase 1/2。
特性 CX-4945是促进人类临床实验的CK2的第一个口服生物相容性小分子抑制剂。
靶点
CK2 [1]
(Cell-free assay)
1 nM
体外研究

CX-4945是CK2特异的抑制剂,它只抑制238种激酶中的7种并且在0.5 μM浓度时它的抑制率超过90%,这是CK2的IC50的500多倍。虽然在无细胞系统中CX-4945抑制FLT3, PIM1和CDK1的IC50分别为35 nM, 46 nM和56 nM,但是在细胞基础上的功能实验中10 μM的CX-4945对FLT3, PIM1和 CDK1抑制作用不强。CX-4945有广谱的抗恶性细胞增生活性。乳腺癌细胞系对CX-4945敏感性最广泛,其EC50为1.71-20.01 μM。CX-4945的抗恶性细胞增生活性与CK2α mRNA和蛋白水平对应,但是与CK2α'催化亚基、调整CK2β亚族和PI3K/Akt 或 PTEN突变状态无关。CX-4945通过抑制CK2直接阻断Akt第129位丝氨酸的磷酸化作用来抑制PI3K/Akt信号通路,而不是通过抑制激活的PTEN起作用。用CX-4945处理可以引起磷酸化p21 (T145)减少,而p21和p27整体水平则会升高,同时诱导caspase 3/7活性。用CX-4945处理会诱导BT-474细胞阻断在细胞周期的G2/M期和BxPC-3细胞阻断在G1期。CX-4945会抑制HUVEC的增殖、迁移及血管新生,其IC50分别是5.5 μM, 2 μM和4 μM。在含氧量低的情况下BT-474和BxPC-3细胞用CX-4945处理,能阻断p53和pVHL下调,降低HIF-1α的转录活性[1]。在Jurkat细胞中CX-4945能有效抑制内源细胞内的内源CK2的活性,其IC50是0.1 μM [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A431  M3H0RWZ2dmO2aX;uJGF{e2G7 MlK5NVAh|ryP MV[zNEBucW5? Ml;yZZR1\W63YYTld{BRUTONLVHreE1uXE:UIIPp[45idGmwZx?= M2XiWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{i3PVg5Lz5{MkO4O|k5QDxxYU6=
H2170  M37WVWZ2dmO2aX;uJGF{e2G7 M13MN|ExKM7:TR?= MXWzNEBucW5? M{OzfoF1fGWwdXH0[ZMhWEl|Sz3Bb5QudVSRUjDzbYdv[Wyrbne= NH7QNHU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkO4O|k5QCd-MkKzPFc6QDh:L3G+
A431  NF\pXJRHfW6ldHnvckBCe3OjeR?= NFv0NmUyOCEQvF2= Mm\iOE0zPCCq NHjnUGpmdmijbnPld{BieG:ydH;zbZMhf2m2aDDldoxwfGmwaXK= MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN6N{m4PEc,OjJ|OEe5PFg9N2F-
H2170  M1fodmZ2dmO2aX;uJGF{e2G7 NW[5emIxOTBizszN Mm\zOE0zPCCq NH\abIVmdmijbnPld{BieG:ydH;zbZMhf2m2aDDldoxwfGmwaXK= MoDzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ|OEe5PFgoRjJ{M{i3PVg5RC:jPh?=
LNCap M4e3cmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGfQR2wxNTNyIN88US=> MnfKOEBl M3nObGlEPTB;ND61PeKh|ryP MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjh|MkOxOkc,OjJ6M{KzNVY9N2F-
A549 MoKzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoqzNE0{OCEQvF2= NUTE[JRRPzJiaB?= MYXEUXNQ M4jEVmlEPTB;ND6xOUDPxE1uIHnubIljcXS|IHPlcIwh\3Kxd4ToJINwdmOnboTyZZRqd25iZHXw[Y5l\W62bIm= Mn7OQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN4NUG0OFMoRjJ|NkWxOFQ{RC:jPh?=
H1299 MnLCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NI\Eb4QxNTNyIN88US=> NE\ud|U4OiCq M4frUmROW09? MUDJR|UxRTFwOECg{txONCCrbnjpZol1eyClZXzsJIdzd3e2aDDjc45k\W62cnH0bY9vKGSncHXu[IVvfGy7 MnvXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN4NUG0OFMoRjJ|NkWxOFQ{RC:jPh?=
A549 NWr2WVRDTnWwY4Tpc44hSXO|YYm= NXXD[pBWOS9zMDFOwG0> NIrlOJI1QCCq M2LJN2ROW09? MlPZcIVi\HNidH:gZUBld3OnLXTldIVv\GWwdDDk[YNz\WG|ZTDpckBPd3SlaDDy[ZBwenSncjDhZ5Rqfmm2eR?= NGPvboQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{[1NVQ1Oyd-MkO2OVE1PDN:L3G+
S-LAMA84 NHHUSnNHfW6ldHnvckBCe3OjeR?= MXWzxsDPxE1? NXzLZoRSOjRiaB?= M{fBSmROW09? MnzudoVlfWOnczDDT|Ih[WO2aY\peJk> M1PhdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEGyNVA6Lz5{NECxNlExQTxxYU6=
R-LAMA84 M162b2Z2dmO2aX;uJGF{e2G7 Mnq1N:Kh|ryP NY\IWm1LOjRiaB?= MkTjSG1UVw>? NUPwVos2emWmdXPld{BEUzJiYXP0bZZqfHl? MmnPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMUKxNFkoRjJ2MEGyNVA6RC:jPh?=
S-LAMA84 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWSyMlUuOTBizszN MV20PEBp NUf4SJE5TE2VTx?= MXfpcohq[mm2czDj[YxtKGe{b4f0bEBkd26lZX70doF1cW:wIHTldIVv\GWwdHz5 NYXWR|Z{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNVIyODlpPkK0NFEzOTB7PD;hQi=>
R-LAMA84 NHW2PXRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3Luc|IvPS1zMDFOwG0> NEjmdZg1QCCq MmT3SG1UVw>? NVTpR25HcW6qaXLpeJMh[2WubDDndo94fGhiY3;uZ4VvfHKjdHnvckBl\XCnbnTlcpRtgQ>? M4K3S|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEGyNVA6Lz5{NECxNlExQTxxYU6=
A549 NUnOO5hPTnWwY4Tpc44hSXO|YYm= M2G5dVExKM7:TR?= NIfMVmIyOi9{ND:0PEBp NUHsdFU2cW6qaXLpeJMhXEeILd8yNU1qdmS3Y3XkJI1q\3KjdHnvckBidmRiaX72ZZNqd25? MlHXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMkO5N|goRjJ2MEKzPVM5RC:jPh?=
A549 M1T0O2Z2dmO2aX;uJGF{e2G7 Mn;1N{DPxE1? MkmyOFghcA>? NH3mc3JqdmirYnn0d{BVT0ZvzsKxMYlv\HWlZXSgZYN1cX[jdHnvckBw\iCVbXHkJIFv\CCneIDy[ZN{cW:wIH;mJHNv[WmuIHHu[EBVf2m|dB?= MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB{M{mzPEc,OjRyMkO5N|g9N2F-
U-266 NXfPSVM3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYGwMVQxKM7:TR?= NHG0PJI1QCCq MVzJR|UxRTF7LkigxtVOyqB? M2PtcFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEi2OFk1Lz5{NEC4OlQ6PDxxYU6=
INA-6 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MknuNE01OCEQvF2= NVLwTVdRPDhiaB?= M1;Rd2lEPTB;Mj60NkDDvU1? NFrPOVg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEC4OlQ6PCd-MkSwPFY1QTR:L3G+
Jeko-1 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX3CcnlIOC12MDFOwG0> NXWyfGEzPDhiaB?= MkCyTWM2OD1{LkSgxtVOyqB? NW\pVIRGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPFY1QTRpPkK0NFg3PDl2PD;hQi=>
Rec-1 NV\YTWRJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4Hm[VAuPDBizszN NWTWSWwzPDhiaB?= NYm0b2t6UUN3ME2xMlQ3KML3TdMg M3zERVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEi2OFk1Lz5{NEC4OlQ6PDxxYU6=
Jurkat NIXyTmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{PXW|EuOTBizszN MV[0PEBp MX7JR|UxRTRwOTFOwG0> NHnU[mg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEK1N|AzPCd-MkSyOVMxOjR:L3G+
CEM-R NH\J[W5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2my[lEuOTBizszN MlnZOFghcA>? MlnMTWM2OD12IN88US=> M3XyXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MkWzNFI1Lz5{NEK1N|AzPDxxYU6=
CEM-S MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4q4SlEuOTBizszN MmPHOFghcA>? NYHVOoR[UUN3ME20MlYh|ryP M1;B[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MkWzNFI1Lz5{NEK1N|AzPDxxYU6=
MOLT-4 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3HHVlEuOTBizszN MXe0PEBp NE\nRWRKSzVyPUWuO{DPxE1? MkDpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR{NUOwNlQoRjJ2MkWzNFI1RC:jPh?=
PF-382 MkXWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWfRfpZIOS1zMDFOwG0> NVvuWZJEPDhiaB?= Mlf0TWM2OD12LkWg{txO NH6xPGg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEK1N|AzPCd-MkSyOVMxOjR:L3G+
ALL-SIL NWrJOY1CT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3XCfFEuOTBizszN MX20PEBp NIC1SXNKSzVyPUWuO{DPxE1? MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDJ3M{CyOEc,OjR{NUOwNlQ9N2F-
HPB-ALL M2XqTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEXEOYMyNTFyIN88US=> MofpOFghcA>? NHnr[2FKSzVyPU[uNUDPxE1? NH3RR3k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEK1N|AzPCd-MkSyOVMxOjR:L3G+
DND-41 MkDzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4\aVFEuOTBizszN NWWzdoxUPDhiaB?= MXzJR|UxRTlizszN MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDJ3M{CyOEc,OjR{NUOwNlQ9N2F-
ALL-SIL M3jHNGFxd3C2b4Ppd{BCe3OjeR?= M{TVTFUh|ryP MVOyOE81QCCq MV7pcoR2[2W|IHHwc5B1d3Orcx?= M1XuRVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MkWzNFI1Lz5{NEK1N|AzPDxxYU6=
DND-41 NV71SVJtSXCxcITvd4l{KEG|c3H5 NWHzU5B1PSEQvF2= NXfCWYxZOjRxNEigbC=> M{H0SYlv\HWlZYOgZZBweHSxc3nz M4\IUlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MkWzNFI1Lz5{NEK1N|AzPDxxYU6=
MOLT-4 M4HZW2Fxd3C2b4Ppd{BCe3OjeR?= MXm1JO69VQ>? MVmyOE81QCCq NULBXYRFcW6mdXPld{BieG:ydH;zbZM> M1zObVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MkWzNFI1Lz5{NEK1N|AzPDxxYU6=
C2C12 NFeybYRHfW6ldHnvckBCe3OjeR?= M1;a[FMh|ryP MYSxNk8zPC92ODDo MmHKbY5pcWKrdIOgeIhmKGW6cILld5Nqd25ib3[gc5N1\W:lbHHzeEBlcW[oZYLlcpRq[XSrb36gcYFzc2W{czDhcoQhSWu2IIDoc5NxcG:{eXzheIlwdg>? MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDJ7M{CxNUc,OjR{OUOwNVE9N2F-
Nalm6  MYDGeY5kfGmxbjDBd5NigQ>? NIO3cGsyOC9{MDFOwG0> NF\Ye2wzPCCq MmLidoV{fWy2czDpckBl\WO{ZXHz[YQhWFSHTjDwbI9{eGixconsZZRqd25iYYSgeIhmKEONMjD0ZZJo\XRicnXzbYR2\SCVM{iwJIFv\CClb37jc41qfGGwdDDkc5dvemWpdXzheIlwdiCxZjDQWGVPKHC{b4TlbY4h\XiycnXzd4lwdg>? M3nhVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NU[xO|kzLz5{NEW2NVc6OjxxYU6=
SUP-B15 M{Tnb2Z2dmO2aX;uJGF{e2G7 NYXFfHV1OTBxMkCg{txO MYeyOEBp MWjy[ZN2dHS|IHnuJIRm[3KnYYPl[EBRXEWQIIDoc5NxcG:{eXzheIlwdiCjdDD0bIUhS0t{IIThdodmfCC{ZYPp[JVmKFN|OECgZY5lKGOxbnPvcYl1[W62IHTve45z\We3bHH0bY9vKG:oIGDUSW4heHKxdHXpckBmgHC{ZYPzbY9v MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDV4MUe5Nkc,OjR3NkG3PVI9N2F-
Nalm6  MkDaRZBweHSxc3nzJGF{e2G7 MYi2M|ExKM7:TR?= NYLO[YRrPDhiaB?= NFvCU3lqdmS3Y3XzJIFxd3C2b4Ppdy=> M3jLZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NU[xO|kzLz5{NEW2NVc6OjxxYU6=
SUP-B15 M{i4NGFxd3C2b4Ppd{BCe3OjeR?= M2nWTVYwOTBizszN M4nweVQ5KGh? NFnD[4lqdmS3Y3XzJIFxd3C2b4Ppdy=> MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDV4MUe5Nkc,OjR3NkG3PVI9N2F-
ARPE-19 MnTGT4lv[XOnIFHzd4F6 M4G1bVUwOTBxMkCg{txO MnLBNlQwPDhiaB?= Ml7wbY5pcWKrdIOgR2szKGurbnHz[UBi[3Srdnn0fUBifCCjIHPvcoNmdnS{YYTpc44hd2ZiNdMg{txO MnPsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4OE[wPFAoRjJ2Nki2NFgxRC:jPh?=
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SK-N-SH MoS1dWhVWyCjc4PhfS=> M4H2XZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMXNJKGOnbHzz M2jEN|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
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MG 63 (6-TG R) MnP4dWhVWyCjc4PhfS=> Ml:4dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKE2JIE[zJEg3NVSJIGKpJINmdGy| M3L2TFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
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SJ-GBM2 Ml7jdWhVWyCjc4PhfS=> M1rX[JFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSj3HRm0zKGOnbHzz MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
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Rh18 M1vkZpFJXFNiYYPzZZk> MVnxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmhzODDj[Yxtew>? MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
Assay
Methods Test Index PMID
Western blot p-S6K1(T389) / S6K1 / p-S6(S235/236) / S6 p-AKT(S129) / p-AKT(T308) / p-AKT(S473) / AKT / p-ERK / ERK / TP53 / p-p21(Th145) / p21 / Bcl-xl p-Smad2 (Cytosol) / Smad2/3 (Cytosol) / Smad2/3 (Nucleus) / Twist / Snail 30683840 25798061 24023938
Immunofluorescence β-catenin E-cadherin / Vimentin 24023938
Growth inhibition assay Cell viability 30316146
体内研究 在BT-474模型中,一天两次口服25 mg/kg或75 mg/kg的CX-4945,具有强效的抗癌活性,TGI分别为88% 和97%,每组实验动物9只中有2只其肿瘤的体积大小比初期的要减少50%。在BxPC-3模型中,一天两次用75 mg/kg的CX-4945处理,TGI为93%,在治疗期结束时,有3只动物没发现还有残留的肿瘤[1]。在PC3异种移植的模型中,用25 mg/kg, 50 mg/kg或 75 mg/kg的CX-4945处理,能抑制肿瘤生长,TGI分别为19%, 40%和86%[2]

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:[2]
  • CK2激酶实验:

    将10 μL稀释缓冲液(ADB; 20 mM MOPS, pH 7.2, 25 mM β-磷酸甘油, 5 mM EGTA, 1 mM原钒酸钠和 1 mM 二硫苏糖醇),10 μL多肽底物(RRRDDDSDDD, 溶于ADB,浓度1mM)和10 μL重组的人源CK2(ααββ-全酶, 25 ng溶于ADB)混合,加入10 μL CX-4945。加入10μLATP溶液(90% 75 mM MgCl 2, 75 μM ATP (终浓度15 μM)溶于ADB; 10% [γ-33P]ATP (储存1 mCi/100 μL; 3000 Ci/mM起始反应,30 ℃反应10分钟。用100 μL的0.75%的磷酸终止反应,然后转移到磷酸纤维素滤板上过滤。每个孔用0.75%磷酸洗5次,真空抽干5分钟,再每孔加入15 μL闪烁液,然后用Wallac荧光计数器检测残留的放射性。通过对0.0001 μM 到1 μM的8个浓度的CX-4945实验结果的检测,计算出IC50。

细胞实验:[1]
  • Cell lines: SKBr3, MDA-MB-453, BT-474, ZR-75-1, MDA-MB-231, MDA-MB-468, T47D, MCF 7, Hs578T, MDA-MB-361, UACC-812, 等等
  • Concentrations: 溶于 DMSO, 终浓度 ~100 μM
  • Incubation Time: 4 天
  • Method: 在用药处理前,在合适的培养基中按每孔3000个细胞的浓度接种细胞培养24小时,然后用不同浓度的CX-4945处理细胞。接种悬浮细胞并处理相同的天数。接着孵育4天,加入Alamar Blue (20 μL, 体积比每孔10%),然后于37℃孵育4-5小时。检测荧光,激发光为530-560 nm,放射光为590 nm。
动物实验:[1]
  • Animal Models: 注射了BxPC-3 或BT-474细胞的免疫缺陷的雌鼠
  • Dosages: 25或75 mg/kg
  • Administration: 每日两次口服

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):
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 349.77
化学式

C19H12ClN3O2

CAS号 1009820-21-6
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
NCT04668209 Recruiting Drug: Silmitasertib Coronavirus University of Arizona|Senhwa Biosciences Inc. January 1 2021 Phase 2
NCT04663737 Active not recruiting Drug: Silmitasertib|Drug: SOC Covid19 Chris Recknor MD|Senhwa Biosciences Inc. December 3 2020 Phase 2
NCT03904862 Recruiting Drug: CX 4945 Medulloblastoma Childhood Pediatric Brain Tumor Consortium|St. Jude Children''s Research Hospital|National Cancer Institute (NCI) March 18 2019 Phase 1|Phase 2
NCT02128282 Completed Drug: CX-4945|Drug: Cisplatin|Drug: Gemcitabine Cholangiocarcinoma Senhwa Biosciences Inc. June 2014 Phase 1|Phase 2

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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操作手册

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常见问题及建议解决方法

问题 1:
How to reconstitute the compound (S2248) for in vivo uses?

回答:
For injection, CX-4945 can be dissolved in 2% DMSO+30% PEG 300+2% Tween 80+ddH2O at 5mg/ml clearly. When making the solution, please dissolve the compound in DMSO clearly first. If it dissolves not readily, please sonicate and warm the solution in water bath at about 45-50℃. Then add PEG and Tween. After they mixed well, dilute with water. For oral gavage, CX-4945 can be dissolved in 1% CMC Na at 30mg/ml as a homogeneous suspension. This is a common formulation for oral gavage, and is convenience to prepare.