Silmitasertib (CX-4945)

Catalog No.S2248

For research use only.

Silmitasertib (CX-4945) is a potent and selective inhibitor of CK2 (casein kinase 2) with IC50 of 1 nM in a cell-free assay, less potent to Flt3, Pim1 and CDK1 (inactive in cell-based assay). Silmitasertib induces autophagy and promotes apoptosis. Phase 1/2.

Silmitasertib (CX-4945) Chemical Structure

CAS No. 1009820-21-6

Selleck's Silmitasertib (CX-4945) has been cited by 98 publications

Purity & Quality Control

Choose Selective Casein Kinase Inhibitors

Biological Activity

Description Silmitasertib (CX-4945) is a potent and selective inhibitor of CK2 (casein kinase 2) with IC50 of 1 nM in a cell-free assay, less potent to Flt3, Pim1 and CDK1 (inactive in cell-based assay). Silmitasertib induces autophagy and promotes apoptosis. Phase 1/2.
Features First clinical inhibitor of CK2.
Targets
CK2 [1]
(Cell-free assay)
1 nM
In vitro

CX-4945 is selective for CK2, as it only inhibits 7 of the 238 kinases by more than 90% at concentration of 0.5 μM, which is 500-fold greater than the IC50 of CK2. Although in cell-free systems CX-4945 inhibits FLT3, PIM1, and CDK1 with IC50 of 35 nM, 46 nM, and 56 nM, respectively, CX-4945 treatment at 10 μM is inactive against FLT3, PIM1, and CDK1 in cell-based functional assays. CX-4945 exhibits a broad spectrum of antiproliferative activity, and the breast cancer cell lines displays the widest range of sensitivity to CX-4945 with EC50 of 1.71-20.01 μM. The antiproliferative activity of CX-4945 correlates with CK2α mRNA and protein levels but not the CK2α' catalytic subunit, the regulatory CK2β subunit, and the PI3K/Akt or PTEN mutational status. CX-4945 inhibits PI3K/Akt signaling by directly blocking the phosphorylation of Akt at Serine 129 by CK2 rather than through activation of PTEN. CX-4945 treatment causes reduced phosphorylation of p21 (T145), increased levels of total p21 and p27, and induction of caspase 3/7 activity. CX-4945 treatment induces a G2/M cell-cycle arrest in BT-474 cells and a G1 arrest in BxPC-3 cells. CX-4945 inhibits HUVEC proliferation, migration, and tube formation with IC50 of 5.5 μM, 2 μM, and 4 μM, respectively. Under hypoxic conditions in BT-474 and BxPC-3 cells, CX-4945 treatment prevents downregulation of p53 and pVHL and reduces activation of HIF-1α transcription. [1] CX-4945 potently inhibits endogenous intracellular CK2 activity with IC50 of 0.1 μM in Jurkat cells. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
A431  Mn\XSpVv[3Srb36gRZN{[Xl? NHvCPIYyOCEQvF2= Mn;PN|AhdWmw Mn2zZZR1\W63YYTld{BRUTONLVHreE1uXE:UIIPp[45idGmwZx?= NHLiVnM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkO4O|k5QCd-MkKzPFc6QDh:L3G+
H2170  NEnhdIJHfW6ldHnvckBCe3OjeR?= MoLmNVAh|ryP NVHVOVRPOzBibXnu NWC2clEx[XS2ZX71ZZRmeyCSSUPLMWFsfC2vVF;SJJNq\26jbHnu[y=> NVHwbmFbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzPFc6QDhpPkKyN|g4QTh6PD;hQi=>
A431  NUTjUpBvTnWwY4Tpc44hSXO|YYm= NHHVcXUyOCEQvF2= M{fRN|QuOjRiaB?= MkTw[Y5p[W6lZYOgZZBweHSxc3nzJJdqfGhiZYLsc5Rqdmmk NHXNUYw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkO4O|k5QCd-MkKzPFc6QDh:L3G+
H2170  NX;Oc4pxTnWwY4Tpc44hSXO|YYm= MoC1NVAh|ryP MWm0MVI1KGh? MXPlcohidmOnczDhdI9xfG:|aYOge4l1cCCncnzveIlvcWJ? M2H6SlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{M{i3PVg5Lz5{MkO4O|k5QDxxYU6=
LNCap NGG5bXVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnT5NE0{OCEQvF2= NGq4RmI1KGR? MmfOTWM2OD12LkW5xsDPxE1? Mn;KQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ6M{KzNVYoRjJ{OEOyN|E3RC:jPh?=
A549 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkTMNE0{OCEQvF2= MVu3NkBp NGnkfmZFVVOR NGLjb4tKSzVyPUSuNVUh|ryPLDDpcohq[mm2czDj[YxtKGe{b4f0bEBkd26lZX70doF1cW:wIHTldIVv\GWwdHz5 NWfhU3ZlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO2OVE1PDNpPkKzOlUyPDR|PD;hQi=>
H1299 MknrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoTFNE0{OCEQvF2= MU[3NkBp MVzEUXNQ MkDWTWM2OD1zLkiwJO69VSxiaX7obYJqfHNiY3XscEBoem:5dHigZ49v[2WwdILheIlwdiCmZYDlcoRmdnSueR?= M2fLclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NkWxOFQ{Lz5{M{[1NVQ1OzxxYU6=
A549 NHLub49HfW6ldHnvckBCe3OjeR?= NWjEcJpPOS9zMDFOwG0> NWDBZVl7PDhiaB?= NV7rSHd7TE2VTx?= NELsWGNt\WGmczD0c{BiKGSxc3Wt[IVx\W6mZX70JIRm[3KnYYPlJIlvKE6xdHPoJJJmeG:{dHXyJIFkfGm4aYT5 NEO0epA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{[1NVQ1Oyd-MkO2OVE1PDN:L3G+
S-LAMA84 M{LMe2Z2dmO2aX;uJGF{e2G7 NGDyUGc{yqEQvF2= MoHjNlQhcA>? MoXjSG1UVw>? MXLy[YR2[2W|IFPLNkBi[3Srdnn0fS=> NHrXbIE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECxNlExQSd-MkSwNVIyODl:L3G+
R-LAMA84 MmLySpVv[3Srb36gRZN{[Xl? MYGzxsDPxE1? M2HzeVI1KGh? MXnEUXNQ NFWyXFVz\WS3Y3XzJGNMOiCjY4Tpeol1gQ>? MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDBzMkGwPUc,OjRyMUKxNFk9N2F-
S-LAMA84 M{jhW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVfLZndKOi53LUGwJO69VQ>? NYfx[Yo2PDhiaB?= NV[wWYg6TE2VTx?= MmjKbY5pcWKrdIOgZ4VtdCCpcn;3eIgh[2:wY3XueJJifGmxbjDk[ZBmdmSnboTsfS=> MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDBzMkGwPUc,OjRyMUKxNFk9N2F-
R-LAMA84 NWXHXFRZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3SzbFIvPS1zMDFOwG0> M3fnNlQ5KGh? MXXEUXNQ NWLuVmJIcW6qaXLpeJMh[2WubDDndo94fGhiY3;uZ4VvfHKjdHnvckBl\XCnbnTlcpRtgQ>? MnL2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMUKxNFkoRjJ2MEGyNVA6RC:jPh?=
A549 M4W5UmZ2dmO2aX;uJGF{e2G7 NH3ORpMyOCEQvF2= M4jDUVEzNzJ2L{S4JIg> MlTJbY5pcWKrdIOgWGdHNc7{MT3pcoR2[2WmIH3p[5JifGmxbjDhcoQhcW64YYPpc44> M1rwTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEKzPVM5Lz5{NECyN|k{QDxxYU6=
A549 M2D3bWZ2dmO2aX;uJGF{e2G7 NH35TJM{KM7:TR?= M1vvNVQ5KGh? M{LoRYlvcGmkaYTzJHRITi4QskGtbY5lfWOnZDDhZ5RqfmG2aX;uJI9nKFOvYXSgZY5lKGW6cILld5Nqd25ib3[gV45icWxiYX7kJHR4cXO2 M3faOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEKzPVM5Lz5{NECyN|k{QDxxYU6=
U-266 MkHyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlrQNE01OCEQvF2= M4DINlQ5KGh? MlzrTWM2OD1zOT64JOK2VcLi MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB6NkS5OEc,OjRyOE[0PVQ9N2F-
INA-6 M3jQSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUGwMVQxKM7:TR?= M3TkRVQ5KGh? MljoTWM2OD1{LkSyJOK2VQ>? Mn\CQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyOE[0PVQoRjJ2MEi2OFk1RC:jPh?=
Jeko-1 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGfJ[JgxNTRyIN88US=> NESzW2M1QCCq MY\JR|UxRTJwNDFCuW3DqA>? MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB6NkS5OEc,OjRyOE[0PVQ9N2F-
Rec-1 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWLDPIQ3OC12MDFOwG0> MlTOOFghcA>? M3XrPGlEPTB;MT60OkDDvU4EoB?= MkfGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyOE[0PVQoRjJ2MEi2OFk1RC:jPh?=
Jurkat MlraS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{nzO|EuOTBizszN MlvOOFghcA>? M1;IfGlEPTB;ND65JO69VQ>? NIrWb289[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEK1N|AzPCd-MkSyOVMxOjR:L3G+
CEM-R M4G4R2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{f6dlEuOTBizszN MoPyOFghcA>? M3LLZWlEPTB;NDFOwG0> NVm2SnRDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSyOVMxOjRpPkK0NlU{ODJ2PD;hQi=>
CEM-S NYm1VGJUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYfl[XNSOS1zMDFOwG0> NGXVNo41QCCq MUHJR|UxRTRwNjFOwG0> M{PJTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MkWzNFI1Lz5{NEK1N|AzPDxxYU6=
MOLT-4 NIHQVpVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIXCe4EyNTFyIN88US=> MljoOFghcA>? NWSxW5kzUUN3ME21Mlch|ryP M2DxflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MkWzNFI1Lz5{NEK1N|AzPDxxYU6=
PF-382 NHzUZndIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV6xMVExKM7:TR?= NWrhUm5CPDhiaB?= M4DoOWlEPTB;ND61JO69VQ>? M{nzUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MkWzNFI1Lz5{NEK1N|AzPDxxYU6=
ALL-SIL NHjJOopIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmPRNU0yOCEQvF2= MmXCOFghcA>? MkLTTWM2OD13Lkeg{txO MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDJ3M{CyOEc,OjR{NUOwNlQ9N2F-
HPB-ALL M1PafGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXGxMVExKM7:TR?= Mo\2OFghcA>? MUDJR|UxRTZwMTFOwG0> M{S4[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MkWzNFI1Lz5{NEK1N|AzPDxxYU6=
DND-41 NGD5NZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1exfVEuOTBizszN MlvPOFghcA>? MWrJR|UxRTlizszN NUH6[HI{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSyOVMxOjRpPkK0NlU{ODJ2PD;hQi=>
ALL-SIL MVvBdI9xfG:|aYOgRZN{[Xl? MXG1JO69VQ>? NXqz[lN4OjRxNEigbC=> MWLpcoR2[2W|IHHwc5B1d3Orcx?= NXr6VXpsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSyOVMxOjRpPkK0NlU{ODJ2PD;hQi=>
DND-41 M4\4V2Fxd3C2b4Ppd{BCe3OjeR?= MX:1JO69VQ>? NXn5b29ZOjRxNEigbC=> M4PrVIlv\HWlZYOgZZBweHSxc3nz MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDJ3M{CyOEc,OjR{NUOwNlQ9N2F-
MOLT-4 MVrBdI9xfG:|aYOgRZN{[Xl? MWi1JO69VQ>? M{X4eFI1NzR6IHi= NEjTSnBqdmS3Y3XzJIFxd3C2b4Ppdy=> NXzq[W01RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSyOVMxOjRpPkK0NlU{ODJ2PD;hQi=>
C2C12 MVPGeY5kfGmxbjDBd5NigQ>? M4nXOlMh|ryP MUGxNk8zPC92ODDo MVzpcohq[mm2czD0bIUh\XiycnXzd4lwdiCxZjDvd5Rmd2OuYYP0JIRq\m[ncnXueIlifGmxbjDtZZJs\XK|IHHu[EBCc3RicHjvd5Bpd3K7bHH0bY9v M{XROVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MkmzNFEyLz5{NEK5N|AyOTxxYU6=
Nalm6  MnfnSpVv[3Srb36gRZN{[Xl? NHi5UFkyOC9{MDFOwG0> MUCyOEBp NUTFc|lbemW|dXz0d{BqdiCmZXPy[YF{\WRiUGTFUkBxcG:|cHjvdplt[XSrb36gZZQhfGinIFPLNkB1[XKpZYSgdoV{cWS3ZTDTN|gxKGGwZDDjc45kd22rdHHueEBld3ewcnXneYxifGmxbjDv[kBRXEWQIIDyc5RmcW5iZYjwdoV{e2mxbh?= MoDBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR3NkG3PVIoRjJ2NU[xO|kzRC:jPh?=
SUP-B15 NX2xO4s{TnWwY4Tpc44hSXO|YYm= MnvhNVAwOjBizszN NUfwNYllOjRiaB?= MWDy[ZN2dHS|IHnuJIRm[3KnYYPl[EBRXEWQIIDoc5NxcG:{eXzheIlwdiCjdDD0bIUhS0t{IIThdodmfCC{ZYPp[JVmKFN|OECgZY5lKGOxbnPvcYl1[W62IHTve45z\We3bHH0bY9vKG:oIGDUSW4heHKxdHXpckBmgHC{ZYPzbY9v NVPySnV2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS1OlE4QTJpPkK0OVYyPzl{PD;hQi=>
Nalm6  MknRRZBweHSxc3nzJGF{e2G7 NUDmOIliPi9zMDFOwG0> NHXwT2E1QCCq MVjpcoR2[2W|IHHwc5B1d3Orcx?= NHT0bm09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEW2NVc6Oid-MkS1OlE4QTJ:L3G+
SUP-B15 MY\BdI9xfG:|aYOgRZN{[Xl? MWC2M|ExKM7:TR?= M4HBNlQ5KGh? Mni2bY5lfWOnczDhdI9xfG:|aYO= MkT6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR3NkG3PVIoRjJ2NU[xO|kzRC:jPh?=
ARPE-19 M{fYe2tqdmG|ZTDBd5NigQ>? MnjEOU8yOC9{MDFOwG0> NX3LVnA{OjRxNEigbC=> NYWyOFNOcW6qaXLpeJMhS0t{IHvpcoF{\SCjY4Tpeol1gSCjdDDhJINwdmOnboTyZZRqd25ib3[gOeKh|ryP NXX1U4NyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS2PFYxQDBpPkK0Olg3ODhyPD;hQi=>
ARPE-19 NYDSOoo3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUmxNEDPxE1? NWewWGU3OjRvOU[gbC=> NGHiWpJFVVOR MUTpcohq[mm2czDj[YxtKGe{b4f0bEB1cW2nIHTldIVv\GWwdHz5 M33XUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2Nki2NFgxLz5{NE[4OlA5ODxxYU6=
HCT116  NXj2dZpJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYHRUlFtOTBizszN NXjFcFluOjRvOU[gbC=> MXvEUXNQ MUTpcohq[mm2czDj[YxtKGe{b4f0bEB1cW2nIHTldIVv\GWwdHz5 MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDZ6NkC4NEc,OjR4OE[wPFA9N2F-
ARPE-19 NWjKU3k{TnWwY4Tpc44hSXO|YYm= MnO4NVAh|ryP MkP6OEBp MoXMSG1UVw>? MlLoZ4F2e2W|IFXSMZN1emW|czDy[ZNxd26|ZTDveoVzKHSqZTDwMYVKTjMQsTDidoFv[2huIHL1eEBld2W|IH7veEBqdmS3Y3WgR2hQWMLi NI[wRlA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NE[4OlA5OCd-MkS2PFYxQDB:L3G+
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HCT116  NYGxNVFTSXCxcITvd4l{KEG|c3H5 MkLENVAh|ryP NXL5eZhiOjRxNEigbC=> MVHEUXNQ NWPk[5pQcW6mdXPld{BieG:ydH;zbZM> MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDZ6NkC4NEc,OjR4OE[wPFA9N2F-
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Saos-2 MVXxTHRUKGG|c3H5 NWH6ZZc2eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPhc5MuOiClZXzsdy=> NV:2bFUzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
BT-37 NXz1OllZeUiWUzDhd5NigQ>? MmHtdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUO3JINmdGy| M3XBTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
RD MlW1dWhVWyCjc4PhfS=> M{nEWJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCURDDj[Yxtew>? NFfZeo49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
SK-N-SH NWX3bW1OeUiWUzDhd5NigQ>? MmXUdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKFONLV6tV2gh[2WubIO= MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
BT-12 MV7xTHRUKGG|c3H5 NYO3VGo1eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IFLUMVEzKGOnbHzz Mn\KQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
MG 63 (6-TG R) MmrjdWhVWyCjc4PhfS=> MVjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVUdiNkOgLFYuXEdiUjmgZ4VtdHN? NFHHe4M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
NB1643 NHS5NZpyUFSVIHHzd4F6 Mn[0dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6EMU[0N{Bk\Wyucx?= M4XjfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
OHS-50 M1LmfZFJXFNiYYPzZZk> Ml7HdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKE:KUz21NEBk\Wyucx?= MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
Rh41 MX\xTHRUKGG|c3H5 NFv4[4pyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUni0NUBk\Wyucx?= M33yTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SJ-GBM2 NYWwXYpNeUiWUzDhd5NigQ>? NX23W5p1eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPKMWdDVTJiY3XscJM> NH3JcZY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
SK-N-MC MXrxTHRUKGG|c3H5 NX3kNoE1eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPLMW4uVUNiY3XscJM> MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
NB-EBc1 MlfPdWhVWyCjc4PhfS=> NW\YSZBNeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IF7CMWVD[zFiY3XscJM> NXWwTIlqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
LAN-5 NEfnVJVyUFSVIHHzd4F6 M37IOJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCOQV6tOUBk\Wyucx?= Mlu2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
Rh18 MYTxTHRUKGG|c3H5 Mn3udWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKqMUigZ4VtdHN? M1;0cFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
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
In vivo Oral administration of CX-4945 at 25 mg/kg or 75 mg/kg twice daily displays potent antitumor activity in the BT-474 model, with TGI of 88% and 97%, respectively, and 2 of 9 animals in each group showing more than 50% reduction in tumor size compared with the initial tumor volume. In the BxPC-3 model, CX-4945 treatment at 75 mg/kg twice daily shows 93% TGI with 3 animals having no evidence of tumor remaining at the end of the treatment period. [1] In PC3 xenograft model, administration of CX-4945 at 25 mg/kg, 50 mg/kg, or 75 mg/kg causes tumor growth inhibition with TGI of 19%, 40%, and 86%, respectively. [2]

Protocol (from reference)

Kinase Assay:[2]
  • CK2 Kinase Assay:

    CX-4945 is added at a volume of 10 μL to a reaction mixture comprising 10 μL of assay dilution buffer (ADB; 20 mM MOPS, pH 7.2, 25 mM β-glycerolphosphate, 5 mM EGTA, 1 mM sodium orthovanadate, and 1 mM dithiothreitol), 10 μL of substrate peptide (RRRDDDSDDD, dissolved in ADB at a concentration of 1 mM), 10 μL of recombinant human CK2 (ααββ-holoenzyme, 25 ng dissolved in ADB). Reactions are initiated by the addition of 10 μL of ATP solution (90% 75 mM MgCl2, 75 μM ATP (final ATP concentration=15 μM) dissolved in ADB; 10% [γ-33P]ATP (stock 1 mCi/100 μL; 3000 Ci/mM and maintained for 10 minutes at 30 °C. The reactions are quenched with 100 μL of 0.75% phosphoric acid and then transferred to and filtered through a phosphocellulose filter plate. After washing each well five times with 0.75% phosphoric acid, the plate is dried under vacuum for 5 minutes and, following the addition of 15 μL of scintillation fluid to each well, the residual radioactivity is measured using a Wallac luminescence counter. The IC50 values are derived from eight concentrations of CX-4945 over a range of 0.0001 μM to 1 μM.

Cell Research:[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, et al.
  • Concentrations: Dissolved in DMSO, final concentrations ~100 μM
  • Incubation Time: 4 days
  • Method: Cells are seeded at a density of 3,000 cells per well 24 hours prior to treatment, in appropriate media, and then treated with various concentrations of CX-4945. Suspensions cells are seeded and treated on the same day. Following 4 days of incubation, Alamar Blue (20 μL, 10% of volume per well) is added and the cells are further incubated at 37 °C for 4-5 hours. Fluorescence with excitation wavelength at 530-560 nm and emission wavelength at 590 nm is measured.
Animal Research:[1]
  • Animal Models: Female immunocompromised mice CrTac:Ncr-Foxn1nu injected with BxPC-3 or BT-474 cells
  • Dosages: 25 or 75 mg/kg
  • Administration: Oral gavage twice daily

Solubility (25°C)

In vitro

DMSO 16 mg/mL
(45.74 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
1% CMC Na
For best results, use promptly after mixing.

30mg/mL

Chemical Information

Molecular Weight 349.77
Formula

C19H12ClN3O2

CAS No. 1009820-21-6
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1=CC(=CC(=C1)Cl)NC2=NC3=C(C=CC(=C3)C(=O)O)C4=C2C=CN=C4

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

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)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

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

Answer:
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.

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