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Silmitasertib (CX-4945)

For research use only.

Catalog No.S2248

72 publications

Silmitasertib (CX-4945) Chemical Structure

CAS No. 1009820-21-6

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.

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Selleck's Silmitasertib (CX-4945) has been cited by 72 publications

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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\HSpVv[3Srb36gRZN{[Xl? MlSwNVAh|ryP MXqzNEBucW5? MnX0ZZR1\W63YYTld{BRUTONLVHreE1uXE:UIIPp[45idGmwZx?= NUHFU|hQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzPFc6QDhpPkKyN|g4QTh6PD;hQi=>
H2170  MXjGeY5kfGmxbjDBd5NigQ>? NYf6eGh7OTBizszN NFT1V5o{OCCvaX6= NV33dXI3[XS2ZX71ZZRmeyCSSUPLMWFsfC2vVF;SJJNq\26jbHnu[y=> NWP4Vo0yRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzPFc6QDhpPkKyN|g4QTh6PD;hQi=>
A431  M{fsbGZ2dmO2aX;uJGF{e2G7 NUG0WlRKOTBizszN NFLyfFE1NTJ2IHi= NIDZ[IlmdmijbnPld{BieG:ydH;zbZMhf2m2aDDldoxwfGmwaXK= MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjN6N{m4PEc,OjJ|OEe5PFg9N2F-
H2170  M2\4SmZ2dmO2aX;uJGF{e2G7 Mkf2NVAh|ryP NF3DS|Y1NTJ2IHi= MVzlcohidmOnczDhdI9xfG:|aYOge4l1cCCncnzveIlvcWJ? NWP6T49IRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzPFc6QDhpPkKyN|g4QTh6PD;hQi=>
LNCap NHzLcJJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnfkNE0{OCEQvF2= M3fJUFQh\A>? MmTvTWM2OD12LkW5xsDPxE1? MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjh|MkOxOkc,OjJ6M{KzNVY9N2F-
A549 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFPCRYcxNTNyIN88US=> NEj5ZXQ4OiCq NHXj[WdFVVOR MV\JR|UxRTRwMUWg{txONCCrbnjpZol1eyClZXzsJIdzd3e2aDDjc45k\W62cnH0bY9vKGSncHXu[IVvfGy7 MkXUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN4NUG0OFMoRjJ|NkWxOFQ{RC:jPh?=
H1299 M3jH[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NE\SWHMxNTNyIN88US=> NYnJcZkzPzJiaB?= NWrHRW5MTE2VTx?= NVqwOlBKUUN3ME2xMlgxKM7:TTygbY5pcWKrdIOgZ4VtdCCpcn;3eIgh[2:wY3XueJJifGmxbjDk[ZBmdmSnboTsfS=> NX36VZBlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO2OVE1PDNpPkKzOlUyPDR|PD;hQi=>
A549 MlvUSpVv[3Srb36gRZN{[Xl? M1exS|EwOTBizszN MV60PEBp NWDFToRVTE2VTx?= NWrkcGR6dGWjZIOgeI8h[SCmb4PlMYRmeGWwZHXueEBl\WO{ZXHz[UBqdiCQb4TjbEBz\XCxcoTldkBi[3Srdnn0fS=> Mn3kQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN4NUG0OFMoRjJ|NkWxOFQ{RC:jPh?=
S-LAMA84 NVPRcppHTnWwY4Tpc44hSXO|YYm= M2\2S|PDqM7:TR?= NWLDXXhYOjRiaB?= MYjEUXNQ M4Dkb5Jm\HWlZYOgR2szKGGldHn2bZR6 MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDBzMkGwPUc,OjRyMUKxNFk9N2F-
R-LAMA84 NXu2bnNvTnWwY4Tpc44hSXO|YYm= M37JdVPDqM7:TR?= MUeyOEBp MoSySG1UVw>? NG\LZ2dz\WS3Y3XzJGNMOiCjY4Tpeol1gQ>? M13ZbVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEGyNVA6Lz5{NECxNlExQTxxYU6=
S-LAMA84 MnfHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYKyMlUuOTBizszN M{TLb|Q5KGh? M3rEUWROW09? MULpcohq[mm2czDj[YxtKGe{b4f0bEBkd26lZX70doF1cW:wIHTldIVv\GWwdHz5 NGnRcYE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECxNlExQSd-MkSwNVIyODl:L3G+
R-LAMA84 MkX0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV:yMlUuOTBizszN MmHCOFghcA>? M33lRWROW09? NV7zPGwxcW6qaXLpeJMh[2WubDDndo94fGhiY3;uZ4VvfHKjdHnvckBl\XCnbnTlcpRtgQ>? NH3KOWo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECxNlExQSd-MkSwNVIyODl:L3G+
A549 MoPTSpVv[3Srb36gRZN{[Xl? NX;OflIzOTBizszN MWmxNk8zPC92ODDo MVPpcohq[mm2czDUS2Yu|rJzLXnu[JVk\WRibXnndoF1cW:wIHHu[EBqdn[jc3nvci=> NGKwUpg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NECyN|k{QCd-MkSwNlM6Ozh:L3G+
A549 MUXGeY5kfGmxbjDBd5NigQ>? M4j6RlMh|ryP MVy0PEBp NILXU2lqdmirYnn0d{BVT0ZvzsKxMYlv\HWlZXSgZYN1cX[jdHnvckBw\iCVbXHkJIFv\CCneIDy[ZN{cW:wIH;mJHNv[WmuIHHu[EBVf2m|dB?= MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB{M{mzPEc,OjRyMkO5N|g9N2F-
U-266 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MU[wMVQxKM7:TR?= MXy0PEBp MkDUTWM2OD1zOT64JOK2VcLi M{XUcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEi2OFk1Lz5{NEC4OlQ6PDxxYU6=
INA-6 MmP4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVW2blR[OC12MDFOwG0> MYG0PEBp NWn1fXdZUUN3ME2yMlQzKML3TR?= NEjXfVk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEC4OlQ6PCd-MkSwPFY1QTR:L3G+
Jeko-1 MlPkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUOwMVQxKM7:TR?= NVHYTpMyPDhiaB?= M2XrXWlEPTB;Mj60JOK2VcLi M{fTXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEi2OFk1Lz5{NEC4OlQ6PDxxYU6=
Rec-1 NF23TFhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFn2TYMxNTRyIN88US=> MX60PEBp MkT5TWM2OD1zLkS2JOK2VcLi MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB6NkS5OEc,OjRyOE[0PVQ9N2F-
Jurkat NVTXZm0zT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoHkNU0yOCEQvF2= MYm0PEBp NX60W4tUUUN3ME20Mlkh|ryP NXr5S5diRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSyOVMxOjRpPkK0NlU{ODJ2PD;hQi=>
CEM-R M{\6cWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIPl[nQyNTFyIN88US=> MknlOFghcA>? M4K2fWlEPTB;NDFOwG0> MmH3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR{NUOwNlQoRjJ2MkWzNFI1RC:jPh?=
CEM-S MmnlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1rGZVEuOTBizszN NFXYTpM1QCCq NH3TeI9KSzVyPUSuOkDPxE1? NFzXR2U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEK1N|AzPCd-MkSyOVMxOjR:L3G+
MOLT-4 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVexMVExKM7:TR?= NInxdVY1QCCq NFXEUndKSzVyPUWuO{DPxE1? M{\BblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MkWzNFI1Lz5{NEK1N|AzPDxxYU6=
PF-382 NXm1c5dIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUKxMVExKM7:TR?= M4rVW|Q5KGh? MmrQTWM2OD12LkWg{txO NGP5UpI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEK1N|AzPCd-MkSyOVMxOjR:L3G+
ALL-SIL MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn3vNU0yOCEQvF2= NF;aSG01QCCq MWjJR|UxRTVwNzFOwG0> NIDaW5k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEK1N|AzPCd-MkSyOVMxOjR:L3G+
HPB-ALL MlX5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1f5eVEuOTBizszN Ml\iOFghcA>? MXTJR|UxRTZwMTFOwG0> MknXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR{NUOwNlQoRjJ2MkWzNFI1RC:jPh?=
DND-41 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn64NU0yOCEQvF2= M4jhfFQ5KGh? Mkj3TWM2OD17IN88US=> NFnEd4o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEK1N|AzPCd-MkSyOVMxOjR:L3G+
ALL-SIL NF;TVpBCeG:ydH;zbZMhSXO|YYm= M2f6UVUh|ryP NGLjXXAzPC92ODDo NGrOfZhqdmS3Y3XzJIFxd3C2b4Ppdy=> MnG1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR{NUOwNlQoRjJ2MkWzNFI1RC:jPh?=
DND-41 MVfBdI9xfG:|aYOgRZN{[Xl? NXnLfZhXPSEQvF2= M{jaXlI1NzR6IHi= NXXBUZNFcW6mdXPld{BieG:ydH;zbZM> Mlq2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR{NUOwNlQoRjJ2MkWzNFI1RC:jPh?=
MOLT-4 Mnv3RZBweHSxc3nzJGF{e2G7 NGflb|k2KM7:TR?= MknGNlQwPDhiaB?= NGjKSnpqdmS3Y3XzJIFxd3C2b4Ppdy=> NUP4e3B[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSyOVMxOjRpPkK0NlU{ODJ2PD;hQi=>
C2C12 NFW2eGFHfW6ldHnvckBCe3OjeR?= MW[zJO69VQ>? MlW0NVIwOjRxNEigbC=> NVTudmpPcW6qaXLpeJMhfGinIHX4dJJme3Orb36gc4Yhd3O2ZX;jcIF{fCCmaX\m[ZJmdnSrYYTpc44hdWG{a3Xyd{BidmRiQXv0JJBpd3OyaH;yfYxifGmxbh?= NVj6UG9IRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSyPVMxOTFpPkK0Nlk{ODFzPD;hQi=>
Nalm6  M33iNmZ2dmO2aX;uJGF{e2G7 MoS1NVAwOjBizszN Mn;RNlQhcA>? M3TuRZJme3WudIOgbY4h\GWlcnXhd4VlKFCWRV6gdIhwe3Cqb4L5cIF1cW:wIHH0JJRp\SCFS{KgeIFz\2W2IILld4llfWViU{O4NEBidmRiY3;uZ49ucXSjboSg[I94dnKnZ4XsZZRqd25ib3[gVHRGViCycn;0[YlvKGW6cILld5Nqd25? NFjwc|I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEW2NVc6Oid-MkS1OlE4QTJ:L3G+
SUP-B15 NVvZfJhHTnWwY4Tpc44hSXO|YYm= Mne3NVAwOjBizszN NUTGSI02OjRiaB?= NWPNc414emW|dXz0d{BqdiCmZXPy[YF{\WRiUGTFUkBxcG:|cHjvdplt[XSrb36gZZQhfGinIFPLNkB1[XKpZYSgdoV{cWS3ZTDTN|gxKGGwZDDjc45kd22rdHHueEBld3ewcnXneYxifGmxbjDv[kBRXEWQIIDyc5RmcW5iZYjwdoV{e2mxbh?= NV\yZ|N{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS1OlE4QTJpPkK0OVYyPzl{PD;hQi=>
Nalm6  M1LIeWFxd3C2b4Ppd{BCe3OjeR?= NVvTNJNtPi9zMDFOwG0> MoDOOFghcA>? M2\wS4lv\HWlZYOgZZBweHSxc3nz M{faPFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NU[xO|kzLz5{NEW2NVc6OjxxYU6=
SUP-B15 MUPBdI9xfG:|aYOgRZN{[Xl? NWfrcFFqPi9zMDFOwG0> NGmwS3k1QCCq Mk\2bY5lfWOnczDhdI9xfG:|aYO= MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDV4MUe5Nkc,OjR3NkG3PVI9N2F-
ARPE-19 NY\SeWRuU2mwYYPlJGF{e2G7 MYi1M|ExNzJyIN88US=> NF7zPXAzPC92ODDo Mo\sbY5pcWKrdIOgR2szKGurbnHz[UBi[3Srdnn0fUBifCCjIHPvcoNmdnS{YYTpc44hd2ZiNdMg{txO MmLhQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4OE[wPFAoRjJ2Nki2NFgxRC:jPh?=
ARPE-19 NH\wZppIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUHKT|dMOTBizszN M4WzWlI1NTl4IHi= Mo\iSG1UVw>? NVezeWVIcW6qaXLpeJMh[2WubDDndo94fGhidHnt[UBl\XCnbnTlcpRtgQ>? M3P3[|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2Nki2NFgxLz5{NE[4OlA5ODxxYU6=
HCT116  NI\3VoFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWnZfnFjOTBizszN Mor3NlQuQTZiaB?= MU\EUXNQ M3PFc4lvcGmkaYTzJINmdGxiZ4Lve5RpKHSrbXWg[IVx\W6mZX70cJk> Mn63QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4OE[wPFAoRjJ2Nki2NFgxRC:jPh?=
ARPE-19 NUf2U|ZqTnWwY4Tpc44hSXO|YYm= MVKxNEDPxE1? M3TtcVQhcA>? MWDEUXNQ NELueFRk[XW|ZYOgSXIue3S{ZYPzJJJme3CxboPlJI93\XJidHjlJJAu\UmIMt8xJIJz[W6laDygZpV1KGSxZYOgco91KGmwZIXj[UBEUE:SwrC= NFG2[Gg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NE[4OlA5OCd-MkS2PFYxQDB:L3G+
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Saos-2 NYDhRnFNeUiWUzDhd5NigQ>? NGLvO|hyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU3Hvd{0zKGOnbHzz NX7LT4FrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
BT-37 MVTxTHRUKGG|c3H5 M3;aR5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCEVD2zO{Bk\Wyucx?= M{TuTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
RD NWTzUm45eUiWUzDhd5NigQ>? NGHzdnlyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUlSgZ4VtdHN? M4fYU|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-SH NGjhUldyUFSVIHHzd4F6 NVnzUY5QeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPLMW4uW0hiY3XscJM> Mk[0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
BT-12 MlHJdWhVWyCjc4PhfS=> MUPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSlRvMUKgZ4VtdHN? NHroUWs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
MG 63 (6-TG R) NF;yXolyUFSVIHHzd4F6 MkTGdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKE2JIE[zJEg3NVSJIGKpJINmdGy| M2rPUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
NB1643 MV3xTHRUKGG|c3H5 Mlu1dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6EMU[0N{Bk\Wyucx?= MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
OHS-50 NHnoUldyUFSVIHHzd4F6 NEH5bJZyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiT1jTMVUxKGOnbHzz NWj3RW56RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh41 MYjxTHRUKGG|c3H5 NYL3VWR6eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGLoOFEh[2WubIO= MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
SJ-GBM2 NFX4PVFyUFSVIHHzd4F6 M4XlTJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSj3HRm0zKGOnbHzz NXzucodTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
SK-N-MC MoHidWhVWyCjc4PhfS=> NH;lbnVyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1utUk1OSyClZXzsdy=> MkfsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
NB-EBc1 Ml3JdWhVWyCjc4PhfS=> NFSwe3ZyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKtSWJkOSClZXzsdy=> NUHvWop4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
LAN-5 NUL2TItueUiWUzDhd5NigQ>? NIrybFZyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTFHOMVUh[2WubIO= NYTLVXFERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh18 MmP5dWhVWyCjc4PhfS=> NIXBWFhyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUnixPEBk\Wyucx?= MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-S6K1(T389) / S6K1 / p-S6(S235/236) / S6; 

PubMed: 30683840     


DLD-1 cells were incubated with 25 μM silmitasertib for 16 h. The levels of the indicated proteins were analyzed by western blot.

p-AKT(S129) / p-AKT(T308) / p-AKT(S473) / AKT / p-ERK / ERK / TP53 / p-p21(Th145) / p21 / Bcl-xl; 

PubMed: 25798061     


CX-4945 altered PI3K/AKT/Bcl-XL, ERK/AP-1 and TP53/p21proteins in HNSCC. UM-SCC-1 (left) and UM-SCC-46 (right) cell lines were treated with 4 and 10 μM CX-4945, whole cell lysates were harvested 6 and 24 hours after treatment, and subjected to SDS-PAGE and Western blot of indicated proteins. β-action was used as a loading control.

p-Smad2 (Cytosol) / Smad2/3 (Cytosol) / Smad2/3 (Nucleus) / Twist / Snail; 

PubMed: 24023938     


The effect of CX-4945 on TGF-β1-induced activation of Smad and expression of Snail and Twist was evaluated using Western blot analysis. Briefly, after 24 h serum starvation, A549 cells were treated with TGF-β1 (5 ng/ml) alone or in combination with CX-4945 in media containing 0.1% FBS for 48 h. Cytosolic and Nuclear fractions were obtained. Actin and histone H3 were used as internal control of cytosolic and nuclear fraction, respectively. The relative, normalized ratio between p-Smad2 and actin was presented. 

30683840 25798061 24023938
Immunofluorescence
β-catenin; 

PubMed: 24023938     


Nuclear translocation of β-catenin and its inhibition by CX-4945 were confirmed by immunocytochemistry. Nuclei were counterstained with Hoechst 33342. All scale bars represent 20 µm.

E-cadherin / Vimentin; 

PubMed: 24023938     


The effect of CX-4945 on the TGF-β1-induced expression of epithelial and mesenchymal markers was evaluated by immunocytochemistry. Briefly, after 24 h serum starvation, A549 cells were treated with TGF-β1 (5 ng/ml) alone or in combination with CX-4945 in media containing 0.1% FBS for 72 h. All scale bars represent 200 µm.

24023938
Growth inhibition assay
Cell viability; 

PubMed: 30316146     


CX-4945 decreases cell viability of HuCCT1, EGI-1, and Liv27 CCA cell lines in dose-dependent manner (IC50of 7.3, 9.5, and 9.4 μM, respectively) (A)

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

Kinase Assay:[2]
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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]
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  • 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.
    (Only for Reference)
Animal Research:[1]
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  • 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
    (Only for Reference)

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

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 349.77
Formula

C19H12ClN3O2

CAS No. 1009820-21-6
Storage powder
in solvent
Synonyms N/A
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)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
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Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

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*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

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    C2=C1/X C2: LOG(C2):
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Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

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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

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

  • * Indicates a Required Field

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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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID