Tozasertib (VX-680, MK-0457)

For research use only.

Catalog No.S1048

99 publications

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

CAS No. 639089-54-6

Tozasertib (VX-680, MK-0457) is a pan-Aurora inhibitor, mostly against Aurora A with Kiapp of 0.6 nM in a cell-free assay, less potent towards Aurora B/Aurora C and 100-fold more selective for Aurora A than 55 other kinases. The only exceptions are Fms-related tyrosine kinase-3 (FLT-3) and BCR-ABL tyrosine kinase, which are inhibited by the Tozasertib with both Ki of 30 nM. Tozasertib induces apoptosis and autophagy. Phase 2.

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Selleck's Tozasertib (VX-680, MK-0457) has been cited by 99 publications

Purity & Quality Control

Choose Selective Aurora Kinase Inhibitors

Biological Activity

Description Tozasertib (VX-680, MK-0457) is a pan-Aurora inhibitor, mostly against Aurora A with Kiapp of 0.6 nM in a cell-free assay, less potent towards Aurora B/Aurora C and 100-fold more selective for Aurora A than 55 other kinases. The only exceptions are Fms-related tyrosine kinase-3 (FLT-3) and BCR-ABL tyrosine kinase, which are inhibited by the Tozasertib with both Ki of 30 nM. Tozasertib induces apoptosis and autophagy. Phase 2.
Targets
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)
In vitro

Although its multi-kinase profile, VX-680 induces similar cytotoxicity with IC50 of approximately 300 nM and exhibits an AUR B-like inhibitory phenotype of G2/M arrest, endoreduplication and apoptosis in BaF3 cells transfected with ABL or FLT-3 (mutant and wild type) kinases. VX-680 prevents the CAL-62 proliferation in a time-dependent manner. VX-680 treatment for 14 days significantly decreases the number and size of colonies by approximately 70% in the 8305C and 90% in the CAL-62, 8505C and BHT-101. Treatment of the different ATC cells with VX-680 inhibits proliferation with the IC50 between 25 and 150  nM. The VX-680 significantly impairs the ability of the different cell lines to form colonies in soft agar. Analysis of caspase-3 activity indicates that VX-680 induces apoptosis in the different cell lines. CAL-62 cells exposed for 12  hours to VX-680 showed an accumulation of cells with ≥4N DNA content. Time-lapse analysis demonstrates that VX-680-treated CAL-62 cells exit metaphase without dividing. Moreover, histone H3 phosphorylation is abrogated following VX-680 treatment. [2] VX-680 has significant inhibitory activity against BCR-Abl bearing the T315I mutation in patient-derived samples. [3]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BE-13 M1LjNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWTBeWszUUN3ME2wMlAxOzN6IN88US=> NVWzSZZyW0GQR2LFVi=>
RS4-11 M{PJZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mmf3TWM2OD1yLkCwOFA1KM7:TR?= M3vuZXNCVkeURWK=
MFH-ino M37qTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3XZVGlEPTB;MD6wNFk6KM7:TR?= M33DUHNCVkeURWK=
NTERA-S-cl-D1 NV[0T|d1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MW\JR|UxRTBwMEG0N|Qh|ryP NIH1bplUSU6JUlXS
697 NGj3OolIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVLKOFl[UUN3ME2wMlAzPDdzIN88US=> M3HkdHNCVkeURWK=
NALM-6 NEG3eJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml\ZTWM2OD1yLkCyOVUzKM7:TR?= M3XlOXNCVkeURWK=
ES8 NXXjTFJWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHTsN3lKSzVyPUCuNFQ3OTNizszN MnG0V2FPT1KHUh?=
HUTU-80 NUOwO|k6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEfrXZdKSzVyPUCuNFUzQTlizszN MlPZV2FPT1KHUh?=
MV-4-11 NYD3fFNGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1LQR2lEPTB;MD6wO|c5OiEQvF2= NWPNNpFlW0GQR2LFVi=>
MONO-MAC-6 MoTOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1XPXGlEPTB;MD6wO|g4QSEQvF2= NWiwNmJYW0GQR2LFVi=>
LC-2-ad MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYqw[IJTUUN3ME2wMlA5Pzh7IN88US=> MYTTRW5IWkWU
BL-41 NVnlNJJDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHnncHhKSzVyPUCuNVA1PDVizszN NILC[HFUSU6JUlXS
A4-Fuk MmfuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NI\4b3FKSzVyPUCuNVE2PjNizszN MX;TRW5IWkWU
SW954 M2GwV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYXJR|UxRTBwMUKyNlkh|ryP NHuzfVRUSU6JUlXS
BV-173 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVLOPXFYUUN3ME2wMlEzPjRzIN88US=> M2nwVHNCVkeURWK=
TE-11 NGfWWJRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYHC[nhjUUN3ME2wMlE1QTh{IN88US=> M4LKeXNCVkeURWK=
SK-UT-1 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1zGSWlEPTB;MD6xOVk3PSEQvF2= MXnTRW5IWkWU
SIG-M5 NUfYSGM1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MonUTWM2OD1yLkG2O|A4KM7:TR?= MUHTRW5IWkWU
OCUB-M MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3r0SWlEPTB;MD6xOlk5OyEQvF2= Mm\SV2FPT1KHUh?=
K052 Mnn4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFvaXWZKSzVyPUCuNVk1QCEQvF2= MWPTRW5IWkWU
VA-ES-BJ MnrkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXnJR|UxRTBwMkCwPFYh|ryP M2OzT3NCVkeURWK=
SW982 NXH3ZVlST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEnBV5lKSzVyPUCuNlE{QCEQvF2= M4jBcnNCVkeURWK=
LB647-SCLC NF[x[o1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUTuO5VoUUN3ME2wMlIyPTJ|IN88US=> M{\3XXNCVkeURWK=
PSN1 NF7p[4ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXfEdJd{UUN3ME2wMlIzODJ4IN88US=> M2\PTnNCVkeURWK=
BB30-HNC MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXTJR|UxRTBwMkK1PVEh|ryP Mnu1V2FPT1KHUh?=
ST486 Ml7FS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXLJR|UxRTBwMkOwPFch|ryP NGLEdG1USU6JUlXS
MOLT-4 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHv2PVRKSzVyPUCuNlM{OzdizszN NV;JfI9zW0GQR2LFVi=>
EW-16 M2DhdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXOyW4ZCUUN3ME2wMlI{PzZ6IN88US=> MnHTV2FPT1KHUh?=
KS-1 NGi2ZnZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV\JR|UxRTBwMkO3PFUh|ryP MVrTRW5IWkWU
SR MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVTt[GpMUUN3ME2wMlI1PTZ2IN88US=> M1;4cHNCVkeURWK=
KM12 M{DnOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUXJR|UxRTBwMk[zOkDPxE1? M3jRXHNCVkeURWK=
EM-2 NWDEfHN6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWnJR|UxRTBwMk[2OFEh|ryP MmnZV2FPT1KHUh?=
MEG-01 NGfQbpNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkT4TWM2OD1yLkK3PFQ6KM7:TR?= M2frRnNCVkeURWK=
NB13 NF\rTI5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX7JR|UxRTBwMke5PFQh|ryP MkPHV2FPT1KHUh?=
RKO NV;pXFkyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV;JR|UxRTBwM{C4NVMh|ryP NFLBSHRUSU6JUlXS
CESS MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUnNfVF[UUN3ME2wMlMyOzJ6IN88US=> NYLTTG5[W0GQR2LFVi=>
EoL-1-cell MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3vGbWlEPTB;MD6zN|Q2QSEQvF2= NHXwdo1USU6JUlXS
DOHH-2 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYfJR|UxRTBwM{O3PFEh|ryP MkDxV2FPT1KHUh?=
A388 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX;JR|UxRTBwM{SwPFYh|ryP MnvuV2FPT1KHUh?=
LAMA-84 NVW4co5FT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHrnXVRKSzVyPUCuN|UyPzhizszN MkfZV2FPT1KHUh?=
IMR-5 Mn\kS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoW1TWM2OD1yLkO1OVQh|ryP M1:2eHNCVkeURWK=
KARPAS-422 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFe5RplKSzVyPUCuN|czPzJizszN M2fW[3NCVkeURWK=
MRK-nu-1 Mo\qS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXHJR|UxRTBwM{ixN{DPxE1? NFr6WVhUSU6JUlXS
BL-70 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEXwXlBKSzVyPUCuN|g6PzRizszN NULaPVB6W0GQR2LFVi=>
LXF-289 M4PBOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoXPTWM2OD1yLkSwOFA3KM7:TR?= MUTTRW5IWkWU
RL95-2 NX;KfI16T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVXJR|UxRTBwNEC1Olch|ryP MYrTRW5IWkWU
QIMR-WIL MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXvVWZg2UUN3ME2wMlQzPjd4IN88US=> M4D2UnNCVkeURWK=
K-562 MlTRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4DJ[WlEPTB;MD60N|Q4OiEQvF2= NFjyXZFUSU6JUlXS
NCI-H510A Ml;jS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFTUdIpKSzVyPUCuOFM5OjNizszN NE\CSnBUSU6JUlXS
NCI-H524 NGHKR29Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml\DTWM2OD1yLkWxNVQ4KM7:TR?= MYnTRW5IWkWU
KE-37 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHTWcXVKSzVyPUCuOVIyODJizszN NWnsUmI4W0GQR2LFVi=>
KP-N-YS M2jQb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYXMe4M3UUN3ME2wMlU1Ozl{IN88US=> MkPVV2FPT1KHUh?=
LS-411N MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUHJR|UxRTBwNUe3OVIh|ryP M{\NNXNCVkeURWK=
CTV-1 MnruS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUTJR|UxRTBwNUi3O|Mh|ryP MWnTRW5IWkWU
NCI-SNU-16 NHjHTJlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIqweHFKSzVyPUCuOlM2PzFizszN Mly2V2FPT1KHUh?=
HT-144 M33ifmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV;Y[ZpOUUN3ME2wMlY{Pzl6IN88US=> NHjES4JUSU6JUlXS
NCI-H187 NHHqbXFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4XKO2lEPTB;MD62OFE{KM7:TR?= MYjTRW5IWkWU
OCI-AML2 NEnSbXJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUf4cYhuUUN3ME2wMlY1PDB|IN88US=> M2PXcnNCVkeURWK=
CCRF-CEM NILubJhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV\JR|UxRTBwNkWzOFYh|ryP MX\TRW5IWkWU
ONS-76 MmjJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWHhcGN4UUN3ME2wMlY3PDV6IN88US=> NHTTRpRUSU6JUlXS
IST-SL2 M1;6S2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3fBR2lEPTB;MD63NVk5OiEQvF2= M17NVHNCVkeURWK=
NB6 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH\wWXJKSzVyPUCuO|czPTRizszN MWfTRW5IWkWU
SK-PN-DW MkfTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEntSZRKSzVyPUCuO|kyPCEQvF2= M3HYTHNCVkeURWK=
HCC1599 NIWyRnBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmGyTWM2OD1yLkiwPFc1KM7:TR?= MWfTRW5IWkWU
MC116 NGHjeI5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3ixRmlEPTB;MD64OVAyOSEQvF2= Ml:yV2FPT1KHUh?=
TE-15 M1PrU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnnqTWM2OD1yLki1NFk5KM7:TR?= MUHTRW5IWkWU
HOP-62 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4i5bGlEPTB;MD64OlMzQSEQvF2= M2XCUnNCVkeURWK=
TGBC24TKB M1KwNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3r5TGlEPTB;MD64OlM5PSEQvF2= MYnTRW5IWkWU
HCE-4 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2frTWlEPTB;MD64PFA3OyEQvF2= M2nSTnNCVkeURWK=
ALL-PO MofYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmL0TWM2OD1yLki4NVc2KM7:TR?= NXi5Uol3W0GQR2LFVi=>
KGN M4PlUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MY\JR|UxRTBwOEm5PVUh|ryP NH;MfnBUSU6JUlXS
ML-2 MnG0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1i4TGlEPTB;MD65NFI2QSEQvF2= MX7TRW5IWkWU
ES4 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXPP[mZyUUN3ME2wMlkyOTJ6IN88US=> MmLFV2FPT1KHUh?=
SF126 M4PicGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkHiTWM2OD1yLkm0PFE6KM7:TR?= M4TDXHNCVkeURWK=
SK-N-DZ NH;Kem1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmfLTWM2OD1yLkm2NVg6KM7:TR?= MlHWV2FPT1KHUh?=
HCC1187 NIX1cZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV;JR|UxRTFwMEC1NFUh|ryP MoTmV2FPT1KHUh?=
DU-4475 MmjOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MonjTWM2OD1zLkCxO|U3KM7:TR?= NHXLc5ZUSU6JUlXS
NKM-1 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUHWRpBMUUN3ME2xMlAzPzd3IN88US=> NEH1OGZUSU6JUlXS
HL-60 M1jIdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MofkTWM2OD1zLkC2OVc1KM7:TR?= NH30U5RUSU6JUlXS
SBC-1 NHvWO2xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHflUopKSzVyPUGuNVI2PDJizszN MonGV2FPT1KHUh?=
TE-10 M{DtW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1jSPGlEPTB;MT6xNlk1PiEQvF2= Mn\IV2FPT1KHUh?=
ETK-1 NI\DPItIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYDJR|UxRTFwMUO2NVMh|ryP Ml3oV2FPT1KHUh?=
HAL-01 NYrH[FNKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3vHbmlEPTB;MT6xOlcxQSEQvF2= M1nlenNCVkeURWK=
BB65-RCC M2[yXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoPSTWM2OD1zLkG4NFA2KM7:TR?= MnfGV2FPT1KHUh?=
EW-1 NYnBVmc2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3nJSmlEPTB;MT6xPFU3OiEQvF2= MnTGV2FPT1KHUh?=
SK-NEP-1 MkfSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHrsU2pKSzVyPUGuNlEyOTFizszN M2PRO3NCVkeURWK=
SK-LMS-1 M2Lncmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1fDPGlEPTB;MT6yNlIyOiEQvF2= NGjKbGpUSU6JUlXS
DEL NFvTdWRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGjhdJBKSzVyPUGuNlU3PDNizszN NV\BN3hiW0GQR2LFVi=>
GT3TKB M1m3[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH\IOFdKSzVyPUGuNlgxPTdizszN NI\SeYlUSU6JUlXS
MOLT-16 M3G1PWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1XGUmlEPTB;MT6zOVQxPSEQvF2= MWDTRW5IWkWU
CMK MnzGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoPQTWM2OD1zLkSyNVE4KM7:TR?= NVTpRZVCW0GQR2LFVi=>
NB5 NIj3SmRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUHlZ5RbUUN3ME2xMlY1OjJ7IN88US=> NVLrfHRDW0GQR2LFVi=>
NCI-H1963 NFfIZ3BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXTJR|UxRTFwN{C1PFMh|ryP MVjTRW5IWkWU
KURAMOCHI MlLiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXnJR|UxRTFwN{i5NVEh|ryP NYrLUGt[W0GQR2LFVi=>
TE-8 Mo[2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWj0d|d3UUN3ME2xMlgxOzZ6IN88US=> MnzVV2FPT1KHUh?=
NCI-H1304 NXPIXWc3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV7JR|UxRTFwOEOwO|Mh|ryP MUXTRW5IWkWU
A101D Ml7yS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnT5TWM2OD1zLki3N|k2KM7:TR?= NHS0OmhUSU6JUlXS
SCLC-21H NXv5XpJCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXLFdIZyUUN3ME2xMlk4ODV5IN88US=> MWXTRW5IWkWU
GB-1 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlS2TWM2OD1{LkCxOlQ4KM7:TR?= NX\tTZBbW0GQR2LFVi=>
KARPAS-45 NI\Jb4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlzSTWM2OD1{LkCyOlU1KM7:TR?= NW\IZnNMW0GQR2LFVi=>
ATN-1 M4jEbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MonYTWM2OD1{LkCyPFU5KM7:TR?= MnjFV2FPT1KHUh?=
NCI-H720 MnX5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWTJR|UxRTJwME[yOFQh|ryP M{G2PXNCVkeURWK=
RPMI-6666 NFL5[21Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV3JR|UxRTJwMU[yNFch|ryP Ml7JV2FPT1KHUh?=
NB17 M3jSXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoT4TWM2OD1{LkK5Nlch|ryP NFzlPVdUSU6JUlXS
IST-SL1 NVLvcVlVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYn4fnB3UUN3ME2yMlI6PzZ3IN88US=> NVnFbWF3W0GQR2LFVi=>
SH-4 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mlv1TWM2OD1{LkOyOFY6KM7:TR?= MlfrV2FPT1KHUh?=
K5 M1:yO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{f1dGlEPTB;Mj60NFMyQSEQvF2= M2fSUnNCVkeURWK=
OVCAR-4 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3OyOGlEPTB;Mj60OlE{KM7:TR?= MnniV2FPT1KHUh?=
ACN NFTyfYlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVPWSVB{UUN3ME2yMlUxOjF|IN88US=> NV\GbWg1W0GQR2LFVi=>
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NCI-H2107 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{DyUmlEPTB;Mj64N|cyOSEQvF2= MUTTRW5IWkWU
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HD-MY-Z NHrVelJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn7nTWM2OD12Nj60OlEzKM7:TR?= MWDTRW5IWkWU
L-363 NXnSR|VCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2S0ZmlEPTB;NE[uPFgyKM7:TR?= NUXRNllrW0GQR2LFVi=>
TE-6 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXjze|JxUUN3ME20PE41PDZizszN MkDqV2FPT1KHUh?=
NCI-H345 NU\KeIs3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYjJR|UxRTR6LkS2PEDPxE1? M4H4d3NCVkeURWK=
TE-5 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIizNphKSzVyPUS5MlcyOThizszN NIrpWZNUSU6JUlXS

... 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
In vivo VX-680 gives rise to a marked decrease in tumor size in a human AML (HL-60) xenograft model. In mude mice treateed with VX-680 at 75 mg/kg, twice a day intraperitoneally (b.i.d. i.p.) for 13 days, mean tumor volumes are reduced by 98%. Tumor growth decrease is dose dependent and significant at a dose of 12.5 mg/kg b.i.d. VX-680 is well tolerated, with a small decrease in body weight observed only at the highest dose. VX-680 also triggers tumor regresson in pancreatic and colon xenograft models. VX-680 also displays potent antitumor activity when infused i.v. in mude rats bearing established HCT116 tumors. A higher dose of VX-680 (2 mg/kg/h) improves efficacy with a 56% decrease in mean tumor volume. [1]

Protocol

Kinase Assay:

[3]

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Kinase inhibition assays:

The consumption of ATP is coupled via the pyruvate kinase/lactic dehydrogenase enzyme pair to the oxidation of NADH, which can be monitored through the decrease in absorption at 340 nm. Reactions contains 100 mM Tris (pH 8), 10 mM MgCl2, 2.2 mM ATP, 1 mM phosphoenolpyruvate, 0.6 mg/mL NADH, 75 units/mL pyruvate kinase, 105 units/mL lactate dehydrogenase, and 0.5 mM substrate peptide (sequence: EAIYAAPFAKKK). Reactions (75 μL) are started by adding sufficient kinase to bring the reactions to 30 nM kinase concentration and the decrease in absorbance is monitored over 30 minutes at 30°C in a microtiter plate spectrophotometer. Inhibitory constants are obtained through addition of 3.75 μL VX-680 in 100% DMSO or DMSO alone. Ki values are calculated as follows, K i = IC50 / (1 + [S]/Kd), where [S] = [ATP] = 2.2 mM, and Kd (of ATP to Abl) = 70 μM. These values are calculated assuming a Kd (ATP) of 70 μM for wild type and H396P Abl kinase domain.
Cell Research:

[2]

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  • Cell lines: CAL-62 cells
  • Concentrations: 5-500 nM
  • Incubation Time: 4 days
  • Method:

    The CAL-62 cells are cultured in the absence (dimethyl sulfoxide, DMSO) or the presence of 500  nM VX-680 for different periods of time (1-5 days). The dose-dependent effects of VX-680 on cell proliferation are evaluated by treating the different ATC cells for 4 days with different concentrations of the Aurora inhibitor (5–500  nM). The cells are pulse labeled with 30  mM BrdU for 2  hours before the end of the incubation time. The BrdU incorporation is analyzed by means of a colorimetric immunoassay using the cell proliferation ELISA kit. The results from VX-680-treated cells are compared with those observed in control cells and expressed as a fold of variation versus control.


    (Only for Reference)
Animal Research:

[1]

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  • Animal Models: Female athymic NCr-nu mice bearing HL-60 leukemia cells
  • Dosages: 50 mg/kg, 75 mg/kg
  • Administration: Administered via i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 93 mg/mL (200.17 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
5% DMSO+30% PEG 300+2% Tween 80+ddH2O
For best results, use promptly after mixing.
15mg/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 464.59
Formula

C23H28N8OS

CAS No. 639089-54-6
Storage powder
in solvent
Synonyms N/A
Smiles CC1=CC(=NN1)NC2=CC(=NC(=N2)SC3=CC=C(C=C3)NC(=O)C4CC4)N5CCN(CC5)C

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
CalculateReset

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)

  • Mass
    Concentration
    Volume
    Molecular Weight

*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 )

  • C1
    V1
    C2
    V2

* 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

  • 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):
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.

Molarity Calculator

Mass Concentration Volume Molecular Weight

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.

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Aurora Kinase Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID