Tozasertib

Catalog No.S1048 Synonyms: VX-680, MK-0457

For research use only.

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.

Tozasertib  Chemical Structure

CAS No. 639089-54-6

Selleck's Tozasertib has been cited by 120 publications

Purity & Quality Control

Choose Selective Aurora Kinase Inhibitors

Other Aurora Kinase Products

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 M4jRcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVLJR|UxRTBwMECzN|gh|ryP NYrEb4ZMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
RS4-11 NVzOVZQ{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV3JR|UxRTBwMEC0NFQh|ryP NEPMNng9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
MFH-ino M1nBNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEXaO|JKSzVyPUCuNFA6QSEQvF2= MljhQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
NTERA-S-cl-D1 NGX5b2dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkLXTWM2OD1yLkCxOFM1KM7:TR?= MorWQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
697 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVTJR|UxRTBwMEK0O|Eh|ryP M17EbVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
NALM-6 NF;VWGJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoHyTWM2OD1yLkCyOVUzKM7:TR?= NHjsTlI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
ES8 NHT6V3BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlnITWM2OD1yLkC0OlE{KM7:TR?= NX3kNIVYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
HUTU-80 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWDISZozUUN3ME2wMlA2Ojl7IN88US=> NWnlXXZrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
MV-4-11 NIDMV5NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXzzOVhRUUN3ME2wMlA4Pzh{IN88US=> M1Kxd|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
MONO-MAC-6 NWGzXG5{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXfJR|UxRTBwMEe4O|kh|ryP NYi2VoozRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
LC-2-ad MlrtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUX6W2VDUUN3ME2wMlA5Pzh7IN88US=> NYLBfXZHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
BL-41 MnvDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHLJTJlKSzVyPUCuNVA1PDVizszN NUjNXos5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
A4-Fuk NEnlNlVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFHDS2JKSzVyPUCuNVE2PjNizszN MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O|I5PzhxJ{7TRW5IWkWUPD;hQi=>
SW954 NVe1cmQyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIntOmZKSzVyPUCuNVIzOjlizszN MoHRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
BV-173 NEPweXJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4LyXGlEPTB;MD6xNlY1OSEQvF2= M17nZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
TE-11 MnnpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUDJR|UxRTBwMUS5PFIh|ryP Mmf5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
SK-UT-1 MnvoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoPBTWM2OD1yLkG1PVY2KM7:TR?= NEDKUnk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
SIG-M5 NIWzT4lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUHncZpKUUN3ME2wMlE3PzB5IN88US=> M1vZZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
OCUB-M MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUTiZm1TUUN3ME2wMlE3QTh|IN88US=> MoW0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
K052 NX3lXFZzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXrvcFFnUUN3ME2wMlE6PDhizszN NEjYdIU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
VA-ES-BJ M3PNNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXjjXmliUUN3ME2wMlIxODh4IN88US=> NGDtfW49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
SW982 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHnXN3RKSzVyPUCuNlE{QCEQvF2= NVP1PZZoRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
LB647-SCLC NXLVcm9GT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYi0UFVjUUN3ME2wMlIyPTJ|IN88US=> M2DKSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
PSN1 M3\3VWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVnRc|FwUUN3ME2wMlIzODJ4IN88US=> NWDlNnpyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
BB30-HNC M{fRW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4j1TGlEPTB;MD6yNlU6OSEQvF2= MnrjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
ST486 NIHjfJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MW\JR|UxRTBwMkOwPFch|ryP M3f2bFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
MOLT-4 NVvBcJVIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEnQfG5KSzVyPUCuNlM{OzdizszN NHW2TYs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
EW-16 NYjPWlZrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2P1NWlEPTB;MD6yN|c3QCEQvF2= Mk\VQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
KS-1 MoDsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWPHeWt6UUN3ME2wMlI{Pzh3IN88US=> NF\Xd4U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
SR NH[1OXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVv0W|R6UUN3ME2wMlI1PTZ2IN88US=> MkO2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
KM12 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1\Sb2lEPTB;MD6yOlM3KM7:TR?= NELMeJM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
EM-2 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXjJR|UxRTBwMk[2OFEh|ryP MnHsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
MEG-01 NXzlN44xT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoD0TWM2OD1yLkK3PFQ6KM7:TR?= M4TCZ|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
NB13 Ml;2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{TEfWlEPTB;MD6yO|k5PCEQvF2= NVnHXolERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
RKO NV\ReFRZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NETYPHBKSzVyPUCuN|A5OTNizszN MoO5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
CESS MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2PVb2lEPTB;MD6zNVMzQCEQvF2= MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O|I5PzhxJ{7TRW5IWkWUPD;hQi=>
EoL-1-cell MmmwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnrmTWM2OD1yLkOzOFU6KM7:TR?= NIfqPJA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
DOHH-2 NV;aVpg1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVXocpFTUUN3ME2wMlM{PzhzIN88US=> M4TTO|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
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LAMA-84 M4fvTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWTzdIV2UUN3ME2wMlM2OTd6IN88US=> NFXicGY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
IMR-5 NIqwOpdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHLZeJhKSzVyPUCuN|U2PCEQvF2= NFXZSlY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK|5USU6JUlXSQE9iRg>?
KARPAS-422 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWDJR|UxRTBwM{eyO|Ih|ryP M1T2Z|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
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A549 M3\hOWFvfGmycn;sbYZmemG2aY\lJIF{e2G7 NHjFe5Y1QCCqcoO= NEP3WYNCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFG1OFkh[2WubIOgZYZ1\XJiNEigbJJ{KGK7IF3UWEBie3OjeTygS2k2OD1|NT64{txO MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODVyMkGxOUc,OzB3MEKxNVU9N2F-
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Assay
Methods Test Index PMID
Western blot DLK / p-MKK7 / MKK7 / p-JNK / JNK ; p-AURKA / AURKA / Survivin ; YAP ; p-AKT / p-GSK3β / Cleaved caspase-3 / Cleaved PARP 23431148 28218735 31160567 21600017
Immunofluorescence α-tubulin / Aurora-A 21600017
Growth inhibition assay Cell viability 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 (from reference)

Kinase Assay:

[3]

  • 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]

  • 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.

Animal Research:

[1]

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

Solubility (25°C)

In vitro

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.

3.75 mg/mL

Chemical Information

Molecular Weight 464.59
Formula

C23H28N8OS

CAS No. 639089-54-6
Storage 3 years -20°C powder
2 years -80°C in solvent
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)

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
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

(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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