Tozasertib (VX-680, MK-0457)

Catalog No.S1048

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

Molecular Weight(MW): 464.59

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. Phase 2.

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Cited by 36 Publications

16 Customer Reviews

  • (G) Nocodazole-arrested HeLa cells were treated with VX-680 and MG132 and stained for CENP-E (Green), pT422 (Red) and DNA (Blue). (H) pT422 fluorescence intensity was normalized to the total CENP-E fluorescence. Plots show the mean of > 15 cells per condition from two independent experiments.

    Cell 2010 142, 444–455. Tozasertib (VX-680, MK-0457) purchased from Selleck.

    Senescence induction upon PKCι depletion combined with aurora kinase inhibition. ( a) MCF7 cells were transfected as above to deplete PKCι . Two days after transfection, cells were treated for the indicated time period with 400 n M VX-680. Medium with VX-680 was then removed and fresh medium was added. Cells were stained for SA-b -gal activity 5 days after the start of transfection.* indicates a P value <0.05. ( b) MCF7 cells were treated as above. Five days after transfection, cells were fixed and assessed for the presence of gH2AX foci by immunofluorescence microscopy. (c, d) MCF7 cells were treated with dimethyl sulfoxide (DMSO) control or 400 n M VX-680 for the indicated time periods. Total cell lysates were then analyzed by western blotting for levels of p21 and GAPDH (as loading control). A representative blot is shown in panel c. Quantitation of changes in p21 levels (normalized to vehicle-treated controls) is shown in panel d. The data shown are the means ±s.e. of three independent experiments.

    Oncogene 2012 31, 3584-96. Tozasertib (VX-680, MK-0457) purchased from Selleck.

  • Senescence induction upon PKCι depletion combined with aurora kinase inhibition in glioblastoma cells. (a, b) U87MG cells were transfected as above to deplete PKCι. Two days after transfection, cells were treated for 72 ( a)or24h (b) with 400 nM VX-680. Medium with VX-680 was then removed and fresh medium was added. Cells were stained for SA-b-gal activity 5 days after the start of transfection. * indicates a P value <0.05. (c) U87MG cells were treated as described in panel a above. Five days after transfection, cells were fixed and assessed for the presence of gH2AX foci by immunofluorescence microscopy. (d) U87MG cells were treated with the dimethyl sulfoxide (DMSO) control or 400 n M VX-680 for the indicated time periods. Total cell lysates were then analyzed by western blotting for levels of p21. The bar graph shows quantitation of p21 levels (normalized to vehicle-treated controls) from three independent experiments. A representative blot is also shown, with lanes aligned to correspond to the labels on the graph.

    Oncogene 2012 31, 3584-96. Tozasertib (VX-680, MK-0457) purchased from Selleck.

     

    Aurora-A inhibitors severely impair neuronal migration. Migration of granular neurons after treatment of Aurora-A inhibitors was examined. a, Western blotting analysis of proteins or phosphorylated proteins. Aurora-A and NDEL1 displayed similar expression levels, whereas phosphorylated Aurora-A and NDEL1 proteins were decreased during treatment with Aurora-A inhibitors. Relative intensities of the bands of Western blotting are displayed at the bottom.

    J Neurosci 2012 32, 11050-11066. Tozasertib (VX-680, MK-0457) purchased from Selleck.

  • B, BLQ1 and UCSF02 cells were treated with increasing concentrations of VX-680 for 48 hours. The percentage of apoptotic cells was determined by fluorescence-activated cell sorting analysis. C, BLQ1 cells were treated with 1 μmol/L VX-680 and cell cycle distribution was determined by flow cytometry at time points of 24 and 48 hours.

    Mol Cancer Ther 2010 9, 1318–1327. Tozasertib (VX-680, MK-0457) purchased from Selleck.

    VX-680 eliminates Bcr/Abl kinase activities. BLQ1 (T315I mutation) and TXL2 (no mutation) cells were treated with the indicated concentrations of VX-680 with or without 100 nmol/L dasatinib for 24 hours. Western blot analysis was done on total lysates with the antibodies indicated to the left. Blots were stripped and reprobed with Bcr (N-20), Src, and GAPDH antibodies as loading controls.

    Mol Cancer Ther 2010 9, 1318–1327. Tozasertib (VX-680, MK-0457) purchased from Selleck.

  • Responses of human ALL cells to short-term VX-680 treatment. A, BLQ1 cells were treated with 1 μmol/L VX-680 for 3 days. After 3 days, the drug was removed from the medium and cells were cultured without VX-680. During this period (days 3-21) without drug, viability (top left), cell numbers (bottom left), and cell cycle distribution (right) of BLQ1 cells were assessed. B, BLQ1 and BLQ1-VX-Tx cells were cytospun onto glass slides and fixed, dried, and stained with Wright-Giemsa on day 21. All images are at ×63 magnification. C, BLQ1 and BLQ1-VX-Tx cells were treated with 1.5 μmol/L VX-680 or 5 nmol/L vincristine for 72 hours. Cell viability was measured by trypan blue exclusion. *, P < 0.05, vincristine-treated BLQ1 compared with vincristine-treated BLQ1-VX-Tx.

    Mol Cancer Ther 2010 9, 1318–1327. Tozasertib (VX-680, MK-0457) purchased from Selleck.

    VX-680 and dasatinib synergize to induce cytotoxic activity in wild-type Bcr/Abl-positive human ALL cells. A, TXL2 and UCSF02 cells were exposed to 1 μmol/L VX-680 with or without 100 nmol/L dasatinib for 24 to 72 hours as indicated, after which the percentage of viable cells was determined by trypan blue exclusion. B, TXL2 cells were treated with or without VX-680 and dasatinib for 48 hours in triplicate. **, P < 0.001, VX-680 and dasatinib cotreated TXL2 compared with VX-680-treated or dasatinib alone-treated TXL2 cells. Apoptotic cells were defined by flow cytometry as Annexin V and propidium iodide (PI) double-positive cells. C, TXL2 cells were exposed to VX-680 and/or dasatinib and cell cycle distribution was assessed by flow cytometry.

    Mol Cancer Ther 2010 9, 1318–1327. Tozasertib (VX-680, MK-0457) purchased from Selleck.

  • MTT assay reveals a dose-dependent decrease in cell viability in mouse derived brainstem glioma cells treated with VX-680 ( P < 0.001) after 72 h of treatment. The error bars represent the standard deviation. Propidium iodide based cell sorting of mouse derived brainstem glioma cells after 72 h treatment with 5 μM reversine or 100 nM VX-680 respectively reveals increased cell populations with 4N and 8N DNA content as compared to vehicle control.

    Brain Pathol 2012 23, 244-53. Tozasertib (VX-680, MK-0457) purchased from Selleck.

    Treatment of mouse derived brainstem glioma cells for 72 h with 5 μM reversine or 100 nM VX-680 increases cell size compared with vehicle-treated control and leads to irregular-shaped nuclei and micronuclei (F–H). Images F–H represent immunofluorescent staining for GFAP (green) with DAPI counter-stain (blue) and were taken at 400 ×magnification.

    Brain Pathol 2012 23, 244-53. Tozasertib (VX-680, MK-0457) purchased from Selleck.

  • C, E: Expression of Aur-A and phosphorylated histone H3 in TPC-1 cells after VX-680 treatment. D, F: Expression of phosphorylated histone H3 in PTC tumor tissues after VX-680 treatment.

    Biochem Biophys Res Commun, 2016, 473(1):212-8. Tozasertib (VX-680, MK-0457) purchased from Selleck.

    Apoptosis induction in HB cells treated with a combination of VX-680. HUH6 (a) and HepT1 ( b ) were incubated with VX-680 (6 and 12.5 μM). Caspase-3 activation was detected with the NucView- 488 substrate 24 h later. Green fluorescent cells denote apoptotic cells.Scale bar represents 50 μm.

    Pediatr Surg Int 2012 28, 579-89. Tozasertib (VX-680, MK-0457) purchased from Selleck.

  • Morphological changes and histone H3 phosphorylation of HB cells treated with a combination of VX-680 and SAHA. HUH6 and HepT1 were incubated with VX-680 (6 μM) and SAHA (0.5 μM). Nuclei diameter (a) and cell diameter (b) were determined 72 h later by DAPI staining and microscopy. Data represent mean±SD of the diameters from 20 cells in each experiment. (* Two-way ANOVA, Bonferroni test, p \0.05). c Western blot analysis on HUH6 and HepT1 cells were carried out with an anti-phospho-Histone H3 (Ser 10) antibody (p-H3) 24 h after incubation with VX-680 (10 μM), SAHA (0.2 μM) or a combination of both. Controls were left untreated. Western blot analysis showed a decrease in p–H3 after treatment with VX-680 ( lane 2 ) relative to controls ( lane 1 ) and an increase when SAHA was added ( lane 3 ). For the combination of VX-680 and SAHA (lane 4 ) no p-H3 was detected.

    Pediatr Surg Int 2012 28, 579-89. Tozasertib (VX-680, MK-0457) purchased from Selleck.

    ENMD-2076 has benn tested it on two different neurobiastoma cell lines(SK-N-BE(2) and CHP-134),being calculated the IC50 by a WST-1(Roche) proliferation assay, as shown in the table below. Its in vitro activity is in the micromolar range and has a comparable effect on both lines.VX-680 was used as standard, and it proved more potent on CHP-134 cells.

    Dr. Antonino Maria Sparta ,University of Trento. Tozasertib (VX-680, MK-0457) purchased from Selleck.

  • SDS-PAGE of CHP-134 cells extracts after 24 h exposure to the indicated drug and concentration. N-myc levels were evaluated and compared to beta actin used as house-keeping protein. Aurora A blockade seems to diminish N-myc expression or stability.

    Dr. Antonino Maria Sparta ,University of Trento. Tozasertib (VX-680, MK-0457) purchased from Selleck.

    Western blot analysis of Histone and Aurora kinase. 0-10μM MK0457 was added.

    Dr. Zhang of Tianjin Medical University. Tozasertib (VX-680, MK-0457) purchased from Selleck.

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. 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 NVza[VNST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIjrO4lKSzVyPUCuNFA{OzhizszN MVrTRW5IWkWU
RS4-11 NIXBN4xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVfC[JVwUUN3ME2wMlAxPDB2IN88US=> NHzOTHlUSU6JUlXS
MFH-ino MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{DGeWlEPTB;MD6wNFk6KM7:TR?= MWnTRW5IWkWU
NTERA-S-cl-D1 NYLB[2lNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M37lXmlEPTB;MD6wNVQ{PCEQvF2= MVPTRW5IWkWU
697 NHzpTopIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlP4TWM2OD1yLkCyOFcyKM7:TR?= NV3k[XN3W0GQR2LFVi=>
NALM-6 MlXhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIjtdlVKSzVyPUCuNFI2PTJizszN NF7HRmhUSU6JUlXS
ES8 MmfSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkTpTWM2OD1yLkC0OlE{KM7:TR?= MWnTRW5IWkWU
HUTU-80 NWjZOWFCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFXBOGNKSzVyPUCuNFUzQTlizszN Mo\vV2FPT1KHUh?=
MV-4-11 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MluxTWM2OD1yLkC3O|gzKM7:TR?= NEH5T45USU6JUlXS
MONO-MAC-6 NGm1XFhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFLz[2ZKSzVyPUCuNFc5PzlizszN M1PzcnNCVkeURWK=
LC-2-ad MkG3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYHScpd2UUN3ME2wMlA5Pzh7IN88US=> M3ezbXNCVkeURWK=
BL-41 NIPpTHFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIS5XoFKSzVyPUCuNVA1PDVizszN MnTGV2FPT1KHUh?=
A4-Fuk NYXBe2E3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2P6SWlEPTB;MD6xNVU3OyEQvF2= MorIV2FPT1KHUh?=
SW954 MmTWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4nLUWlEPTB;MD6xNlIzQSEQvF2= NWXxdpF{W0GQR2LFVi=>
BV-173 NVj4ZZE4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmLLTWM2OD1yLkGyOlQyKM7:TR?= M1PJVnNCVkeURWK=
TE-11 M3L6Omdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkizTWM2OD1yLkG0PVgzKM7:TR?= NFjPS|NUSU6JUlXS
SK-UT-1 MoHsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3nFS2lEPTB;MD6xOVk3PSEQvF2= NV;oOZVzW0GQR2LFVi=>
SIG-M5 NWTBUpp6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3vsR2lEPTB;MD6xOlcxPyEQvF2= MWnTRW5IWkWU
OCUB-M MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M17iO2lEPTB;MD6xOlk5OyEQvF2= M3jFfXNCVkeURWK=
K052 NU\wdId2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVjJR|UxRTBwMUm0PEDPxE1? MV7TRW5IWkWU
VA-ES-BJ NFGzbFZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEf3fWNKSzVyPUCuNlAxQDZizszN M4LlWHNCVkeURWK=
SW982 MoPMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGXJUG1KSzVyPUCuNlE{QCEQvF2= NHfzb4RUSU6JUlXS
LB647-SCLC M3LjTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4TzWmlEPTB;MD6yNVUzOyEQvF2= MXLTRW5IWkWU
PSN1 NUDG[oE4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGe2blFKSzVyPUCuNlIxOjZizszN M{\Wc3NCVkeURWK=
BB30-HNC MmK3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoHYTWM2OD1yLkKyOVkyKM7:TR?= NX3KTWFIW0GQR2LFVi=>
ST486 MlHXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGHpPXlKSzVyPUCuNlMxQDdizszN NGLvS41USU6JUlXS
MOLT-4 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoLQTWM2OD1yLkKzN|M4KM7:TR?= MnLrV2FPT1KHUh?=
EW-16 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV7JR|UxRTBwMkO3Olgh|ryP NWGxbGxVW0GQR2LFVi=>
KS-1 NF7wemRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHL0VYdKSzVyPUCuNlM4QDVizszN M1\RbXNCVkeURWK=
SR NHTWT49Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{fKbmlEPTB;MD6yOFU3PCEQvF2= M2jCOXNCVkeURWK=
KM12 MoryS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4D6emlEPTB;MD6yOlM3KM7:TR?= MUDTRW5IWkWU
EM-2 NF60[HZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFvqZVBKSzVyPUCuNlY3PDFizszN MULTRW5IWkWU
MEG-01 MonWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoT5TWM2OD1yLkK3PFQ6KM7:TR?= MojkV2FPT1KHUh?=
NB13 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1PtZmlEPTB;MD6yO|k5PCEQvF2= NIjEbIZUSU6JUlXS
RKO MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1zVU2lEPTB;MD6zNFgyOyEQvF2= NITZSVdUSU6JUlXS
CESS Ml\TS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUfJR|UxRTBwM{GzNlgh|ryP NELaSW5USU6JUlXS
EoL-1-cell Moi4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlnQTWM2OD1yLkOzOFU6KM7:TR?= NFXOVWpUSU6JUlXS
DOHH-2 NHvw[WZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkXKTWM2OD1yLkOzO|gyKM7:TR?= MmjnV2FPT1KHUh?=
A388 MkPMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIjlNmtKSzVyPUCuN|QxQDZizszN NIL5VIdUSU6JUlXS
LAMA-84 MlvkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkL1TWM2OD1yLkO1NVc5KM7:TR?= MVnTRW5IWkWU
IMR-5 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHnzOVNKSzVyPUCuN|U2PCEQvF2= MkL4V2FPT1KHUh?=
KARPAS-422 NUHNVllkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2LUV2lEPTB;MD6zO|I4OiEQvF2= MoHMV2FPT1KHUh?=
MRK-nu-1 MljLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkfvTWM2OD1yLkO4NVMh|ryP MYDTRW5IWkWU
BL-70 M4fzcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MofuTWM2OD1yLkO4PVc1KM7:TR?= NULKcnE3W0GQR2LFVi=>
LXF-289 M{mzTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH\tWIVKSzVyPUCuOFA1ODZizszN M4myfXNCVkeURWK=
RL95-2 Mm\JS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGLYUnJKSzVyPUCuOFA2PjdizszN MnTkV2FPT1KHUh?=
QIMR-WIL NWPrS5ZwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1vMWWlEPTB;MD60NlY4PiEQvF2= NIPD[3NUSU6JUlXS
K-562 MlLkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NI\MZlFKSzVyPUCuOFM1PzJizszN Mle1V2FPT1KHUh?=
NCI-H510A M1;OPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmT2TWM2OD1yLkSzPFI{KM7:TR?= Mk\kV2FPT1KHUh?=
NCI-H524 NIW4O4VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFLuT4tKSzVyPUCuOVEyPDdizszN NVO2dZUzW0GQR2LFVi=>
KE-37 NV3BNms3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH7wcnpKSzVyPUCuOVIyODJizszN Mn\UV2FPT1KHUh?=
KP-N-YS M2nFSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH\xeG1KSzVyPUCuOVQ{QTJizszN MoP6V2FPT1KHUh?=
LS-411N MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkXSTWM2OD1yLkW3O|UzKM7:TR?= NHPPUYNUSU6JUlXS
CTV-1 NU\ZVmtHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnzjTWM2OD1yLkW4O|c{KM7:TR?= Mm\DV2FPT1KHUh?=
NCI-SNU-16 Ml;0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MojNTWM2OD1yLk[zOVcyKM7:TR?= NWXGO2ZMW0GQR2LFVi=>
HT-144 NIS5U5lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NG\lSG1KSzVyPUCuOlM4QThizszN MkHMV2FPT1KHUh?=
NCI-H187 NV\4e2g6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFT1Z3lKSzVyPUCuOlQyOyEQvF2= MUPTRW5IWkWU
OCI-AML2 M2DIPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1HNV2lEPTB;MD62OFQxOyEQvF2= MVXTRW5IWkWU
CCRF-CEM Mn3nS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{nIb2lEPTB;MD62OVM1PiEQvF2= MnLSV2FPT1KHUh?=
ONS-76 NULHV4M6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVXJR|UxRTBwNk[0OVgh|ryP MYDTRW5IWkWU
IST-SL2 MoLTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYLJR|UxRTBwN{G5PFIh|ryP M1PDOnNCVkeURWK=
NB6 NWq0TGxRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUPmRlBzUUN3ME2wMlc4OjV2IN88US=> NHLM[XFUSU6JUlXS
SK-PN-DW NYHVWo95T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIjO[GNKSzVyPUCuO|kyPCEQvF2= M{fN[3NCVkeURWK=
HCC1599 M2fESGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV\XVIJJUUN3ME2wMlgxQDd2IN88US=> M1zwdnNCVkeURWK=
MC116 NYntR5pNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mnf4TWM2OD1yLki1NFEyKM7:TR?= Ml\xV2FPT1KHUh?=
TE-15 M1\rOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2rwNGlEPTB;MD64OVA6QCEQvF2= NU\FSmdDW0GQR2LFVi=>
HOP-62 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1zUR2lEPTB;MD64OlMzQSEQvF2= NUC0OpRjW0GQR2LFVi=>
TGBC24TKB NYr1UIJ[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH\hNpVKSzVyPUCuPFY{QDVizszN NYXSNVBoW0GQR2LFVi=>
HCE-4 MofOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUL3V5ZoUUN3ME2wMlg5ODZ|IN88US=> M2SzPXNCVkeURWK=
ALL-PO MoL5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnPRTWM2OD1yLki4NVc2KM7:TR?= NVLPPHRXW0GQR2LFVi=>
KGN M4P6bmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWXMN4luUUN3ME2wMlg6QTl3IN88US=> NEDxUmdUSU6JUlXS
ML-2 NWS4eotoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVjTZ3dGUUN3ME2wMlkxOjV7IN88US=> Mo\4V2FPT1KHUh?=
ES4 NXHv[INJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MljmTWM2OD1yLkmxNVI5KM7:TR?= NEmxXGhUSU6JUlXS
SF126 M1TBPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn3wTWM2OD1yLkm0PFE6KM7:TR?= Mn2zV2FPT1KHUh?=
SK-N-DZ MlfLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXHJR|UxRTBwOU[xPFkh|ryP MX;TRW5IWkWU
HCC1187 Mn3BS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MW\JR|UxRTFwMEC1NFUh|ryP M1O1dnNCVkeURWK=
DU-4475 MoP1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX\wR2tGUUN3ME2xMlAyPzV4IN88US=> M2fxO3NCVkeURWK=
NKM-1 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUjSbVJ4UUN3ME2xMlAzPzd3IN88US=> NUW0bottW0GQR2LFVi=>
HL-60 NUXFfGQyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIi5eGVKSzVyPUGuNFY2PzRizszN NI[1U2JUSU6JUlXS
SBC-1 NWSybZdTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4D5emlEPTB;MT6xNlU1OiEQvF2= MYDTRW5IWkWU
TE-10 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVXJR|UxRTFwMUK5OFYh|ryP M1PtOnNCVkeURWK=
ETK-1 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVzJR|UxRTFwMUO2NVMh|ryP NFnFOJpUSU6JUlXS
HAL-01 NYO0VYttT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmPsTWM2OD1zLkG2O|A6KM7:TR?= M4jUOXNCVkeURWK=
BB65-RCC MkHkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVPwbJV3UUN3ME2xMlE5ODB3IN88US=> MVvTRW5IWkWU
EW-1 M1vX[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGTwN|hKSzVyPUGuNVg2PjJizszN NIHKeWpUSU6JUlXS
SK-NEP-1 M3j1SWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFvOboVKSzVyPUGuNlEyOTFizszN Mn3SV2FPT1KHUh?=
SK-LMS-1 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWfJR|UxRTFwMkKyNVIh|ryP M4f1V3NCVkeURWK=
DEL Mlv1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NILZVW1KSzVyPUGuNlU3PDNizszN MX7TRW5IWkWU
GT3TKB NGGyV2FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkXBTWM2OD1zLkK4NFU4KM7:TR?= MX7TRW5IWkWU
MOLT-16 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEnrUllKSzVyPUGuN|U1ODVizszN M{[ydnNCVkeURWK=
CMK M{DYRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWL0bHZUUUN3ME2xMlQzOTF5IN88US=> MYXTRW5IWkWU
NB5 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUXJR|UxRTFwNkSyNlkh|ryP MWrTRW5IWkWU
NCI-H1963 NHr2XFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MknVTWM2OD1zLkewOVg{KM7:TR?= MkXjV2FPT1KHUh?=
KURAMOCHI M{jvSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mki2TWM2OD1zLke4PVEyKM7:TR?= NFzZNVFUSU6JUlXS
TE-8 NHeyR|FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEW0VINKSzVyPUGuPFA{PjhizszN MV;TRW5IWkWU
NCI-H1304 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWXJR|UxRTFwOEOwO|Mh|ryP MWXTRW5IWkWU
A101D NVj1ZlBYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIT6dnpKSzVyPUGuPFc{QTVizszN NVPlW2U5W0GQR2LFVi=>
SCLC-21H NXmzTppIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnLkTWM2OD1zLkm3NFU4KM7:TR?= MWPTRW5IWkWU
GB-1 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGrINZJKSzVyPUKuNFE3PDdizszN NV;D[I1tW0GQR2LFVi=>
KARPAS-45 M33TfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVvJR|UxRTJwMEK2OVQh|ryP M3vpPHNCVkeURWK=
ATN-1 NHfNe5lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYHJR|UxRTJwMEK4OVgh|ryP MnrMV2FPT1KHUh?=
NCI-H720 MoC1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml:wTWM2OD1{LkC2NlQ1KM7:TR?= M1LBeHNCVkeURWK=
RPMI-6666 MlvZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXPJR|UxRTJwMU[yNFch|ryP MWXTRW5IWkWU
NB17 M{\ncGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkjnTWM2OD1{LkK5Nlch|ryP NXjwdFNtW0GQR2LFVi=>
IST-SL1 M3;oe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mmj0TWM2OD1{LkK5O|Y2KM7:TR?= M{nEdHNCVkeURWK=
SH-4 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF;CN21KSzVyPUKuN|I1PjlizszN NUDMd4NXW0GQR2LFVi=>
K5 NEC5PJdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1\OXmlEPTB;Mj60NFMyQSEQvF2= M4rs[XNCVkeURWK=
OVCAR-4 M2Xt[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmXvTWM2OD1{LkS2NVMh|ryP MlnyV2FPT1KHUh?=
ACN NIWzNVZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVHhfpZRUUN3ME2yMlUxOjF|IN88US=> M2G3UXNCVkeURWK=
TGW MmThS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NE\RWHRKSzVyPUKuOlU5OzJizszN NF;QbIJUSU6JUlXS
NCI-H2107 NUXFdYdST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWnQOHliUUN3ME2yMlg{PzFzIN88US=> NGTsUVJUSU6JUlXS
NCI-H82 NWj0eFB{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV33fmpJUUN3ME2yMlg{QDN6IN88US=> MXTTRW5IWkWU
SK-N-FI NX7hW493T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYrTeplTUUN3ME2yMlg3QDZ6IN88US=> MUXTRW5IWkWU
LB1047-RCC M4\LSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGLYSGFKSzVyPUKuPFgyOjZizszN MXfTRW5IWkWU
LU-134-A NGm5RZVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWj2e3lpUUN3ME2yMlg6OjZizszN NWK5RpNZW0GQR2LFVi=>
NCI-H209 MljCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnfyTWM2OD1{LkmxNlU{KM7:TR?= MWXTRW5IWkWU
NOMO-1 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUnqbHlGUUN3ME2zMlAzOjd2IN88US=> NVm5[|g6W0GQR2LFVi=>
RH-1 NVzaZpA3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoW2TWM2OD1|LkG3NlkyKM7:TR?= NFvIS2hUSU6JUlXS
LOUCY M{DD[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3rQfGlEPTB;Mz6xPFY6OyEQvF2= MUHTRW5IWkWU
TE-9 M17FZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2PEOWlEPTB;Mz6yOlc{PiEQvF2= NHXqbpRUSU6JUlXS
PF-382 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVTURmpEUUN3ME2zMlM2Pzd6IN88US=> NXnRW4dFW0GQR2LFVi=>
RPMI-8402 NWXDT29ET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NI[xN|JKSzVyPUOuOVg3ODNizszN NYC1clltW0GQR2LFVi=>
HEL M{HlbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoPITWM2OD1|Lk[zNkDPxE1? MXjTRW5IWkWU
NOS-1 MonuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVHJR|UxRTNwOES3OVQh|ryP NEizTVZUSU6JUlXS
ES1 NGjtNXVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYLOOZBEUUN3ME2zMlkzOjl|IN88US=> M{HrXXNCVkeURWK=
NCI-H2171 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn32TWM2OD1|LkmyOFI{KM7:TR?= M4jpc3NCVkeURWK=
NCI-H747 NX7X[JpNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3vDSGlEPTB;Mz65OFIzOSEQvF2= MUHTRW5IWkWU
MHH-NB-11 M2TmWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NE\zeZZKSzVyPUOuPVU{OTJizszN MYDTRW5IWkWU
MZ1-PC NUjBT5c2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWrNSVA5UUN3ME2zMlk6OjRizszN MXnTRW5IWkWU
MMAC-SF MmfRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1PrcGlEPTB;ND6wNlQ3PyEQvF2= NWrDRWtNW0GQR2LFVi=>
NMC-G1 MlPGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWL5fpNRUUN3ME20MlIzPzJ|IN88US=> NEO3d4dUSU6JUlXS
SW872 NGrOfpFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF30WXRKSzVyPUSuN|Q{PCEQvF2= Mkj5V2FPT1KHUh?=
TE-12 MlLZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{fEdWlEPTB;ND61OlM6PCEQvF2= NGHpRoZUSU6JUlXS
LU-139 NGnQT|hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4m4U2lEPTB;ND62NVg{PSEQvF2= M3PIb3NCVkeURWK=
HC-1 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGL5[JZKSzVyPUSuOlk1QTRizszN NXLzXZVwW0GQR2LFVi=>
COR-L279 MmPUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M37LW2lEPTB;ND63OVg6OSEQvF2= M2PZU3NCVkeURWK=
SF268 NWjDTI5yT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX;qU4JzUUN3ME20Mlc6QTF4IN88US=> MmjFV2FPT1KHUh?=
MC-CAR NFXqWJhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF\SVXhKSzVyPUWuNFY4PTdizszN MYrTRW5IWkWU
TK10 NXnZ[o9lT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlfJTWM2OD13LkO1OFY6KM7:TR?= Mn36V2FPT1KHUh?=
TE-1 NXr5[plLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkTQTWM2OD13LkS5NFA1KM7:TR?= NHLGPIhUSU6JUlXS
NCI-H2126 NULBXlF1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUXhdY9iUUN3ME21MlY1PTd2IN88US=> MV\TRW5IWkWU
Daudi M1TJVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUjJR|UxRTVwNkmxNkDPxE1? MUjTRW5IWkWU
NCI-H1648 MmPMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlLyTWM2OD13LkixOFU1KM7:TR?= M2jYS3NCVkeURWK=
OS-RC-2 NUS3dZdlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUfJR|UxRTVwOUi1PVch|ryP MYXTRW5IWkWU
DJM-1 MlH3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXnCdot5UUN3ME22MlM1PjZ4IN88US=> M1e1NXNCVkeURWK=
LS-1034 MnnWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1H4bmlEPTB;Nj63OVY3KM7:TR?= NH:xUlVUSU6JUlXS
NCI-H1581 M4jCb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnPQTWM2OD14Lke4OFA2KM7:TR?= NXXBXJFxW0GQR2LFVi=>
UACC-257 NIfBfVRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmfTTWM2OD15LkC0OVEzKM7:TR?= MVnTRW5IWkWU
KM-H2 Mm[xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVjOPHl{UUN3ME23MlE5PDV5IN88US=> M1ixR3NCVkeURWK=
NCI-H1436 NXPCO4kyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoPMTWM2OD15Lk[5PVMzKM7:TR?= NUXTPWtFW0GQR2LFVi=>
IA-LM MkPZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVPJR|UxRTdwOEW5JO69VQ>? NIjXPWVUSU6JUlXS
NCI-H526 NEXLe2RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NETKS4xKSzVyPUiuNlU3OzdizszN M2Gz[3NCVkeURWK=
GCIY M2G4O2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWHJR|UxRThwM{[5OlUh|ryP NVz3UZdtW0GQR2LFVi=>
CP67-MEL Mn73S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVfJR|UxRThwNUOyOkDPxE1? NVWzSFR1W0GQR2LFVi=>
KALS-1 NXrUXVl5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXjJR|UxRThwOEO4OVEh|ryP NFrsNGpUSU6JUlXS
NCI-H1770 M2XHeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGXpcFlKSzVyPUiuPVAzPjVizszN NIOzS4hUSU6JUlXS
8-MG-BA NV3zV3Z{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnT0TWM2OD17LkOyPFQ1KM7:TR?= M{fVRnNCVkeURWK=
KY821 NI\ndGlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnnETWM2OD17Lke3OFg1KM7:TR?= M1;ESHNCVkeURWK=
SNB75 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVzJR|UxRTFyLkC3OkDPxE1? MXXTRW5IWkWU
NCCIT MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoXWTWM2OD1zMT6wOVgzKM7:TR?= M3zYeHNCVkeURWK=
SJSA-1 Mni3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVHJR|UxRTFzLkK4PVEh|ryP NHSzN4lUSU6JUlXS
LB373-MEL-D MorUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVLJR|UxRTFzLkO4Nlch|ryP MnnSV2FPT1KHUh?=
TALL-1 NXLteW83T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mkn2TWM2OD1zMT60NFU5KM7:TR?= MknUV2FPT1KHUh?=
NB69 NFXEe3ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGTmNXBKSzVyPUGxMlc4ODVizszN MV\TRW5IWkWU
NCI-H1355 Mly1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnHDTWM2OD1zMT65OFI3KM7:TR?= NHrMcm5USU6JUlXS
DMS-153 MkHiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NY\YSYJpUUN3ME2xNk4xPDJ4IN88US=> Ml;pV2FPT1KHUh?=
OPM-2 MkPiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGfLS4RKSzVyPUGyMlE2QTZizszN NV33fGVbW0GQR2LFVi=>
NB1 MkLoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3HTTmlEPTB;MUKuNlkh|ryP MYDTRW5IWkWU
A3-KAW NVHwZXNuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlL2TWM2OD1zMj6zNlM3KM7:TR?= NXz1coJDW0GQR2LFVi=>
NCI-H1882 NWDwXmVIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHKxU2pKSzVyPUGyMlQxPjZizszN M{i4RXNCVkeURWK=
KG-1 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUG4b|RTUUN3ME2xNk43PTR3IN88US=> NIW4SYlUSU6JUlXS
LC4-1 MmP1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3ezeGlEPTB;MUKuO|cxPiEQvF2= M1\tU3NCVkeURWK=
HCE-T M1jpbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NF;nZ|NKSzVyPUGzMlAxPDlizszN MUDTRW5IWkWU
NEC8 NIL4dGtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnXyTWM2OD1zMz6xNFM5KM7:TR?= MmnEV2FPT1KHUh?=
IST-MEL1 M1TjZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHj6RZlKSzVyPUGzMlU4QDhizszN Mly0V2FPT1KHUh?=
EW-3 NEnBO2hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWLqb4ZjUUN3ME2xN{44PDB{IN88US=> MUDTRW5IWkWU
CTB-1 NYLNcnRtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIjW[4JKSzVyPUG0MlA{OjlizszN NULkNIpzW0GQR2LFVi=>
LS-123 MkTtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYXJR|UxRTF2LkG1PFgh|ryP MoX3V2FPT1KHUh?=
NCI-H1417 MmXZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWTaNWlqUUN3ME2xOE4{ODV{IN88US=> Mlf4V2FPT1KHUh?=
MZ7-mel NUDFPGt6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX;JR|UxRTF2LkS0N|Mh|ryP Mkf6V2FPT1KHUh?=
JiyoyeP-2003 NESyXIZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXr6PJNkUUN3ME2xOU43OzJ4IN88US=> NYrOcGJXW0GQR2LFVi=>
ES6 M1\aOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXnBS2tSUUN3ME2xOk4zOzZzIN88US=> NWnQTY1IW0GQR2LFVi=>
HH M1Pq[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV31UXpqUUN3ME2xO{4yQTZ|IN88US=> NWm5NGFGW0GQR2LFVi=>
SF539 M{LWW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUXJR|UxRTF5Lkm5NlIh|ryP Mm\FV2FPT1KHUh?=
Calu-6 NF3IUYlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX7JR|UxRTF7LkKzPUDPxE1? MorlV2FPT1KHUh?=
SK-MM-2 M3fXcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmnKTWM2OD1zOT61OVUh|ryP MWHTRW5IWkWU
IST-MES1 NI\YbpdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX7JR|UxRTF7Lk[2OlMh|ryP NY[1V2xEW0GQR2LFVi=>
GI-ME-N NVT3PVQ4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYXJR|UxRTF7LkiyNlch|ryP NIKwellUSU6JUlXS
CAL-148 MmfWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmnrTWM2OD1{MD65PVM1KM7:TR?= M3uwUXNCVkeURWK=
EVSA-T NILGd2pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX\JR|UxRTJzLkG0PVkh|ryP MnzRV2FPT1KHUh?=
LP-1 MnviS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX\JR|UxRTJzLkO0N|Ih|ryP MkK5V2FPT1KHUh?=
BOKU M4nmTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVXJR|UxRTJzLkS1N|Mh|ryP Mn7MV2FPT1KHUh?=
KLE NHT3OJpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlPvTWM2OD1{Mj6xPVA{KM7:TR?= MUDTRW5IWkWU
LB831-BLC MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGrnbGpKSzVyPUK1MlE2OjZizszN NIjOUm5USU6JUlXS
NCI-H889 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlHITWM2OD1{NT6xPVMyKM7:TR?= NXP6WG8{W0GQR2LFVi=>
REH NFHSbphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIHWNnRKSzVyPUK1MlQ3PzFizszN MV\TRW5IWkWU
KP-N-RT-BM-1 MnzyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3rRZWlEPTB;MkWuOFc2OiEQvF2= NIThR3hUSU6JUlXS
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no-11 MkLxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3K5[mlEPTB;MkWuO|Q4KM7:TR?= MkW2V2FPT1KHUh?=
NCI-H748 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmTqTWM2OD1{NT63OlI4KM7:TR?= M3vhRXNCVkeURWK=
LB2518-MEL MnmwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIfPU2hKSzVyPUK3MlE4PzNizszN NUXhPXE2W0GQR2LFVi=>
TGBC1TKB MoqyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIDIeGhKSzVyPUK3MlU2QDVizszN NFLhZ2NUSU6JUlXS
MHH-PREB-1 MlLkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXjJR|UxRTJ6LkC3N|Qh|ryP MWjTRW5IWkWU
MZ2-MEL NF\hb3NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVvJR|UxRTJ6Lk[xOFMh|ryP MV;TRW5IWkWU
U-266 NYHG[mxmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF;2RoRKSzVyPUK4MlY{PjZizszN M4XVO3NCVkeURWK=
SNU-C1 MnnYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M13kVWlEPTB;MkiuPVQ{KM7:TR?= NXj3RWlqW0GQR2LFVi=>
SW962 NEXSO5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoPzTWM2OD1|MD6yO|Q4KM7:TR?= M1n0TnNCVkeURWK=
Raji Ml3hS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYPJR|UxRTNyLkW1PVIh|ryP MXvTRW5IWkWU
KNS-42 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3T4emlEPTB;M{CuPFk2PiEQvF2= MnnpV2FPT1KHUh?=
LB996-RCC M4HwZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWTJR|UxRTNzLkG3NFIh|ryP NUPteGw6W0GQR2LFVi=>
CHP-126 MnjnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4rkN2lEPTB;M{GuNVk5PCEQvF2= M2XKTHNCVkeURWK=
RXF393 MnzKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWLHd5pQUUN3ME2zNk41QTdizszN NV3FXIZ[W0GQR2LFVi=>
COLO-684 NYDNO4hCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFHqNZhKSzVyPUOyMlY1OzhizszN NFjx[JJUSU6JUlXS
A704 NFntPGtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnzSTWM2OD1|Mz61OVM5KM7:TR?= M4XPSHNCVkeURWK=
A253 M4XGR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml;MTWM2OD1|Mz61PFUzKM7:TR?= NFzIcmxUSU6JUlXS
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TE-441-T MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX7WVmhRUUN3ME2zOE43OzdzIN88US=> NWPwNotoW0GQR2LFVi=>
HCC2157 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUHJR|UxRTN3LkS2NVkh|ryP MUnTRW5IWkWU
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NCI-H1155 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2foXWlEPTB;M{euPFE2KM7:TR?= MlTOV2FPT1KHUh?=
SNU-C2B MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUDPOop{UUN3ME2zPE4yPjV2IN88US=> MkPvV2FPT1KHUh?=
JAR MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVTVN5ZEUUN3ME2zPE4zPDR7IN88US=> MU\TRW5IWkWU
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KU812 NHTtUIRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIjCXphKSzVyPUSxMlUxPyEQvF2= NFTreWhUSU6JUlXS
BC-1 MnvPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{fZPGlEPTB;NEKuOlc{OSEQvF2= NVnURWR7W0GQR2LFVi=>
GI-1 M{XPemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFvBUWRKSzVyPUSyMlkyQTJizszN NGfIXIFUSU6JUlXS
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DG-75 NVj3NnJnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{fjbmlEPTB;NEWuNVU4PyEQvF2= MlzyV2FPT1KHUh?=
COR-L88 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkC2TWM2OD12NT6yO|c5KM7:TR?= NHTIRWJUSU6JUlXS
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L-363 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2S5RWlEPTB;NE[uPFgyKM7:TR?= MUnTRW5IWkWU
TE-6 NV32[JJFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXzJR|UxRTR6LkS0OkDPxE1? NYPZXWJSW0GQR2LFVi=>
NCI-H345 MoCxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NG\nbXZKSzVyPUS4MlQ3QCEQvF2= NHnwR2RUSU6JUlXS
TE-5 NYD3UJFuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mlr3TWM2OD12OT63NVE5KM7:TR?= Mlf1V2FPT1KHUh?=

... Click to View More Cell Line Experimental Data

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]

+ Expand

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]

+ Expand
  • 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]

+ Expand
  • Animal Models: Female athymic NCr-nu mice bearing HL-60 leukemia cells
  • Formulation: 50% PEG300 in 50 mM phosphate buffer
  • 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 individually and in order:
5% DMSO+30% PEG 300+2% Tween 80+ddH2O
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
Synonyms N/A

Bio Calculators

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Molarity Calculator

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

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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).

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Dilution Calculator

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

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00500006 Terminated Chronic Myelogenous Leukemia|Leukemia, Lymphoblastic, Acute, Philadelphia-Positive Merck Sharp & Dohme Corp. October 2007 Phase 1
NCT00405054 Terminated Leukemia Merck Sharp & Dohme Corp. December 2006 Phase 2
NCT00290550 Terminated Carcinoma, Non-Small-Cell Lung Merck Sharp & Dohme Corp. June 2006 Phase 2
NCT00111683 Completed Chronic Myelogenous Leukemia in Blast Crisis|Lymphocytic Leukemia, B Cell, Acute|Myelodysplastic Syndromes|Myelogenous Leukemia, Chronic Merck Sharp & Dohme Corp. June 2005 Phase 1
NCT02532868 Terminated Cancer Merck Sharp & Dohme Corp. May 2005 Phase 1
NCT00099346 Terminated Colorectal Cancer|Advanced Solid Tumors Merck Sharp & Dohme Corp. January 2005 Phase 1

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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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID