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 38 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.

    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.

     

    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.

  • 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 NXuyeoZuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlHpTWM2OD1yLkCwN|M5KM7:TR?= NVz1UlN4W0GQR2LFVi=>
RS4-11 M2fvc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnLnTWM2OD1yLkCwOFA1KM7:TR?= NITUTlJUSU6JUlXS
MFH-ino NX\XNWZyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYLuO5VnUUN3ME2wMlAxQTlizszN Mm\6V2FPT1KHUh?=
NTERA-S-cl-D1 MmnlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEewb2ZKSzVyPUCuNFE1OzRizszN MonyV2FPT1KHUh?=
697 NEPBR2pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWHJR|UxRTBwMEK0O|Eh|ryP MW\TRW5IWkWU
NALM-6 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkS4TWM2OD1yLkCyOVUzKM7:TR?= NWDLWnFtW0GQR2LFVi=>
ES8 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkHOTWM2OD1yLkC0OlE{KM7:TR?= MYXTRW5IWkWU
HUTU-80 NF:4fYRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF\XS4ZKSzVyPUCuNFUzQTlizszN NUTKUFBRW0GQR2LFVi=>
MV-4-11 Mn7vS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1;6VGlEPTB;MD6wO|c5OiEQvF2= MVTTRW5IWkWU
MONO-MAC-6 NFezWItIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmS5TWM2OD1yLkC3PFc6KM7:TR?= MlfNV2FPT1KHUh?=
LC-2-ad NGrUPG5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkHsTWM2OD1yLkC4O|g6KM7:TR?= M4LrfHNCVkeURWK=
BL-41 NEXJWm9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX7JR|UxRTBwMUC0OFUh|ryP M1qxVXNCVkeURWK=
A4-Fuk MnHZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoXWTWM2OD1yLkGxOVY{KM7:TR?= M{jT[nNCVkeURWK=
SW954 Ml;4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYLS[lFQUUN3ME2wMlEzOjJ7IN88US=> MWPTRW5IWkWU
BV-173 Mn3mS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkXYTWM2OD1yLkGyOlQyKM7:TR?= M13wbnNCVkeURWK=
TE-11 Mnz6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3P3XmlEPTB;MD6xOFk5OiEQvF2= M4XxTHNCVkeURWK=
SK-UT-1 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3fySGlEPTB;MD6xOVk3PSEQvF2= NUT0VowyW0GQR2LFVi=>
SIG-M5 MkXpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUnJR|UxRTBwMU[3NFch|ryP MXjTRW5IWkWU
OCUB-M NYfHNXNJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M17OPGlEPTB;MD6xOlk5OyEQvF2= NF7ZUWpUSU6JUlXS
K052 NFLCeVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFjtWmZKSzVyPUCuNVk1QCEQvF2= M3q5UHNCVkeURWK=
VA-ES-BJ M3foW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUjJR|UxRTBwMkCwPFYh|ryP M1[0cnNCVkeURWK=
SW982 M2mw[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGXtXIFKSzVyPUCuNlE{QCEQvF2= M3\tVHNCVkeURWK=
LB647-SCLC M333Nmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYPLVXlzUUN3ME2wMlIyPTJ|IN88US=> NFHETYxUSU6JUlXS
PSN1 M4HJZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWGxN4xbUUN3ME2wMlIzODJ4IN88US=> MY\TRW5IWkWU
BB30-HNC MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGHOXY1KSzVyPUCuNlI2QTFizszN MlzDV2FPT1KHUh?=
ST486 NX;ZeIhKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX;JR|UxRTBwMkOwPFch|ryP NGfpeFRUSU6JUlXS
MOLT-4 NIX0dHhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIHLOYhKSzVyPUCuNlM{OzdizszN MWTTRW5IWkWU
EW-16 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWjDVIw3UUN3ME2wMlI{PzZ6IN88US=> M3jofnNCVkeURWK=
KS-1 NYjkSYlST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIXFdVRKSzVyPUCuNlM4QDVizszN MVnTRW5IWkWU
SR NVPkWWZqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVvJR|UxRTBwMkS1OlQh|ryP M3;SSnNCVkeURWK=
KM12 MkTKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{P0cGlEPTB;MD6yOlM3KM7:TR?= NV\wVFdiW0GQR2LFVi=>
EM-2 NEL2OpVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYHIUnRXUUN3ME2wMlI3PjRzIN88US=> NU\ERWpTW0GQR2LFVi=>
MEG-01 NWfpPHZ[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXez[2FZUUN3ME2wMlI4QDR7IN88US=> M4TRZXNCVkeURWK=
NB13 MkHIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmjCTWM2OD1yLkK3PVg1KM7:TR?= NYDR[YhCW0GQR2LFVi=>
RKO NFXHSYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3ftWGlEPTB;MD6zNFgyOyEQvF2= NFjlTIpUSU6JUlXS
CESS M3fXSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2rXVWlEPTB;MD6zNVMzQCEQvF2= MYfTRW5IWkWU
EoL-1-cell NHiwW|lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1uwfmlEPTB;MD6zN|Q2QSEQvF2= MV;TRW5IWkWU
DOHH-2 NFji[oFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4jLNWlEPTB;MD6zN|c5OSEQvF2= NIrrT2hUSU6JUlXS
A388 NYO2NmdQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHGycY1KSzVyPUCuN|QxQDZizszN NUiwb|ZNW0GQR2LFVi=>
LAMA-84 MnnlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2q1d2lEPTB;MD6zOVE4QCEQvF2= MYXTRW5IWkWU
IMR-5 NIjYb5BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHLpUYxKSzVyPUCuN|U2PCEQvF2= NImxNVlUSU6JUlXS
KARPAS-422 M2XlNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2HZcWlEPTB;MD6zO|I4OiEQvF2= MmLaV2FPT1KHUh?=
MRK-nu-1 M{jYUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2XoOWlEPTB;MD6zPFE{KM7:TR?= NHLsV2VUSU6JUlXS
BL-70 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVnCSXN6UUN3ME2wMlM5QTd2IN88US=> M2flV3NCVkeURWK=
LXF-289 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIjwW2tKSzVyPUCuOFA1ODZizszN MVjTRW5IWkWU
RL95-2 NHzZS3hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M36yNWlEPTB;MD60NFU3PyEQvF2= M{LaN3NCVkeURWK=
QIMR-WIL NYfSe2l3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M336OmlEPTB;MD60NlY4PiEQvF2= MUPTRW5IWkWU
K-562 MlGxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mkn6TWM2OD1yLkSzOFczKM7:TR?= M3zxSHNCVkeURWK=
NCI-H510A MmjzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVzkPG54UUN3ME2wMlQ{QDJ|IN88US=> MXjTRW5IWkWU
NCI-H524 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mo\WTWM2OD1yLkWxNVQ4KM7:TR?= NH\kb2FUSU6JUlXS
KE-37 NYjqPWlyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MW\JR|UxRTBwNUKxNFIh|ryP Mn3QV2FPT1KHUh?=
KP-N-YS M1XlW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV3JR|UxRTBwNUSzPVIh|ryP NWezSoZYW0GQR2LFVi=>
LS-411N M2fEO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2i0ZWlEPTB;MD61O|c2OiEQvF2= M2HJXHNCVkeURWK=
CTV-1 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{fXU2lEPTB;MD61PFc4OyEQvF2= M2\FXHNCVkeURWK=
NCI-SNU-16 M36yU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NELlfmJKSzVyPUCuOlM2PzFizszN M1ntbnNCVkeURWK=
HT-144 MljTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmHDTWM2OD1yLk[zO|k5KM7:TR?= M1\XNHNCVkeURWK=
NCI-H187 NFe2U3FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYTEbGxyUUN3ME2wMlY1OTNizszN MV7TRW5IWkWU
OCI-AML2 NGX2emtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEfYUZJKSzVyPUCuOlQ1ODNizszN MV3TRW5IWkWU
CCRF-CEM NWeyTm5{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEe0OHNKSzVyPUCuOlU{PDZizszN NWXqepJVW0GQR2LFVi=>
ONS-76 M2fWUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFy4cItKSzVyPUCuOlY1PThizszN M2\VWnNCVkeURWK=
IST-SL2 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1\XfmlEPTB;MD63NVk5OiEQvF2= MmT0V2FPT1KHUh?=
NB6 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4fxNGlEPTB;MD63O|I2PCEQvF2= MXnTRW5IWkWU
SK-PN-DW MmPGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlvHTWM2OD1yLke5NVQh|ryP M4DVPHNCVkeURWK=
HCC1599 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWr1[3BzUUN3ME2wMlgxQDd2IN88US=> NXnFR21KW0GQR2LFVi=>
MC116 NG\x[IpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{jySGlEPTB;MD64OVAyOSEQvF2= M1XmT3NCVkeURWK=
TE-15 NF31eolIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFLiWYlKSzVyPUCuPFUxQThizszN MU\TRW5IWkWU
HOP-62 NV3DZolXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHXTcGtKSzVyPUCuPFY{OjlizszN NYHRV29EW0GQR2LFVi=>
TGBC24TKB NFTGeXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH3E[|VKSzVyPUCuPFY{QDVizszN MomzV2FPT1KHUh?=
HCE-4 NF7FRoFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGjUeWNKSzVyPUCuPFgxPjNizszN MX;TRW5IWkWU
ALL-PO MkW3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUjJR|UxRTBwOEixO|Uh|ryP MXPTRW5IWkWU
KGN NWr2TppiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXrJR|UxRTBwOEm5PVUh|ryP NHnVUmlUSU6JUlXS
ML-2 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{fyb2lEPTB;MD65NFI2QSEQvF2= NYfu[ZFrW0GQR2LFVi=>
ES4 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnnsTWM2OD1yLkmxNVI5KM7:TR?= MmW2V2FPT1KHUh?=
SF126 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYrleFZvUUN3ME2wMlk1QDF7IN88US=> NU\3OIw{W0GQR2LFVi=>
SK-N-DZ MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUXlPI54UUN3ME2wMlk3OTh7IN88US=> MXTTRW5IWkWU
HCC1187 M{HONWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUfJR|UxRTFwMEC1NFUh|ryP M{TqPXNCVkeURWK=
DU-4475 NXHye4hrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX3EN4c2UUN3ME2xMlAyPzV4IN88US=> NYD0W5U5W0GQR2LFVi=>
NKM-1 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2\aXmlEPTB;MT6wNlc4PSEQvF2= M2DLTnNCVkeURWK=
HL-60 NWC2UI9mT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmrPTWM2OD1zLkC2OVc1KM7:TR?= M4XsbnNCVkeURWK=
SBC-1 NHK4VFdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXG4SIhiUUN3ME2xMlEzPTR{IN88US=> NWqzSJVkW0GQR2LFVi=>
TE-10 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVHNVpk{UUN3ME2xMlEzQTR4IN88US=> NXXZe|FFW0GQR2LFVi=>
ETK-1 M360dmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUPJR|UxRTFwMUO2NVMh|ryP NV;uZYZ4W0GQR2LFVi=>
HAL-01 NUfWRmp{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mk\tTWM2OD1zLkG2O|A6KM7:TR?= MX7TRW5IWkWU
BB65-RCC NHL0PINIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWPENVgxUUN3ME2xMlE5ODB3IN88US=> MkXDV2FPT1KHUh?=
EW-1 M3HIV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnnPTWM2OD1zLkG4OVYzKM7:TR?= MUfTRW5IWkWU
SK-NEP-1 Mk\MS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NULrWmoyUUN3ME2xMlIyOTFzIN88US=> M2TQZnNCVkeURWK=
SK-LMS-1 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGnjXo1KSzVyPUGuNlIzOTJizszN MXTTRW5IWkWU
DEL M2PxUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIO4W21KSzVyPUGuNlU3PDNizszN MUnTRW5IWkWU
GT3TKB M2jjd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUj0dY1EUUN3ME2xMlI5ODV5IN88US=> NG\FOoRUSU6JUlXS
MOLT-16 M{XMS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEK5Z4RKSzVyPUGuN|U1ODVizszN M1PhcnNCVkeURWK=
CMK MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1\DNWlEPTB;MT60NlEyPyEQvF2= M2\oRXNCVkeURWK=
NB5 M1m3Nmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkfkTWM2OD1zLk[0NlI6KM7:TR?= MVvTRW5IWkWU
NCI-H1963 MmfJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkLUTWM2OD1zLkewOVg{KM7:TR?= M3fHOHNCVkeURWK=
KURAMOCHI NGjvdZpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH\1TohKSzVyPUGuO|g6OTFizszN M2LxXnNCVkeURWK=
TE-8 NWHod4xrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYrJR|UxRTFwOECzOlgh|ryP MV3TRW5IWkWU
NCI-H1304 NWXPe2tbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIXZRXZKSzVyPUGuPFMxPzNizszN MkjXV2FPT1KHUh?=
A101D NVL6XGJFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV;0eGpmUUN3ME2xMlg4Ozl3IN88US=> NVHDZXlGW0GQR2LFVi=>
SCLC-21H MoXiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWPZdHI6UUN3ME2xMlk4ODV5IN88US=> M1HINXNCVkeURWK=
GB-1 MoG4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFu4RYlKSzVyPUKuNFE3PDdizszN MoHTV2FPT1KHUh?=
KARPAS-45 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUK5fpNbUUN3ME2yMlAzPjV2IN88US=> NE[5[IZUSU6JUlXS
ATN-1 NXvZOmROT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2nUdGlEPTB;Mj6wNlg2QCEQvF2= M{LFTHNCVkeURWK=
NCI-H720 NGnYNXJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnfKTWM2OD1{LkC2NlQ1KM7:TR?= NVrFfnlLW0GQR2LFVi=>
RPMI-6666 NI\rbGtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHnsNJlKSzVyPUKuNVYzODdizszN NIfTdG1USU6JUlXS
NB17 NFHIZWRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIrl[m9KSzVyPUKuNlkzPyEQvF2= MYTTRW5IWkWU
IST-SL1 NF3Q[2hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlvPTWM2OD1{LkK5O|Y2KM7:TR?= M2jvfHNCVkeURWK=
SH-4 M{Pwe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXPwPIhyUUN3ME2yMlMzPDZ7IN88US=> NX;qXJhZW0GQR2LFVi=>
K5 NVLae3NiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mon0TWM2OD1{LkSwN|E6KM7:TR?= MlHYV2FPT1KHUh?=
OVCAR-4 MnPDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEGyOZZKSzVyPUKuOFYyOyEQvF2= M2fNSXNCVkeURWK=
ACN NY\4fFI6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFLDflNKSzVyPUKuOVAzOTNizszN Ml7YV2FPT1KHUh?=
TGW NVrFR2lKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn\YTWM2OD1{Lk[1PFMzKM7:TR?= M1[5enNCVkeURWK=
NCI-H2107 M3L2V2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlLRTWM2OD1{LkizO|EyKM7:TR?= MnfpV2FPT1KHUh?=
NCI-H82 M1TLR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXznbld2UUN3ME2yMlg{QDN6IN88US=> Ml;yV2FPT1KHUh?=
SK-N-FI MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlPvTWM2OD1{Lki2PFY5KM7:TR?= MUDTRW5IWkWU
LB1047-RCC NU[2SIRGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYXSRnlsUUN3ME2yMlg5OTJ4IN88US=> NWPGRo9jW0GQR2LFVi=>
LU-134-A M3j4fGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVTJR|UxRTJwOEmyOkDPxE1? NUe3T29{W0GQR2LFVi=>
NCI-H209 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NITrb4pKSzVyPUKuPVEzPTNizszN MnH1V2FPT1KHUh?=
NOMO-1 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVP6b|R2UUN3ME2zMlAzOjd2IN88US=> NELTem1USU6JUlXS
RH-1 NInCWmJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX\JR|UxRTNwMUeyPVEh|ryP MlzNV2FPT1KHUh?=
LOUCY NX\vPYxnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmroTWM2OD1|LkG4Olk{KM7:TR?= MlzDV2FPT1KHUh?=
TE-9 MkPlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX;wTpRWUUN3ME2zMlI3PzN4IN88US=> NUHFcolWW0GQR2LFVi=>
PF-382 NHfqWodIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXrsfHlrUUN3ME2zMlM2Pzd6IN88US=> NGmzPVVUSU6JUlXS
RPMI-8402 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml6wTWM2OD1|LkW4OlA{KM7:TR?= MlLkV2FPT1KHUh?=
HEL NEHsNYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHG5dXNKSzVyPUOuOlMzKM7:TR?= NHfTdGpUSU6JUlXS
NOS-1 NW\EOHRQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mm\JTWM2OD1|Lki0O|U1KM7:TR?= NGXFUJJUSU6JUlXS
ES1 NYrxd2xDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUPrVYwyUUN3ME2zMlkzOjl|IN88US=> NF\0TXNUSU6JUlXS
NCI-H2171 NFe2WIRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYjJR|UxRTNwOUK0NlMh|ryP NW\hT2cyW0GQR2LFVi=>
NCI-H747 Ml\ES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXfJR|UxRTNwOUSyNlEh|ryP M2HkU3NCVkeURWK=
MHH-NB-11 MlPLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnvhTWM2OD1|Lkm1N|EzKM7:TR?= NHK1eXZUSU6JUlXS
MZ1-PC M1XRRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVPJR|UxRTNwOUmyOEDPxE1? MYrTRW5IWkWU
MMAC-SF Mkf1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXG5fGoxUUN3ME20MlAzPDZ5IN88US=> Ml;uV2FPT1KHUh?=
NMC-G1 NFrEZYVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWPJR|UxRTRwMkK3NlMh|ryP MVXTRW5IWkWU
SW872 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2fzcGlEPTB;ND6zOFM1KM7:TR?= MnPvV2FPT1KHUh?=
TE-12 NYDweWZHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVXjS4pTUUN3ME20MlU3Ozl2IN88US=> NWr4fmJxW0GQR2LFVi=>
LU-139 Mkj3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFzMbGpKSzVyPUSuOlE5OzVizszN MljHV2FPT1KHUh?=
HC-1 M{nJRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVTJR|UxRTRwNkm0PVQh|ryP MXTTRW5IWkWU
COR-L279 NFPnb4VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M17GOGlEPTB;ND63OVg6OSEQvF2= Mlr3V2FPT1KHUh?=
SF268 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnPETWM2OD12Lke5PVE3KM7:TR?= NFP5XIJUSU6JUlXS
MC-CAR MoTwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3rMRmlEPTB;NT6wOlc2PyEQvF2= M3K5T3NCVkeURWK=
TK10 NIL5eGpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MonPTWM2OD13LkO1OFY6KM7:TR?= NUHTPG9VW0GQR2LFVi=>
TE-1 M{\LTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYLJR|UxRTVwNEmwNFQh|ryP MYTTRW5IWkWU
NCI-H2126 NWDENopUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUfJR|UxRTVwNkS1O|Qh|ryP NIO2OJVUSU6JUlXS
Daudi MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIL1WZhKSzVyPUWuOlkyOiEQvF2= NFTSWpVUSU6JUlXS
NCI-H1648 NHzvSpZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEeybmxKSzVyPUWuPFE1PTRizszN NUPyepIxW0GQR2LFVi=>
OS-RC-2 M4nwUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkLETWM2OD13Lkm4OVk4KM7:TR?= MnvSV2FPT1KHUh?=
DJM-1 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn7LTWM2OD14LkO0OlY3KM7:TR?= NXLv[GJpW0GQR2LFVi=>
LS-1034 NV34UHNkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYjiepBoUUN3ME22Mlc2PjZizszN NEnheYVUSU6JUlXS
NCI-H1581 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml7hTWM2OD14Lke4OFA2KM7:TR?= NUC4XIljW0GQR2LFVi=>
UACC-257 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUf1dZFrUUN3ME23MlA1PTF{IN88US=> NV\LVpRXW0GQR2LFVi=>
KM-H2 NIHLe|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnTjTWM2OD15LkG4OFU4KM7:TR?= NWT2d29MW0GQR2LFVi=>
NCI-H1436 MlPMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUDYSG5iUUN3ME23MlY6QTN{IN88US=> NY\GZnRFW0GQR2LFVi=>
IA-LM M{PmcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFXqRYtKSzVyPUeuPFU6KM7:TR?= M33XWnNCVkeURWK=
NCI-H526 Mnj4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlfHTWM2OD16LkK1OlM4KM7:TR?= NIT1OIpUSU6JUlXS
GCIY M2rOO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MY\JR|UxRThwM{[5OlUh|ryP NHTNcHRUSU6JUlXS
CP67-MEL NHTNTXFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVvJR|UxRThwNUOyOkDPxE1? NV6yPXdXW0GQR2LFVi=>
KALS-1 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWXoSYRUUUN3ME24Mlg{QDVzIN88US=> MlTGV2FPT1KHUh?=
NCI-H1770 Mmr6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnfBTWM2OD16LkmwNlY2KM7:TR?= M4D2bXNCVkeURWK=
8-MG-BA MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlTFTWM2OD17LkOyPFQ1KM7:TR?= NVLvcm1CW0GQR2LFVi=>
KY821 NHP6WWRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGXFOmNKSzVyPUmuO|c1QDRizszN NH\nd25USU6JUlXS
SNB75 NYTzOJpbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWrMVFFjUUN3ME2xNE4xPzZizszN NFK3SVdUSU6JUlXS
NCCIT MmHVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWrweYprUUN3ME2xNU4xPTh{IN88US=> MlLtV2FPT1KHUh?=
SJSA-1 M1vEbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVHJR|UxRTFzLkK4PVEh|ryP NYLpSGR5W0GQR2LFVi=>
LB373-MEL-D MmnYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1rlXGlEPTB;MUGuN|gzPyEQvF2= M3jrNnNCVkeURWK=
TALL-1 NFW2fXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4rVdGlEPTB;MUGuOFA2QCEQvF2= NFTwWGJUSU6JUlXS
NB69 MkTJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlvUTWM2OD1zMT63O|A2KM7:TR?= M{KxR3NCVkeURWK=
NCI-H1355 MoHWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEjlVlZKSzVyPUGxMlk1OjZizszN M4jL[3NCVkeURWK=
DMS-153 NGTkRplIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4HKWGlEPTB;MUKuNFQzPiEQvF2= NVvMcWl{W0GQR2LFVi=>
OPM-2 NFXO[ZNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUjJR|UxRTF{LkG1PVYh|ryP M4LpbHNCVkeURWK=
NB1 M1PqT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWHJR|UxRTF{LkK5JO69VQ>? NWrxN45lW0GQR2LFVi=>
A3-KAW M2DHNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHS5ZVBKSzVyPUGyMlMzOzZizszN MXvTRW5IWkWU
NCI-H1882 M4fCUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWfJR|UxRTF{LkSwOlYh|ryP NIDhR|lUSU6JUlXS
KG-1 NYTzOZIxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmfZTWM2OD1zMj62OVQ2KM7:TR?= Mo[zV2FPT1KHUh?=
LC4-1 MkDNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4riOGlEPTB;MUKuO|cxPiEQvF2= NXqwbWZLW0GQR2LFVi=>
HCE-T M2W4R2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml24TWM2OD1zMz6wNFQ6KM7:TR?= NVLIPWJ4W0GQR2LFVi=>
NEC8 NFfr[HpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXfJR|UxRTF|LkGwN|gh|ryP MoLOV2FPT1KHUh?=
IST-MEL1 NV7WSmZkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIOyTotKSzVyPUGzMlU4QDhizszN NH;rO2RUSU6JUlXS
EW-3 M2PpXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVTJR|UxRTF|Lke0NFIh|ryP NUPQ[25mW0GQR2LFVi=>
CTB-1 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1jWeWlEPTB;MUSuNFMzQSEQvF2= NYrFUXp1W0GQR2LFVi=>
LS-123 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUfJR|UxRTF2LkG1PFgh|ryP M1S5WnNCVkeURWK=
NCI-H1417 NXrRRVhxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH\tOVFKSzVyPUG0MlMxPTJizszN M2Hl[XNCVkeURWK=
MZ7-mel M1;uO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXjJR|UxRTF2LkS0N|Mh|ryP NGrTfHZUSU6JUlXS
JiyoyeP-2003 NYnldm9WT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkDhTWM2OD1zNT62N|I3KM7:TR?= NULhVldPW0GQR2LFVi=>
ES6 NHfrWlRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEDsUGRKSzVyPUG2MlI{PjFizszN NWH3fWtWW0GQR2LFVi=>
HH M3fFUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4rHPGlEPTB;MUeuNVk3OyEQvF2= NXjj[VFkW0GQR2LFVi=>
SF539 NYS4TZZtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml3aTWM2OD1zNz65PVIzKM7:TR?= NF\Vb4JUSU6JUlXS
Calu-6 NEjJN2dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXnyWIFmUUN3ME2xPU4zOzlizszN NU\ReXdGW0GQR2LFVi=>
SK-MM-2 M2G1Wmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUP5OJJpUUN3ME2xPU42PTVizszN NIj4PXVUSU6JUlXS
IST-MES1 NFjzR45Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUPGfI9VUUN3ME2xPU43PjZ|IN88US=> MWTTRW5IWkWU
GI-ME-N NWfzV2RoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlPqTWM2OD1zOT64NlI4KM7:TR?= MlLzV2FPT1KHUh?=
CAL-148 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXy0Und{UUN3ME2yNE46QTN2IN88US=> NFvZbGFUSU6JUlXS
EVSA-T M4fHSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M13JcWlEPTB;MkGuNVQ6QSEQvF2= MnO4V2FPT1KHUh?=
LP-1 NH7HO3JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWXJR|UxRTJzLkO0N|Ih|ryP MVTTRW5IWkWU
BOKU NUftc49uT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3;6TWlEPTB;MkGuOFU{OyEQvF2= NWn4eYFyW0GQR2LFVi=>
KLE NX70SXR4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{i3W2lEPTB;MkKuNVkxOyEQvF2= M1vmcnNCVkeURWK=
LB831-BLC MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2jSUmlEPTB;MkWuNVUzPiEQvF2= M4PMfXNCVkeURWK=
NCI-H889 NXP0VoYyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVLPNW9MUUN3ME2yOU4yQTNzIN88US=> MYrTRW5IWkWU
REH M1;wVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFHrbmdKSzVyPUK1MlQ3PzFizszN NW\nO5lIW0GQR2LFVi=>
KP-N-RT-BM-1 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkTjTWM2OD1{NT60O|UzKM7:TR?= MUXTRW5IWkWU
MPP-89 M1LOVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVrVRYljUUN3ME2yOU42OzF2IN88US=> M3fLV3NCVkeURWK=
no-11 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVHJR|UxRTJ3Lke0O{DPxE1? MnXFV2FPT1KHUh?=
NCI-H748 NH;aS5pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3f1bGlEPTB;MkWuO|YzPyEQvF2= NX\zZ49WW0GQR2LFVi=>
LB2518-MEL MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXfPSHpiUUN3ME2yO{4yPzd|IN88US=> NV7tUmJbW0GQR2LFVi=>
TGBC1TKB MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXiwT2dZUUN3ME2yO{42PTh3IN88US=> NWq0VJQ4W0GQR2LFVi=>
MHH-PREB-1 NHfRbpBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUfJR|UxRTJ6LkC3N|Qh|ryP NGfPR21USU6JUlXS
MZ2-MEL MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoHyTWM2OD1{OD62NVQ{KM7:TR?= Mo\SV2FPT1KHUh?=
U-266 NImxcnpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mnj5TWM2OD1{OD62N|Y3KM7:TR?= NUPkcGhmW0GQR2LFVi=>
SNU-C1 MmfZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUTRVFExUUN3ME2yPE46PDNizszN M4LZNXNCVkeURWK=
SW962 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{LZNmlEPTB;M{CuNlc1PyEQvF2= MX3TRW5IWkWU
Raji NEGxN3RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXG0VYF{UUN3ME2zNE42PTl{IN88US=> NW\GXllTW0GQR2LFVi=>
KNS-42 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3\SeWlEPTB;M{CuPFk2PiEQvF2= NV\iSoN4W0GQR2LFVi=>
LB996-RCC Ml[0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVXBUlNFUUN3ME2zNU4yPzB{IN88US=> NVH2TpZZW0GQR2LFVi=>
CHP-126 NH7FeldIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MljkTWM2OD1|MT6xPVg1KM7:TR?= NGnCTGtUSU6JUlXS
RXF393 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3\VPWlEPTB;M{KuOFk4KM7:TR?= MYnTRW5IWkWU
COLO-684 NEjSRXZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn;XTWM2OD1|Mj62OFM5KM7:TR?= NYizSJJGW0GQR2LFVi=>
A704 NYPJSVZFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXTNW2V{UUN3ME2zN{42PTN6IN88US=> M{nD[3NCVkeURWK=
A253 MoLHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIXFW5VKSzVyPUOzMlU5PTJizszN M3i2XnNCVkeURWK=
KNS-81-FD MmqwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2HWXGlEPTB;M{SuOVQ2PiEQvF2= MV3TRW5IWkWU
TE-441-T NWj3U5p3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4G4dWlEPTB;M{SuOlM4OSEQvF2= M1TXTHNCVkeURWK=
HCC2157 NVvmRlA3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWTyXVlNUUN3ME2zOU41PjF7IN88US=> MmTuV2FPT1KHUh?=
ES3 NHLHbHBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3LNSWlEPTB;M{[uOlc2KM7:TR?= NIH6OotUSU6JUlXS
NCI-H1155 MmjvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1;Qd2lEPTB;M{euPFE2KM7:TR?= MmHrV2FPT1KHUh?=
SNU-C2B M1TseGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH\WNXNKSzVyPUO4MlE3PTRizszN MUDTRW5IWkWU
JAR NV;UeFhPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4HTN2lEPTB;M{iuNlQ1QSEQvF2= MVTTRW5IWkWU
GDM-1 M1e2WGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEHiN4lKSzVyPUO4MlkyOTZizszN MX7TRW5IWkWU
KU812 NFTZOo5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoTGTWM2OD12MT61NFch|ryP M3jYVnNCVkeURWK=
BC-1 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUKwcZYxUUN3ME20Nk43PzNzIN88US=> NGDrdphUSU6JUlXS
GI-1 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGL1O4VKSzVyPUSyMlkyQTJizszN NIrTS29USU6JUlXS
NCI-H1694 MoqxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGm0RXpKSzVyPUS0Mlk1PzJizszN Mo\MV2FPT1KHUh?=
DG-75 NIHQW4NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVzCU2tZUUN3ME20OU4yPTd5IN88US=> M1Tpe3NCVkeURWK=
COR-L88 NHy3UmhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUXwR5BYUUN3ME20OU4zPzd6IN88US=> M3TIOXNCVkeURWK=
LS-513 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4DaS2lEPTB;NEWuPVE2PiEQvF2= M3O4W3NCVkeURWK=
HD-MY-Z MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX76OYVIUUN3ME20Ok41PjF{IN88US=> MoPCV2FPT1KHUh?=
L-363 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NELheFBKSzVyPUS2Mlg5OSEQvF2= NWXWOmsxW0GQR2LFVi=>
TE-6 MoPXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXTJR|UxRTR6LkS0OkDPxE1? MYjTRW5IWkWU
NCI-H345 NWP4UGpGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUDJR|UxRTR6LkS2PEDPxE1? M{j4SHNCVkeURWK=
TE-5 M2DsWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH6zbo5KSzVyPUS5MlcyOThizszN NH3ROG9USU6JUlXS

... 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 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

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:

Mass (g) = Concentration (mol/L) × Volume (L) × 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)

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

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Mass Concentration Volume Molecular Weight

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
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
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
NCT00290550 Terminated Carcinoma Non-Small-Cell Lung Merck Sharp & Dohme Corp. June 2006 Phase 2

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

Aurora Kinase Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID