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 M1jpXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHuyfZFKSzVyPUCuNFA{OzhizszN NX3vSm1ZW0GQR2LFVi=>
RS4-11 MmTpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MY\JR|UxRTBwMEC0NFQh|ryP NYDxXnAzW0GQR2LFVi=>
MFH-ino NYTQfJk6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4i4NmlEPTB;MD6wNFk6KM7:TR?= M3\CRXNCVkeURWK=
NTERA-S-cl-D1 MoL6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVLJR|UxRTBwMEG0N|Qh|ryP MnXIV2FPT1KHUh?=
697 MmfMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHXqXppKSzVyPUCuNFI1PzFizszN M1zDSHNCVkeURWK=
NALM-6 M{XEOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYrJR|UxRTBwMEK1OVIh|ryP M{e2UHNCVkeURWK=
ES8 Ml3DS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXvJR|UxRTBwMES2NVMh|ryP NHjiZWdUSU6JUlXS
HUTU-80 Ml3KS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHT1SIRKSzVyPUCuNFUzQTlizszN MUnTRW5IWkWU
MV-4-11 MnK5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1Pkd2lEPTB;MD6wO|c5OiEQvF2= NFvxZWNUSU6JUlXS
MONO-MAC-6 NVKzTnZmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFj1dnlKSzVyPUCuNFc5PzlizszN NF;uVoFUSU6JUlXS
LC-2-ad Mnm4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHvIfIlKSzVyPUCuNFg4QDlizszN MYHTRW5IWkWU
BL-41 NVnPUnpFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVjJR|UxRTBwMUC0OFUh|ryP NGroT4RUSU6JUlXS
A4-Fuk MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2TYZmlEPTB;MD6xNVU3OyEQvF2= M2DOUXNCVkeURWK=
SW954 NHTCNm1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGH6eG1KSzVyPUCuNVIzOjlizszN NW\SRYJpW0GQR2LFVi=>
BV-173 NYmxboM{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkfrTWM2OD1yLkGyOlQyKM7:TR?= MYHTRW5IWkWU
TE-11 NV\hZW84T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXPJR|UxRTBwMUS5PFIh|ryP MWjTRW5IWkWU
SK-UT-1 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkDKTWM2OD1yLkG1PVY2KM7:TR?= NVjFepdWW0GQR2LFVi=>
SIG-M5 MlnXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGXWVJdKSzVyPUCuNVY4ODdizszN M2OzRnNCVkeURWK=
OCUB-M NVSyfVVqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWfJVI1mUUN3ME2wMlE3QTh|IN88US=> NIfQendUSU6JUlXS
K052 M1uyUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHK2VFNKSzVyPUCuNVk1QCEQvF2= M{TPPXNCVkeURWK=
VA-ES-BJ NULKPJpjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4\hXGlEPTB;MD6yNFA5PiEQvF2= M2\WTnNCVkeURWK=
SW982 NF7tN2NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{fObWlEPTB;MD6yNVM5KM7:TR?= M{\hO3NCVkeURWK=
LB647-SCLC MnTIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHLjTWhKSzVyPUCuNlE2OjNizszN MYfTRW5IWkWU
PSN1 M1nKcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH35WZhKSzVyPUCuNlIxOjZizszN M1izeXNCVkeURWK=
BB30-HNC NEThXXhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mk\wTWM2OD1yLkKyOVkyKM7:TR?= NF;Bfm5USU6JUlXS
ST486 NH3xV|VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmXRTWM2OD1yLkKzNFg4KM7:TR?= MYXTRW5IWkWU
MOLT-4 NWO1eW5PT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4\I[WlEPTB;MD6yN|M{PyEQvF2= M3T3UHNCVkeURWK=
EW-16 M4TpXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoLxTWM2OD1yLkKzO|Y5KM7:TR?= NWXSXXpWW0GQR2LFVi=>
KS-1 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3LRWWlEPTB;MD6yN|c5PSEQvF2= MVjTRW5IWkWU
SR NVnMUmE5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUHENIJMUUN3ME2wMlI1PTZ2IN88US=> NIf5N29USU6JUlXS
KM12 NYnl[41zT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV\FV2tWUUN3ME2wMlI3OzZizszN M{PPVXNCVkeURWK=
EM-2 MlLYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{LYVGlEPTB;MD6yOlY1OSEQvF2= NWXtR3c{W0GQR2LFVi=>
MEG-01 MknNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3rIbGlEPTB;MD6yO|g1QSEQvF2= MnnUV2FPT1KHUh?=
NB13 M2HHRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXPUdZBuUUN3ME2wMlI4QTh2IN88US=> MXnTRW5IWkWU
RKO NHXiSIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF:3U3dKSzVyPUCuN|A5OTNizszN MY\TRW5IWkWU
CESS NIjvbJVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWK2doR[UUN3ME2wMlMyOzJ6IN88US=> NWrVPIY{W0GQR2LFVi=>
EoL-1-cell MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYnZV3NZUUN3ME2wMlM{PDV7IN88US=> NW\BTFNNW0GQR2LFVi=>
DOHH-2 NIjNRpVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXfJR|UxRTBwM{O3PFEh|ryP Mof4V2FPT1KHUh?=
A388 NX;OVpdDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGjjc4xKSzVyPUCuN|QxQDZizszN NVvFZW0xW0GQR2LFVi=>
LAMA-84 MmTwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEHVfmFKSzVyPUCuN|UyPzhizszN M1:5e3NCVkeURWK=
IMR-5 NEjsNnlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml7vTWM2OD1yLkO1OVQh|ryP MoO4V2FPT1KHUh?=
KARPAS-422 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYLJR|UxRTBwM{eyO|Ih|ryP M1H4S3NCVkeURWK=
MRK-nu-1 Ml:wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYXJR|UxRTBwM{ixN{DPxE1? MkmyV2FPT1KHUh?=
BL-70 NFzObWlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{Dp[GlEPTB;MD6zPFk4PCEQvF2= NXrhV5ppW0GQR2LFVi=>
LXF-289 Mn3uS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnjjTWM2OD1yLkSwOFA3KM7:TR?= M{Kxb3NCVkeURWK=
RL95-2 NV:xdIFxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnfnTWM2OD1yLkSwOVY4KM7:TR?= NW\OfXQzW0GQR2LFVi=>
QIMR-WIL Mn\jS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVLJR|UxRTBwNEK2O|Yh|ryP MYfTRW5IWkWU
K-562 M1:yOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEDDc3NKSzVyPUCuOFM1PzJizszN M{XQdnNCVkeURWK=
NCI-H510A M4ribmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NW\FTIpHUUN3ME2wMlQ{QDJ|IN88US=> M1f3SnNCVkeURWK=
NCI-H524 NUHFdpV1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoX5TWM2OD1yLkWxNVQ4KM7:TR?= NHTyUFNUSU6JUlXS
KE-37 M3PLRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnrCTWM2OD1yLkWyNVAzKM7:TR?= MkT2V2FPT1KHUh?=
KP-N-YS M3HOc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXTJR|UxRTBwNUSzPVIh|ryP NFrFbpBUSU6JUlXS
LS-411N M3PaUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHHVTGVKSzVyPUCuOVc4PTJizszN Mn32V2FPT1KHUh?=
CTV-1 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWnDNHQzUUN3ME2wMlU5Pzd|IN88US=> NIrF[ZdUSU6JUlXS
NCI-SNU-16 NIXWNZpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnXSTWM2OD1yLk[zOVcyKM7:TR?= MWrTRW5IWkWU
HT-144 NFy2bnRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoS2TWM2OD1yLk[zO|k5KM7:TR?= NHmwNYlUSU6JUlXS
NCI-H187 MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUXkdpRZUUN3ME2wMlY1OTNizszN NGfIUHJUSU6JUlXS
OCI-AML2 M2G0Vmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIDT[VZKSzVyPUCuOlQ1ODNizszN MlnZV2FPT1KHUh?=
CCRF-CEM NUnQVXc2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mnj0TWM2OD1yLk[1N|Q3KM7:TR?= M4Sw[HNCVkeURWK=
ONS-76 MnflS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M13SWGlEPTB;MD62OlQ2QCEQvF2= MW\TRW5IWkWU
IST-SL2 MkfUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHTmUo5KSzVyPUCuO|E6QDJizszN NUXGW4JLW0GQR2LFVi=>
NB6 NH7yV4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYrVelZIUUN3ME2wMlc4OjV2IN88US=> NUjt[m5TW0GQR2LFVi=>
SK-PN-DW MmnRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkPjTWM2OD1yLke5NVQh|ryP NW\4b2ZoW0GQR2LFVi=>
HCC1599 NWLhd2k{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYLJR|UxRTBwOEC4O|Qh|ryP NHW2T3lUSU6JUlXS
MC116 NGjqfJZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3ruNGlEPTB;MD64OVAyOSEQvF2= NXjjZm9zW0GQR2LFVi=>
TE-15 MmC4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYLJR|UxRTBwOEWwPVgh|ryP MUTTRW5IWkWU
HOP-62 M335Zmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2jqV2lEPTB;MD64OlMzQSEQvF2= M37xOnNCVkeURWK=
TGBC24TKB NFjENopIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{PvXWlEPTB;MD64OlM5PSEQvF2= NUf3THE6W0GQR2LFVi=>
HCE-4 NWfudopPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml[2TWM2OD1yLki4NFY{KM7:TR?= NEjYcGZUSU6JUlXS
ALL-PO NEXnelRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIrhV|ZKSzVyPUCuPFgyPzVizszN NH\vUWVUSU6JUlXS
KGN NVzVb4hTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYfJR|UxRTBwOEm5PVUh|ryP MmS0V2FPT1KHUh?=
ML-2 M1G1RWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHLsVWRKSzVyPUCuPVAzPTlizszN M17TVnNCVkeURWK=
ES4 NWjXOpdnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX3JR|UxRTBwOUGxNlgh|ryP MWnTRW5IWkWU
SF126 M2LPfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHz6SG5KSzVyPUCuPVQ5OTlizszN Mk\ZV2FPT1KHUh?=
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HCC1187 NXHnNFhVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXTJR|UxRTFwMEC1NFUh|ryP MWTTRW5IWkWU
DU-4475 M3vDRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml;GTWM2OD1zLkCxO|U3KM7:TR?= MmHvV2FPT1KHUh?=
NKM-1 MlLpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXLpT4Z5UUN3ME2xMlAzPzd3IN88US=> NYC2cWd7W0GQR2LFVi=>
HL-60 MnPtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoDWTWM2OD1zLkC2OVc1KM7:TR?= NULDfJpCW0GQR2LFVi=>
SBC-1 M2jkcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUPJR|UxRTFwMUK1OFIh|ryP MX3TRW5IWkWU
TE-10 NFX0UnlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MljuTWM2OD1zLkGyPVQ3KM7:TR?= NXvQdVF{W0GQR2LFVi=>
ETK-1 NHrRZXhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4Ls[mlEPTB;MT6xN|YyOyEQvF2= MX\TRW5IWkWU
HAL-01 NWrNTYhpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1u4VWlEPTB;MT6xOlcxQSEQvF2= MYXTRW5IWkWU
BB65-RCC NWLMSFVkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2DDS2lEPTB;MT6xPFAxPSEQvF2= NFnTVnVUSU6JUlXS
EW-1 MljiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHH5bJRKSzVyPUGuNVg2PjJizszN NXfveJBLW0GQR2LFVi=>
SK-NEP-1 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2nFcWlEPTB;MT6yNVEyOSEQvF2= M13IV3NCVkeURWK=
SK-LMS-1 NEPZR5lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXfzeHZIUUN3ME2xMlIzOjF{IN88US=> MXrTRW5IWkWU
DEL M1XyNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVvGSpVPUUN3ME2xMlI2PjR|IN88US=> Ml21V2FPT1KHUh?=
GT3TKB MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn3tTWM2OD1zLkK4NFU4KM7:TR?= NUDjO4t3W0GQR2LFVi=>
MOLT-16 NXS4fIZ2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEnrNpNKSzVyPUGuN|U1ODVizszN M3LUeXNCVkeURWK=
CMK MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUTSNlBoUUN3ME2xMlQzOTF5IN88US=> NWCzW417W0GQR2LFVi=>
NB5 MlHNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NICx[ZRKSzVyPUGuOlQzOjlizszN MYXTRW5IWkWU
NCI-H1963 MnO1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVzJR|UxRTFwN{C1PFMh|ryP NUS2OYR6W0GQR2LFVi=>
KURAMOCHI MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVTJR|UxRTFwN{i5NVEh|ryP MY\TRW5IWkWU
TE-8 MkHCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUjhWJRjUUN3ME2xMlgxOzZ6IN88US=> NYfYbI9DW0GQR2LFVi=>
NCI-H1304 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnnJTWM2OD1zLkizNFc{KM7:TR?= NHzvbVBUSU6JUlXS
A101D MnrIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml7STWM2OD1zLki3N|k2KM7:TR?= NHfPcpBUSU6JUlXS
SCLC-21H MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX3re3hKUUN3ME2xMlk4ODV5IN88US=> NGLIOldUSU6JUlXS
GB-1 Mo\ES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUDMU4VNUUN3ME2yMlAyPjR5IN88US=> NXzhSJBqW0GQR2LFVi=>
KARPAS-45 NYW5Zm1{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NELVbFlKSzVyPUKuNFI3PTRizszN M3jCW3NCVkeURWK=
ATN-1 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoW0TWM2OD1{LkCyPFU5KM7:TR?= Mo\oV2FPT1KHUh?=
NCI-H720 NYDZWGFpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEOycYtKSzVyPUKuNFYzPDRizszN NWqxVotuW0GQR2LFVi=>
RPMI-6666 NFjmflhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGfN[pJKSzVyPUKuNVYzODdizszN M1;pOXNCVkeURWK=
NB17 M{f3Z2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYnCclR{UUN3ME2yMlI6OjdizszN MoTvV2FPT1KHUh?=
IST-SL1 MoPkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoXuTWM2OD1{LkK5O|Y2KM7:TR?= NHLzOlRUSU6JUlXS
SH-4 NEf3blNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFzvRVJKSzVyPUKuN|I1PjlizszN NEfHcohUSU6JUlXS
K5 NY[xb5BFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUHJR|UxRTJwNECzNVkh|ryP M{fwOnNCVkeURWK=
OVCAR-4 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1HHbmlEPTB;Mj60OlE{KM7:TR?= NX:3bXhNW0GQR2LFVi=>
ACN M1j2UGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2fle2lEPTB;Mj61NFIyOyEQvF2= NWm4NlhpW0GQR2LFVi=>
TGW MmHjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHLyNGtKSzVyPUKuOlU5OzJizszN NV3pVJlKW0GQR2LFVi=>
NCI-H2107 MmDxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NG\qWHVKSzVyPUKuPFM4OTFizszN NXjpWYRQW0GQR2LFVi=>
NCI-H82 M{SxVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4njOmlEPTB;Mj64N|g{QCEQvF2= M2TYT3NCVkeURWK=
SK-N-FI MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4\OTGlEPTB;Mj64Olg3QCEQvF2= MkTUV2FPT1KHUh?=
LB1047-RCC MmfrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXPJR|UxRTJwOEixNlYh|ryP NVrhU5o1W0GQR2LFVi=>
LU-134-A M1vLTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MW\JR|UxRTJwOEmyOkDPxE1? MVTTRW5IWkWU
NCI-H209 Mk\1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWXJR|UxRTJwOUGyOVMh|ryP Mn2yV2FPT1KHUh?=
NOMO-1 M2rXUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUPWeW9OUUN3ME2zMlAzOjd2IN88US=> NELUT3RUSU6JUlXS
RH-1 M{OzTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MW\JR|UxRTNwMUeyPVEh|ryP MoPpV2FPT1KHUh?=
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TE-9 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEnuZ2pKSzVyPUOuNlY4OzZizszN NYnLSJU6W0GQR2LFVi=>
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RPMI-8402 NI\yUGpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHvJSZJKSzVyPUOuOVg3ODNizszN NXTpSWt5W0GQR2LFVi=>
HEL M3zqV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXvJR|UxRTNwNkOyJO69VQ>? MX3TRW5IWkWU
NOS-1 NHGxSJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlvLTWM2OD1|Lki0O|U1KM7:TR?= MmnuV2FPT1KHUh?=
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NCI-H2171 M2S1[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4\seWlEPTB;Mz65NlQzOyEQvF2= NFziR|dUSU6JUlXS
NCI-H747 M{fBZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkXmTWM2OD1|Lkm0NlIyKM7:TR?= MXLTRW5IWkWU
MHH-NB-11 NIjicmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWfiU2dRUUN3ME2zMlk2OzF{IN88US=> MoPGV2FPT1KHUh?=
MZ1-PC NH\VT2lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3HoXmlEPTB;Mz65PVI1KM7:TR?= MVLTRW5IWkWU
MMAC-SF M3TLeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFyzPHpKSzVyPUSuNFI1PjdizszN Ml:5V2FPT1KHUh?=
NMC-G1 M2XlTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MojFTWM2OD12LkKyO|I{KM7:TR?= M{XCb3NCVkeURWK=
SW872 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXPJR|UxRTRwM{SzOEDPxE1? M1fq[nNCVkeURWK=
TE-12 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFHp[5lKSzVyPUSuOVY{QTRizszN MX;TRW5IWkWU
LU-139 NFTm[oZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4DjUGlEPTB;ND62NVg{PSEQvF2= NGjk[3dUSU6JUlXS
HC-1 M3TSSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{XKfmlEPTB;ND62PVQ6PCEQvF2= M4[1[nNCVkeURWK=
COR-L279 NYLCZmR2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHjjTGZKSzVyPUSuO|U5QTFizszN M{XxcXNCVkeURWK=
SF268 MlXmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{m4N2lEPTB;ND63PVkyPiEQvF2= NGDtd3BUSU6JUlXS
MC-CAR NVTvdoVtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlH2TWM2OD13LkC2O|U4KM7:TR?= MmfyV2FPT1KHUh?=
TK10 M{PuSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXrJWWtHUUN3ME21MlM2PDZ7IN88US=> MXPTRW5IWkWU
TE-1 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mm\nTWM2OD13LkS5NFA1KM7:TR?= M3XRdnNCVkeURWK=
NCI-H2126 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX3yW3llUUN3ME21MlY1PTd2IN88US=> NU\nfoE1W0GQR2LFVi=>
Daudi M2\UWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUf6OGZOUUN3ME21MlY6OTJizszN NUjUXldXW0GQR2LFVi=>
NCI-H1648 M3S2WGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4f6b2lEPTB;NT64NVQ2PCEQvF2= NHjVcJNUSU6JUlXS
OS-RC-2 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M372cmlEPTB;NT65PFU6PyEQvF2= M4\ZWnNCVkeURWK=
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LS-1034 MmPiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUjJR|UxRTZwN{W2OkDPxE1? MmXnV2FPT1KHUh?=
NCI-H1581 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NITGbpdKSzVyPU[uO|g1ODVizszN NXnJUHNNW0GQR2LFVi=>
UACC-257 M1m2R2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NILyblBKSzVyPUeuNFQ2OTJizszN MoT3V2FPT1KHUh?=
KM-H2 MmG0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV7s[2NjUUN3ME23MlE5PDV5IN88US=> M2XNRXNCVkeURWK=
NCI-H1436 NX\hOoYxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3G4O2lEPTB;Nz62PVk{OiEQvF2= MXHTRW5IWkWU
IA-LM MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M13vT2lEPTB;Nz64OVkh|ryP NV30OXRnW0GQR2LFVi=>
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GCIY MoTrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmjuTWM2OD16LkO2PVY2KM7:TR?= M1nEc3NCVkeURWK=
CP67-MEL MnPNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEO1[lVKSzVyPUiuOVMzPiEQvF2= NGe4W3FUSU6JUlXS
KALS-1 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MonQTWM2OD16LkizPFUyKM7:TR?= NXPIUWR[W0GQR2LFVi=>
NCI-H1770 Mo\xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX3JR|UxRThwOUCyOlUh|ryP NIK3O5FUSU6JUlXS
8-MG-BA NWO3SXBUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1nYTGlEPTB;OT6zNlg1PCEQvF2= M2TsT3NCVkeURWK=
KY821 NFS2RoNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1vXSmlEPTB;OT63O|Q5PCEQvF2= MmixV2FPT1KHUh?=
SNB75 NF\Hb5dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF3DSnRKSzVyPUGwMlA4PiEQvF2= NWXFWHpVW0GQR2LFVi=>
NCCIT M3HZOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{PSVWlEPTB;MUGuNFU5OiEQvF2= NIe3bpNUSU6JUlXS
SJSA-1 NHPRN3NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NULTNo15UUN3ME2xNU4zQDlzIN88US=> M3q3UHNCVkeURWK=
LB373-MEL-D MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1LDZmlEPTB;MUGuN|gzPyEQvF2= MnL0V2FPT1KHUh?=
TALL-1 M{LDT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEfTeFZKSzVyPUGxMlQxPThizszN MXXTRW5IWkWU
NB69 NHSwN2VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkLrTWM2OD1zMT63O|A2KM7:TR?= MlftV2FPT1KHUh?=
NCI-H1355 NVy2VY5mT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVLWVWp1UUN3ME2xNU46PDJ4IN88US=> NF7JW2dUSU6JUlXS
DMS-153 NHO0NodIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUXJR|UxRTF{LkC0NlYh|ryP M3PnXHNCVkeURWK=
OPM-2 MkXNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH3JN41KSzVyPUGyMlE2QTZizszN M2XwcnNCVkeURWK=
NB1 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWLJR|UxRTF{LkK5JO69VQ>? NV3yOmFHW0GQR2LFVi=>
A3-KAW NGrk[XNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVvJR|UxRTF{LkOyN|Yh|ryP NIP5[YpUSU6JUlXS
NCI-H1882 NEPjTZhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYXJR|UxRTF{LkSwOlYh|ryP MkjCV2FPT1KHUh?=
KG-1 MnL1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1\Wd2lEPTB;MUKuOlU1PSEQvF2= M{[4UHNCVkeURWK=
LC4-1 NG\YU|JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1j3XmlEPTB;MUKuO|cxPiEQvF2= MkXOV2FPT1KHUh?=
HCE-T MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIrkVVZKSzVyPUGzMlAxPDlizszN MYnTRW5IWkWU
NEC8 MmjPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYTJR|UxRTF|LkGwN|gh|ryP Mn\nV2FPT1KHUh?=
IST-MEL1 NGSzOJlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVKx[IRDUUN3ME2xN{42Pzh6IN88US=> NXqxfWhXW0GQR2LFVi=>
EW-3 NYGxfI02T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGjMbZlKSzVyPUGzMlc1ODJizszN M1\Je3NCVkeURWK=
CTB-1 MnLzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHfaTZVKSzVyPUG0MlA{OjlizszN NVPTNpJHW0GQR2LFVi=>
LS-123 NVrL[oI5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1K4UGlEPTB;MUSuNVU5QCEQvF2= NV3mXG5zW0GQR2LFVi=>
NCI-H1417 M{e4UWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoT0TWM2OD1zND6zNFUzKM7:TR?= NV\qNFlYW0GQR2LFVi=>
MZ7-mel NGH5UHlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFX5RVhKSzVyPUG0MlQ1OzNizszN MnK5V2FPT1KHUh?=
JiyoyeP-2003 NXH6bXVYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWLTNFFTUUN3ME2xOU43OzJ4IN88US=> MnnHV2FPT1KHUh?=
ES6 NW\GTHJFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlLnTWM2OD1zNj6yN|YyKM7:TR?= Moj3V2FPT1KHUh?=
HH MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWDJR|UxRTF5LkG5OlMh|ryP MVzTRW5IWkWU
SF539 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGP2SGxKSzVyPUG3Mlk6OjJizszN NH71cJRUSU6JUlXS
Calu-6 MlzmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVzaS|BqUUN3ME2xPU4zOzlizszN NUHxbXF{W0GQR2LFVi=>
SK-MM-2 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXjJR|UxRTF7LkW1OUDPxE1? MY\TRW5IWkWU
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GI-ME-N NFnIeldIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NW\rS4J3UUN3ME2xPU45OjJ5IN88US=> NYrMZmVxW0GQR2LFVi=>
CAL-148 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXPnbXAxUUN3ME2yNE46QTN2IN88US=> NE\yOW1USU6JUlXS
EVSA-T NWH5[5BsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{DPUWlEPTB;MkGuNVQ6QSEQvF2= NUPVXo9vW0GQR2LFVi=>
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BOKU MmjNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2rxSmlEPTB;MkGuOFU{OyEQvF2= NHnZXFFUSU6JUlXS
KLE MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{\tN2lEPTB;MkKuNVkxOyEQvF2= NWDHU5R[W0GQR2LFVi=>
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MPP-89 NYLrXGZKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3ezSWlEPTB;MkWuOVMyPCEQvF2= MXPTRW5IWkWU
no-11 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH7VWVJKSzVyPUK1Mlc1PyEQvF2= M2jsNnNCVkeURWK=
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TGBC1TKB M3;IdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEHiZY1KSzVyPUK3MlU2QDVizszN M2j1NXNCVkeURWK=
MHH-PREB-1 NIq4OVhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUnJR|UxRTJ6LkC3N|Qh|ryP Mk\4V2FPT1KHUh?=
MZ2-MEL M2XlXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEWx[nVKSzVyPUK4MlYyPDNizszN M{DofHNCVkeURWK=
U-266 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmKyTWM2OD1{OD62N|Y3KM7:TR?= MnXHV2FPT1KHUh?=
SNU-C1 NH7tXmVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYjSSWJRUUN3ME2yPE46PDNizszN M1jhfHNCVkeURWK=
SW962 NFr4dVVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVft[Ih1UUN3ME2zNE4zPzR5IN88US=> NU\IXWc1W0GQR2LFVi=>
Raji MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4LBc2lEPTB;M{CuOVU6OiEQvF2= M4K2bnNCVkeURWK=
KNS-42 NUTUPYtXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4HTU2lEPTB;M{CuPFk2PiEQvF2= MXrTRW5IWkWU
LB996-RCC MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHz1dFBKSzVyPUOxMlE4ODJizszN M1HDSnNCVkeURWK=
CHP-126 NYXUfXliT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkTqTWM2OD1|MT6xPVg1KM7:TR?= MVHTRW5IWkWU
RXF393 M3zqSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3vWU2lEPTB;M{KuOFk4KM7:TR?= M2LH[3NCVkeURWK=
COLO-684 MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{LM[GlEPTB;M{KuOlQ{QCEQvF2= MmPRV2FPT1KHUh?=
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TE-441-T MmrBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4fVT2lEPTB;M{SuOlM4OSEQvF2= M{fIfHNCVkeURWK=
HCC2157 M33FWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2nhfmlEPTB;M{WuOFYyQSEQvF2= NYmwb49UW0GQR2LFVi=>
ES3 M175RWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnLrTWM2OD1|Nj62O|Uh|ryP MnfVV2FPT1KHUh?=
NCI-H1155 NFi2NndIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MljPTWM2OD1|Nz64NVUh|ryP NHTMZVBUSU6JUlXS
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GDM-1 MoKxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn[5TWM2OD1|OD65NVE3KM7:TR?= Mk\UV2FPT1KHUh?=
KU812 NYK5SW8xT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4S5OWlEPTB;NEGuOVA4KM7:TR?= M1u5ZnNCVkeURWK=
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GI-1 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUXHZZJnUUN3ME20Nk46OTl{IN88US=> NYH0[XNqW0GQR2LFVi=>
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DG-75 NUXrN5E3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV31TlNFUUN3ME20OU4yPTd5IN88US=> MXzTRW5IWkWU
COR-L88 M1u4bGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX3JR|UxRTR3LkK3O|gh|ryP NVzuUHRMW0GQR2LFVi=>
LS-513 NIrlSoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M33HTWlEPTB;NEWuPVE2PiEQvF2= M1HBXHNCVkeURWK=
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L-363 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIjY[ZpKSzVyPUS2Mlg5OSEQvF2= NIH4TXBUSU6JUlXS
TE-6 NUXHUmt4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX;sbI9sUUN3ME20PE41PDZizszN MXjTRW5IWkWU
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TE-5 MnrVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1n2TWlEPTB;NEmuO|EyQCEQvF2= MV3TRW5IWkWU

... 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 slightly soluble or insoluble
Ethanol slightly soluble or insoluble
In vivo Add solvents individually and in order:
30% PEG400+0.5% Tween80+5% propylene glycol
30 mg/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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Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

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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

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID