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 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1;wOWlEPTB;MD6wNFM{QCEQvF2= NHzzWXFUSU6JUlXS
RS4-11 NIqzTGtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYLJR|UxRTBwMEC0NFQh|ryP NVy5Z5N4W0GQR2LFVi=>
MFH-ino NG\vUYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUnJR|UxRTBwMEC5PUDPxE1? NX7TT29MW0GQR2LFVi=>
NTERA-S-cl-D1 NHnaO2pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVXJR|UxRTBwMEG0N|Qh|ryP M2niVnNCVkeURWK=
697 NFmzdphIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{S4UGlEPTB;MD6wNlQ4OSEQvF2= M4\tcXNCVkeURWK=
NALM-6 NEiwUGJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2rTTGlEPTB;MD6wNlU2OiEQvF2= MojMV2FPT1KHUh?=
ES8 NIf2fXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2rnU2lEPTB;MD6wOFYyOyEQvF2= NF\WeVlUSU6JUlXS
HUTU-80 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUTHbGk4UUN3ME2wMlA2Ojl7IN88US=> NU\CSYFsW0GQR2LFVi=>
MV-4-11 NFS4T25Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX61foZ{UUN3ME2wMlA4Pzh{IN88US=> NGO3XpVUSU6JUlXS
MONO-MAC-6 M{i3Nmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1uwZ2lEPTB;MD6wO|g4QSEQvF2= Ml[5V2FPT1KHUh?=
LC-2-ad NYLERpNRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEjH[IFKSzVyPUCuNFg4QDlizszN NF\qSJdUSU6JUlXS
BL-41 NX7Id2t3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{XBWWlEPTB;MD6xNFQ1PSEQvF2= M1vvV3NCVkeURWK=
A4-Fuk NXvLVZhYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NITyPJRKSzVyPUCuNVE2PjNizszN NGnWOolUSU6JUlXS
SW954 M2XEe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH:wVWtKSzVyPUCuNVIzOjlizszN MXvTRW5IWkWU
BV-173 M{XVUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV3JR|UxRTBwMUK2OFEh|ryP MXfTRW5IWkWU
TE-11 NHLVO45Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1LDXWlEPTB;MD6xOFk5OiEQvF2= M1Ppe3NCVkeURWK=
SK-UT-1 MojMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYjG[HliUUN3ME2wMlE2QTZ3IN88US=> NGjzZ2xUSU6JUlXS
SIG-M5 NVfNN5dbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NILwZXVKSzVyPUCuNVY4ODdizszN M4fPcHNCVkeURWK=
OCUB-M M2rxN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWrJR|UxRTBwMU[5PFMh|ryP MkPnV2FPT1KHUh?=
K052 Mmm0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFXoclJKSzVyPUCuNVk1QCEQvF2= NH[xXIZUSU6JUlXS
VA-ES-BJ Mn7TS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXnJR|UxRTBwMkCwPFYh|ryP NHHGbopUSU6JUlXS
SW982 NGHpNYdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mm\wTWM2OD1yLkKxN|gh|ryP NUfRV4FWW0GQR2LFVi=>
LB647-SCLC NF33cI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVPJR|UxRTBwMkG1NlMh|ryP NUW0O3dZW0GQR2LFVi=>
PSN1 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MojUTWM2OD1yLkKyNFI3KM7:TR?= MYfTRW5IWkWU
BB30-HNC M1GxUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NITRdVhKSzVyPUCuNlI2QTFizszN MVzTRW5IWkWU
ST486 NI\qTlZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWnJR|UxRTBwMkOwPFch|ryP NULlcGFQW0GQR2LFVi=>
MOLT-4 Mn3MS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mo\iTWM2OD1yLkKzN|M4KM7:TR?= MoHiV2FPT1KHUh?=
EW-16 NWHYVGM6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXvS[WlnUUN3ME2wMlI{PzZ6IN88US=> MXXTRW5IWkWU
KS-1 Mnm0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUHJR|UxRTBwMkO3PFUh|ryP MlrnV2FPT1KHUh?=
SR NUD1NWJWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlrFTWM2OD1yLkK0OVY1KM7:TR?= NHHRS|NUSU6JUlXS
KM12 NXe1OXh1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVvSflU2UUN3ME2wMlI3OzZizszN MUHTRW5IWkWU
EM-2 M4fu[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NI\BeYpKSzVyPUCuNlY3PDFizszN MnnyV2FPT1KHUh?=
MEG-01 M3HYTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFXBW5lKSzVyPUCuNlc5PDlizszN M3ftd3NCVkeURWK=
NB13 MlzUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn\nTWM2OD1yLkK3PVg1KM7:TR?= NWHHbpB4W0GQR2LFVi=>
RKO NILDW4dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2\PVmlEPTB;MD6zNFgyOyEQvF2= NWTFN4Z2W0GQR2LFVi=>
CESS MkjWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MV7JR|UxRTBwM{GzNlgh|ryP NWfIVW16W0GQR2LFVi=>
EoL-1-cell NWLRZXhrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWPHV21WUUN3ME2wMlM{PDV7IN88US=> MmXQV2FPT1KHUh?=
DOHH-2 Moi4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXPBfnBwUUN3ME2wMlM{PzhzIN88US=> Mn3tV2FPT1KHUh?=
A388 NHXvWIJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXvJR|UxRTBwM{SwPFYh|ryP M4HnUXNCVkeURWK=
LAMA-84 NV;ZR|NXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHTHRlFKSzVyPUCuN|UyPzhizszN Mke5V2FPT1KHUh?=
IMR-5 MofFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWjycoNXUUN3ME2wMlM2PTRizszN NGP0eW9USU6JUlXS
KARPAS-422 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1izUmlEPTB;MD6zO|I4OiEQvF2= M{\oNXNCVkeURWK=
MRK-nu-1 NY\uUmZvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWrJR|UxRTBwM{ixN{DPxE1? MmTHV2FPT1KHUh?=
BL-70 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2H6XmlEPTB;MD6zPFk4PCEQvF2= NFSwXVFUSU6JUlXS
LXF-289 NUjaTJpWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUjmVnFXUUN3ME2wMlQxPDB4IN88US=> M4DjdnNCVkeURWK=
RL95-2 NVrqfoc5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYTJR|UxRTBwNEC1Olch|ryP NHLnZ3RUSU6JUlXS
QIMR-WIL NVzOUZlST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MonTTWM2OD1yLkSyOlc3KM7:TR?= MoTaV2FPT1KHUh?=
K-562 NIXqcodIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYDsdJhbUUN3ME2wMlQ{PDd{IN88US=> M2PXdnNCVkeURWK=
NCI-H510A M2fhXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIC0[oJKSzVyPUCuOFM5OjNizszN NVjuZVRmW0GQR2LFVi=>
NCI-H524 NHvWZ4dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXm3foZqUUN3ME2wMlUyOTR5IN88US=> MoD5V2FPT1KHUh?=
KE-37 NF\6bXFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVrXdFEzUUN3ME2wMlUzOTB{IN88US=> MlzOV2FPT1KHUh?=
KP-N-YS NHnrbo5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUnJR|UxRTBwNUSzPVIh|ryP Mom2V2FPT1KHUh?=
LS-411N MmPDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVPmeIl1UUN3ME2wMlU4PzV{IN88US=> NXXlNHoxW0GQR2LFVi=>
CTV-1 NVTFOHFQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1rhTWlEPTB;MD61PFc4OyEQvF2= NUDaPVJJW0GQR2LFVi=>
NCI-SNU-16 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NULTWnU3UUN3ME2wMlY{PTdzIN88US=> NETIRpVUSU6JUlXS
HT-144 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGH3VZZKSzVyPUCuOlM4QThizszN MkjaV2FPT1KHUh?=
NCI-H187 NXftNpZFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVLJR|UxRTBwNkSxN{DPxE1? M1Tt[3NCVkeURWK=
OCI-AML2 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NU\0eItVUUN3ME2wMlY1PDB|IN88US=> NG\z[oZUSU6JUlXS
CCRF-CEM M4HNUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYDJR|UxRTBwNkWzOFYh|ryP NFfPWphUSU6JUlXS
ONS-76 NV\jd|ZRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUHJR|UxRTBwNk[0OVgh|ryP NUXmd2pqW0GQR2LFVi=>
IST-SL2 Mn;MS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHPFXJJKSzVyPUCuO|E6QDJizszN NVjBNYlMW0GQR2LFVi=>
NB6 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFzLfoxKSzVyPUCuO|czPTRizszN NH7VUWpUSU6JUlXS
SK-PN-DW M{D4ZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3zBN2lEPTB;MD63PVE1KM7:TR?= NGL6eHhUSU6JUlXS
HCC1599 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{jTZWlEPTB;MD64NFg4PCEQvF2= NVnBW2NVW0GQR2LFVi=>
MC116 NIrBPGlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4WxXmlEPTB;MD64OVAyOSEQvF2= MYTTRW5IWkWU
TE-15 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYHJR|UxRTBwOEWwPVgh|ryP NWX0XGFKW0GQR2LFVi=>
HOP-62 NYXVUFgyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MknyTWM2OD1yLki2N|I6KM7:TR?= NHHJb2lUSU6JUlXS
TGBC24TKB MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MW\JR|UxRTBwOE[zPFUh|ryP M1W3S3NCVkeURWK=
HCE-4 M2ntTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV[4OVhGUUN3ME2wMlg5ODZ|IN88US=> MVjTRW5IWkWU
ALL-PO NIi5NI9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWDW[o97UUN3ME2wMlg5OTd3IN88US=> M2DEZnNCVkeURWK=
KGN Mk\KS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYH4c4h3UUN3ME2wMlg6QTl3IN88US=> M4LNU3NCVkeURWK=
ML-2 M1;FNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3P0W2lEPTB;MD65NFI2QSEQvF2= NHfNZVJUSU6JUlXS
ES4 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVXSOnNqUUN3ME2wMlkyOTJ6IN88US=> M4Pq[nNCVkeURWK=
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DU-4475 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmC3TWM2OD1zLkCxO|U3KM7:TR?= MojtV2FPT1KHUh?=
NKM-1 NXzGVm9[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUDrSIFSUUN3ME2xMlAzPzd3IN88US=> NYLod2t5W0GQR2LFVi=>
HL-60 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHn5eVhKSzVyPUGuNFY2PzRizszN NYPyOpVZW0GQR2LFVi=>
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TE-10 Mn\QS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoP4TWM2OD1zLkGyPVQ3KM7:TR?= MkXrV2FPT1KHUh?=
ETK-1 Mm\vS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXe1SlRoUUN3ME2xMlE{PjF|IN88US=> MnjJV2FPT1KHUh?=
HAL-01 NV;jVYpHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUjJR|UxRTFwMU[3NFkh|ryP NH\uVnZUSU6JUlXS
BB65-RCC NY[z[XNHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGfFUIxKSzVyPUGuNVgxODVizszN MVHTRW5IWkWU
EW-1 M4rZbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWrDUYVHUUN3ME2xMlE5PTZ{IN88US=> MVjTRW5IWkWU
SK-NEP-1 NYe2THo4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX;Rb3ZCUUN3ME2xMlIyOTFzIN88US=> MkjoV2FPT1KHUh?=
SK-LMS-1 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmGzTWM2OD1zLkKyNlEzKM7:TR?= MWTTRW5IWkWU
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NCI-H1963 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NI\oRWlKSzVyPUGuO|A2QDNizszN MnLJV2FPT1KHUh?=
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TE-8 NVOwcIROT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGrsdldKSzVyPUGuPFA{PjhizszN NW\Ud5lvW0GQR2LFVi=>
NCI-H1304 NXLKRXRiT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3\HTmlEPTB;MT64N|A4OyEQvF2= M1zESXNCVkeURWK=
A101D M2HD[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUnJR|UxRTFwOEezPVUh|ryP NVzFN5ZwW0GQR2LFVi=>
SCLC-21H NVf5coh{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYTJR|UxRTFwOUewOVch|ryP NVO3SG94W0GQR2LFVi=>
GB-1 NEC4[|RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWfaZnU3UUN3ME2yMlAyPjR5IN88US=> Mn;aV2FPT1KHUh?=
KARPAS-45 MmC1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlTHTWM2OD1{LkCyOlU1KM7:TR?= MonVV2FPT1KHUh?=
ATN-1 Mk\zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnrDTWM2OD1{LkCyPFU5KM7:TR?= M3vxNXNCVkeURWK=
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RPMI-6666 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3PSRmlEPTB;Mj6xOlIxPyEQvF2= MnnEV2FPT1KHUh?=
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OVCAR-4 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWS3d5NjUUN3ME2yMlQ3OTNizszN Mn75V2FPT1KHUh?=
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NCI-H2107 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1TMSmlEPTB;Mj64N|cyOSEQvF2= M3nGeHNCVkeURWK=
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LB1047-RCC NEKxOWFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYnqfGtjUUN3ME2yMlg5OTJ4IN88US=> NXqxSJdRW0GQR2LFVi=>
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NCI-H209 NWHIbXMzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXzzcpZQUUN3ME2yMlkyOjV|IN88US=> MUXTRW5IWkWU
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RH-1 NVrLeWVqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NI\lXYtKSzVyPUOuNVczQTFizszN Mn3TV2FPT1KHUh?=
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TE-9 Ml6zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mk\PTWM2OD1|LkK2O|M3KM7:TR?= NUToZnJsW0GQR2LFVi=>
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RPMI-8402 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1izOWlEPTB;Mz61PFYxOyEQvF2= MVPTRW5IWkWU
HEL Mo\YS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnnxTWM2OD1|Lk[zNkDPxE1? MknNV2FPT1KHUh?=
NOS-1 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mon1TWM2OD1|Lki0O|U1KM7:TR?= NGrK[2ZUSU6JUlXS
ES1 NG\0XIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH7oeZNKSzVyPUOuPVIzQTNizszN NWrIOVY4W0GQR2LFVi=>
NCI-H2171 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIi3[5VKSzVyPUOuPVI1OjNizszN NYfrSoZlW0GQR2LFVi=>
NCI-H747 NFjyNYNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnPGTWM2OD1|Lkm0NlIyKM7:TR?= MXLTRW5IWkWU
MHH-NB-11 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYjJR|UxRTNwOUWzNVIh|ryP MofOV2FPT1KHUh?=
MZ1-PC NIPlU49Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmDTTWM2OD1|Lkm5NlQh|ryP MYTTRW5IWkWU
MMAC-SF NYLVdo9vT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYDBRlFGUUN3ME20MlAzPDZ5IN88US=> MlHnV2FPT1KHUh?=
NMC-G1 M2Lt[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWnQWmdLUUN3ME20MlIzPzJ|IN88US=> M{ju[HNCVkeURWK=
SW872 NIrZUZJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX3JR|UxRTRwM{SzOEDPxE1? NVvSdnVUW0GQR2LFVi=>
TE-12 MoewS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXrJR|UxRTRwNU[zPVQh|ryP NU\ZTGtSW0GQR2LFVi=>
LU-139 NUXFPY14T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGHwOmJKSzVyPUSuOlE5OzVizszN M3n4NnNCVkeURWK=
HC-1 MlzXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXzBc4pbUUN3ME20MlY6PDl2IN88US=> MYPTRW5IWkWU
COR-L279 NYfjb4s4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHnjTW9KSzVyPUSuO|U5QTFizszN NYXHb2xQW0GQR2LFVi=>
SF268 M2HieWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWXJR|UxRTRwN{m5NVYh|ryP M1S3PXNCVkeURWK=
MC-CAR M3PQXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3zmcGlEPTB;NT6wOlc2PyEQvF2= M{GxUXNCVkeURWK=
TK10 MlPaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUTYO2NnUUN3ME21MlM2PDZ7IN88US=> MmHPV2FPT1KHUh?=
TE-1 M3[xTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUfFT29DUUN3ME21MlQ6ODB2IN88US=> Mm\IV2FPT1KHUh?=
NCI-H2126 MmP5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHnKNW1KSzVyPUWuOlQ2PzRizszN M2Hle3NCVkeURWK=
Daudi NHrJd41Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEfzT5FKSzVyPUWuOlkyOiEQvF2= NX;2R41yW0GQR2LFVi=>
NCI-H1648 NVvBR4pwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkHITWM2OD13LkixOFU1KM7:TR?= MnrSV2FPT1KHUh?=
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DJM-1 MoKzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYrVVmEyUUN3ME22MlM1PjZ4IN88US=> MYnTRW5IWkWU
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NCI-H1581 Mnr1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmezTWM2OD14Lke4OFA2KM7:TR?= MWrTRW5IWkWU
UACC-257 NX;GWIRlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2rGZ2lEPTB;Nz6wOFUyOiEQvF2= MXzTRW5IWkWU
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NCI-H1436 MkfBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{LqcWlEPTB;Nz62PVk{OiEQvF2= Mmi0V2FPT1KHUh?=
IA-LM Mmf5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUPJR|UxRTdwOEW5JO69VQ>? MUjTRW5IWkWU
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TALL-1 MlfiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWr3S3V[UUN3ME2xNU41ODV6IN88US=> M{XzZXNCVkeURWK=
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DMS-153 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlPSTWM2OD1zMj6wOFI3KM7:TR?= MoHrV2FPT1KHUh?=
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NB1 MlzlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnLjTWM2OD1zMj6yPUDPxE1? M4nKWXNCVkeURWK=
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NCI-H1882 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4nibWlEPTB;MUKuOFA3PiEQvF2= MX3TRW5IWkWU
KG-1 MoPzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnK5TWM2OD1zMj62OVQ2KM7:TR?= NHfmR3JUSU6JUlXS
LC4-1 M3fJTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXTCdY9{UUN3ME2xNk44PzB4IN88US=> NYq3NWF1W0GQR2LFVi=>
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NEC8 MlP6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn;WTWM2OD1zMz6xNFM5KM7:TR?= NIPSXXhUSU6JUlXS
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EW-3 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUfiVpd1UUN3ME2xN{44PDB{IN88US=> NVHheZMxW0GQR2LFVi=>
CTB-1 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mnf3TWM2OD1zND6wN|I6KM7:TR?= Mnm5V2FPT1KHUh?=
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NCI-H1417 M{TiU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MonQTWM2OD1zND6zNFUzKM7:TR?= MlLWV2FPT1KHUh?=
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SF539 M3vNV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{nCUGlEPTB;MUeuPVkzOiEQvF2= NYjZ[5hyW0GQR2LFVi=>
Calu-6 NX;GcJlkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUPRS2k5UUN3ME2xPU4zOzlizszN Ml3lV2FPT1KHUh?=
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GI-ME-N NVj0TXQ5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{mwU2lEPTB;MUmuPFIzPyEQvF2= NUj6RYh4W0GQR2LFVi=>
CAL-148 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnLmTWM2OD1{MD65PVM1KM7:TR?= MmrCV2FPT1KHUh?=
EVSA-T MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFPiO4JKSzVyPUKxMlE1QTlizszN MlTVV2FPT1KHUh?=
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LB831-BLC M4Lkd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWS0NG92UUN3ME2yOU4yPTJ4IN88US=> MlzVV2FPT1KHUh?=
NCI-H889 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV7JR|UxRTJ3LkG5N|Eh|ryP M{PQenNCVkeURWK=
REH MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFH4WY9KSzVyPUK1MlQ3PzFizszN MVnTRW5IWkWU
KP-N-RT-BM-1 NEW2d3pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWnkcFJYUUN3ME2yOU41PzV{IN88US=> M4DkcHNCVkeURWK=
MPP-89 NXv1d2NyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXXi[3NPUUN3ME2yOU42OzF2IN88US=> MmTRV2FPT1KHUh?=
no-11 NGrwO2JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{XDcWlEPTB;MkWuO|Q4KM7:TR?= NV:4R|FwW0GQR2LFVi=>
NCI-H748 NYflcVQ{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4fKeWlEPTB;MkWuO|YzPyEQvF2= MULTRW5IWkWU
LB2518-MEL NVnNPZFoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlPCTWM2OD1{Nz6xO|c{KM7:TR?= MXjTRW5IWkWU
TGBC1TKB NXnnSI5NT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVjJR|UxRTJ5LkW1PFUh|ryP MoCwV2FPT1KHUh?=
MHH-PREB-1 M1;ySmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVr4e2JoUUN3ME2yPE4xPzN2IN88US=> NVzFfWk2W0GQR2LFVi=>
MZ2-MEL NUHkc2l{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEfHXFRKSzVyPUK4MlYyPDNizszN NUnEbpppW0GQR2LFVi=>
U-266 NVLo[mZnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVvJR|UxRTJ6Lk[zOlYh|ryP MnvZV2FPT1KHUh?=
SNU-C1 MVjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3TJdGlEPTB;MkiuPVQ{KM7:TR?= NXHi[FV1W0GQR2LFVi=>
SW962 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX3wTJZkUUN3ME2zNE4zPzR5IN88US=> M3HZeHNCVkeURWK=
Raji MnTpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIW1fGVKSzVyPUOwMlU2QTJizszN NH3rNFZUSU6JUlXS
KNS-42 MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MonkTWM2OD1|MD64PVU3KM7:TR?= NWK4OHhGW0GQR2LFVi=>
LB996-RCC NIDRboVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVzpPWdOUUN3ME2zNU4yPzB{IN88US=> NED1UndUSU6JUlXS
CHP-126 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUTJR|UxRTNzLkG5PFQh|ryP M33BNHNCVkeURWK=
RXF393 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYjJR|UxRTN{LkS5O{DPxE1? MoXCV2FPT1KHUh?=
COLO-684 NETGTZFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3P0W2lEPTB;M{KuOlQ{QCEQvF2= MWPTRW5IWkWU
A704 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUHmd3JvUUN3ME2zN{42PTN6IN88US=> NYDj[o5rW0GQR2LFVi=>
A253 NELSWWhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1S4V2lEPTB;M{OuOVg2OiEQvF2= NF\DUIVUSU6JUlXS
KNS-81-FD MlrQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4HKcWlEPTB;M{SuOVQ2PiEQvF2= M1n6ZnNCVkeURWK=
TE-441-T MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1u3WGlEPTB;M{SuOlM4OSEQvF2= MXXTRW5IWkWU
HCC2157 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlP3TWM2OD1|NT60OlE6KM7:TR?= NEL0SHZUSU6JUlXS
ES3 NFzPflNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MULJR|UxRTN4Lk[3OUDPxE1? NIHuRYdUSU6JUlXS
NCI-H1155 NITtb|lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEPlSWdKSzVyPUO3MlgyPSEQvF2= NVSwUYpwW0GQR2LFVi=>
SNU-C2B M1r4SWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEDtdXlKSzVyPUO4MlE3PTRizszN NVj1d|kzW0GQR2LFVi=>
JAR MnrDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUO5fWsxUUN3ME2zPE4zPDR7IN88US=> Mk\1V2FPT1KHUh?=
GDM-1 NXfCR2I{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2HCVmlEPTB;M{iuPVEyPiEQvF2= MVXTRW5IWkWU
KU812 MlLSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NE\Sfm1KSzVyPUSxMlUxPyEQvF2= MWDTRW5IWkWU
BC-1 M4jG[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX;JR|UxRTR{Lk[3N|Eh|ryP MVrTRW5IWkWU
GI-1 M1rKV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmPmTWM2OD12Mj65NVkzKM7:TR?= Ml;zV2FPT1KHUh?=
NCI-H1694 NGnaXmRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHrrO4dKSzVyPUS0Mlk1PzJizszN NGLYW|lUSU6JUlXS
DG-75 MoXDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1TF[WlEPTB;NEWuNVU4PyEQvF2= NUXXZXlFW0GQR2LFVi=>
COR-L88 NUXmcHZLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn;UTWM2OD12NT6yO|c5KM7:TR?= MXHTRW5IWkWU
LS-513 M3\0e2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV\RTI9iUUN3ME20OU46OTV4IN88US=> M2D2O3NCVkeURWK=
HD-MY-Z NHvDNFZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUjJR|UxRTR4LkS2NVIh|ryP MlSxV2FPT1KHUh?=
L-363 NYf4W5o{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGDQ[YJKSzVyPUS2Mlg5OSEQvF2= MXrTRW5IWkWU
TE-6 NGj1TmVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVjISlM4UUN3ME20PE41PDZizszN MXTTRW5IWkWU
NCI-H345 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmrXTWM2OD12OD60Olgh|ryP NVy0RWhZW0GQR2LFVi=>
TE-5 NVHoTG5qT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2fj[mlEPTB;NEmuO|EyQCEQvF2= M{H1R3NCVkeURWK=

... 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:
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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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

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