VX-680 (Tozasertib, MK-0457)

Catalog No.S1048

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

Molecular Weight(MW): 464.59

VX-680 (Tozasertib, 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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In DMSO USD 134 In stock
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USD 370 In stock
USD 470 In stock

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Cited by 35 Publications

15 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. VX-680 (Tozasertib, 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. VX-680 (Tozasertib, 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. VX-680 (Tozasertib, 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. VX-680 (Tozasertib, 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. VX-680 (Tozasertib, 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. VX-680 (Tozasertib, 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. VX-680 (Tozasertib, 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. VX-680 (Tozasertib, 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. VX-680 (Tozasertib, 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. VX-680 (Tozasertib, 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. VX-680 (Tozasertib, 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. VX-680 (Tozasertib, 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. VX-680 (Tozasertib, 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. VX-680 (Tozasertib, MK-0457) purchased from Selleck.

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

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

Purity & Quality Control

Choose Selective Aurora Kinase Inhibitors

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Notes:

2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

Biological Activity

Description VX-680 (Tozasertib, 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 M1\ReGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYPJR|UxRTBwMECzN|gh|ryP NF\IS|dUSU6JUlXS
RS4-11 MoHtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NETweFRKSzVyPUCuNFA1ODRizszN Mn;PV2FPT1KHUh?=
MFH-ino M{W5U2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV7JR|UxRTBwMEC5PUDPxE1? MVzTRW5IWkWU
NTERA-S-cl-D1 M2HtV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlfNTWM2OD1yLkCxOFM1KM7:TR?= MYTTRW5IWkWU
697 MlrOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGruToFKSzVyPUCuNFI1PzFizszN NIi5eGhUSU6JUlXS
NALM-6 NXTqT29rT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH65eItKSzVyPUCuNFI2PTJizszN M4O5U3NCVkeURWK=
ES8 MnzwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkPRTWM2OD1yLkC0OlE{KM7:TR?= MYjTRW5IWkWU
HUTU-80 NGXHcYZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlrtTWM2OD1yLkC1Nlk6KM7:TR?= M1jqenNCVkeURWK=
MV-4-11 NHrkVG9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NW\WUWdDUUN3ME2wMlA4Pzh{IN88US=> MkHyV2FPT1KHUh?=
MONO-MAC-6 NYHONmV[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4jZWWlEPTB;MD6wO|g4QSEQvF2= M1;YTHNCVkeURWK=
LC-2-ad NF7iXohIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYHJR|UxRTBwMEi3PFkh|ryP NV7ldWJNW0GQR2LFVi=>
BL-41 MlnMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWXJR|UxRTBwMUC0OFUh|ryP M2LmZ3NCVkeURWK=
A4-Fuk Mn[4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{\2fWlEPTB;MD6xNVU3OyEQvF2= M3fL[3NCVkeURWK=
SW954 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH;KVYFKSzVyPUCuNVIzOjlizszN NX71XolYW0GQR2LFVi=>
BV-173 M2H1Z2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mo\oTWM2OD1yLkGyOlQyKM7:TR?= NInvcFFUSU6JUlXS
TE-11 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXLJR|UxRTBwMUS5PFIh|ryP Mkn4V2FPT1KHUh?=
SK-UT-1 NUHFN5pMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV3XXZBnUUN3ME2wMlE2QTZ3IN88US=> MlHaV2FPT1KHUh?=
SIG-M5 NV[0cYZ5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml7aTWM2OD1yLkG2O|A4KM7:TR?= M1zISnNCVkeURWK=
OCUB-M M2LBPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1\NfGlEPTB;MD6xOlk5OyEQvF2= MVrTRW5IWkWU
K052 MorUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXjrbFh1UUN3ME2wMlE6PDhizszN M{PI[HNCVkeURWK=
VA-ES-BJ NX33TpVIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2i1fWlEPTB;MD6yNFA5PiEQvF2= NWqwem1{W0GQR2LFVi=>
SW982 M3jLWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2O4PGlEPTB;MD6yNVM5KM7:TR?= NVTJSYFTW0GQR2LFVi=>
LB647-SCLC M4XNeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoLKTWM2OD1yLkKxOVI{KM7:TR?= MlvZV2FPT1KHUh?=
PSN1 M1TTZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVGyOmFMUUN3ME2wMlIzODJ4IN88US=> NIXPfFlUSU6JUlXS
BB30-HNC NE\lSlBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHe5e2pKSzVyPUCuNlI2QTFizszN MnjXV2FPT1KHUh?=
ST486 MoXZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFnQOYdKSzVyPUCuNlMxQDdizszN M{m0R3NCVkeURWK=
MOLT-4 M4DWR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVTnTnNnUUN3ME2wMlI{OzN5IN88US=> M1T4WHNCVkeURWK=
EW-16 NGLuTHVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGTFVFBKSzVyPUCuNlM4PjhizszN NYDGT|ZUW0GQR2LFVi=>
KS-1 M1\hWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnTpTWM2OD1yLkKzO|g2KM7:TR?= M3;lUXNCVkeURWK=
SR NUfzZodJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFGwcVFKSzVyPUCuNlQ2PjRizszN M3vre3NCVkeURWK=
KM12 NWnxSG8xT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVLJR|UxRTBwMk[zOkDPxE1? MmHXV2FPT1KHUh?=
EM-2 MoXQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mk\hTWM2OD1yLkK2OlQyKM7:TR?= MljMV2FPT1KHUh?=
MEG-01 Ml;iS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2jKcWlEPTB;MD6yO|g1QSEQvF2= MYrTRW5IWkWU
NB13 NYjrVYpPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX[yXIFlUUN3ME2wMlI4QTh2IN88US=> NXmyWFE3W0GQR2LFVi=>
RKO NFW0dplIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEHBUXBKSzVyPUCuN|A5OTNizszN NV3rZYRSW0GQR2LFVi=>
CESS M2Hxfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlzETWM2OD1yLkOxN|I5KM7:TR?= NEPyTZlUSU6JUlXS
EoL-1-cell M37o[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4nRb2lEPTB;MD6zN|Q2QSEQvF2= NX3TU2NOW0GQR2LFVi=>
DOHH-2 M3P1WGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXrJR|UxRTBwM{O3PFEh|ryP NF;EPYhUSU6JUlXS
A388 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlW1TWM2OD1yLkO0NFg3KM7:TR?= MVLTRW5IWkWU
LAMA-84 M1:2WGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV\JR|UxRTBwM{WxO|gh|ryP NEO5OGpUSU6JUlXS
IMR-5 NVfxb4RzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MY\JR|UxRTBwM{W1OEDPxE1? M1PBWnNCVkeURWK=
KARPAS-422 NGLrZlVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkfyTWM2OD1yLkO3NlczKM7:TR?= M3SzN3NCVkeURWK=
MRK-nu-1 NWDLV41lT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2P5c2lEPTB;MD6zPFE{KM7:TR?= NFn6dYVUSU6JUlXS
BL-70 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFrZVFJKSzVyPUCuN|g6PzRizszN M1m5R3NCVkeURWK=
LXF-289 NF\Y[WVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGDrXZJKSzVyPUCuOFA1ODZizszN MlfzV2FPT1KHUh?=
RL95-2 MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIn1[W5KSzVyPUCuOFA2PjdizszN NVT4T5ozW0GQR2LFVi=>
QIMR-WIL MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIr6SXNKSzVyPUCuOFI3PzZizszN M3vN[3NCVkeURWK=
K-562 NG\nZVdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MY\JR|UxRTBwNEO0O|Ih|ryP NGnGZmRUSU6JUlXS
NCI-H510A NVX5XnV7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MorGTWM2OD1yLkSzPFI{KM7:TR?= NGnxcnlUSU6JUlXS
NCI-H524 NGXTR2JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnjqTWM2OD1yLkWxNVQ4KM7:TR?= NUXme3ZYW0GQR2LFVi=>
KE-37 NGrDOFNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml;4TWM2OD1yLkWyNVAzKM7:TR?= MYnTRW5IWkWU
KP-N-YS NH\NOHhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MofKTWM2OD1yLkW0N|kzKM7:TR?= M2XudXNCVkeURWK=
LS-411N Ml7pS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWXJR|UxRTBwNUe3OVIh|ryP M4O2UHNCVkeURWK=
CTV-1 NHHSSlJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWjJR|UxRTBwNUi3O|Mh|ryP MnvjV2FPT1KHUh?=
NCI-SNU-16 NWjT[ZlvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEjNU2FKSzVyPUCuOlM2PzFizszN NWfacG9LW0GQR2LFVi=>
HT-144 MnrlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkPKTWM2OD1yLk[zO|k5KM7:TR?= NX7VSnRuW0GQR2LFVi=>
NCI-H187 MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlPLTWM2OD1yLk[0NVMh|ryP MYfTRW5IWkWU
OCI-AML2 NGPoc5ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3L6N2lEPTB;MD62OFQxOyEQvF2= MmnZV2FPT1KHUh?=
CCRF-CEM MoDSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2T0NWlEPTB;MD62OVM1PiEQvF2= M2LzW3NCVkeURWK=
ONS-76 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnrwTWM2OD1yLk[2OFU5KM7:TR?= NFnMV|dUSU6JUlXS
IST-SL2 NYDCNmg2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnnNTWM2OD1yLkexPVgzKM7:TR?= NYqwVYpkW0GQR2LFVi=>
NB6 NWTiR4dqT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWPJR|UxRTBwN{eyOVQh|ryP M{XOZ3NCVkeURWK=
SK-PN-DW NY\POGJCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUTJR|UxRTBwN{mxOEDPxE1? MVHTRW5IWkWU
HCC1599 M2HvUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFvicnlKSzVyPUCuPFA5PzRizszN NV\tN5VsW0GQR2LFVi=>
MC116 MmS0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEfPfW5KSzVyPUCuPFUxOTFizszN MVLTRW5IWkWU
TE-15 NWLmW4ZST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFzaT|lKSzVyPUCuPFUxQThizszN MWnTRW5IWkWU
HOP-62 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1flNmlEPTB;MD64OlMzQSEQvF2= NX;2cZZFW0GQR2LFVi=>
TGBC24TKB MlOzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWfUNoFGUUN3ME2wMlg3Ozh3IN88US=> Mnn5V2FPT1KHUh?=
HCE-4 NU\CbFVbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUT1UHFlUUN3ME2wMlg5ODZ|IN88US=> NUn3d5N6W0GQR2LFVi=>
ALL-PO MoHaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{ewd2lEPTB;MD64PFE4PSEQvF2= NEnPTlZUSU6JUlXS
KGN NXrhb4FJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4q2PGlEPTB;MD64PVk6PSEQvF2= NGfJe4JUSU6JUlXS
ML-2 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUi5SZdyUUN3ME2wMlkxOjV7IN88US=> NHHHZYtUSU6JUlXS
ES4 NWHpd3hQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHfTSG5KSzVyPUCuPVEyOjhizszN MVXTRW5IWkWU
SF126 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF3o[lZKSzVyPUCuPVQ5OTlizszN M4TyTXNCVkeURWK=
SK-N-DZ NXvGdmZUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWWzd4c{UUN3ME2wMlk3OTh7IN88US=> MlLFV2FPT1KHUh?=
HCC1187 NEXvN3ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEXBTnlKSzVyPUGuNFA2ODVizszN NEi1eG9USU6JUlXS
DU-4475 NULWbIJbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWTTcVE2UUN3ME2xMlAyPzV4IN88US=> MUPTRW5IWkWU
NKM-1 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFTPSIZKSzVyPUGuNFI4PzVizszN NIqwUWhUSU6JUlXS
HL-60 NGraTGlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2fRbmlEPTB;MT6wOlU4PCEQvF2= MnvZV2FPT1KHUh?=
SBC-1 NYH3ZZEzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIXlWm9KSzVyPUGuNVI2PDJizszN MofaV2FPT1KHUh?=
TE-10 NFH2UFhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV7RfY5iUUN3ME2xMlEzQTR4IN88US=> MkPmV2FPT1KHUh?=
ETK-1 M3vQUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn7FTWM2OD1zLkGzOlE{KM7:TR?= NG\ZXHZUSU6JUlXS
HAL-01 NX3XcpMyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXG2To9OUUN3ME2xMlE3PzB7IN88US=> Mn:0V2FPT1KHUh?=
BB65-RCC MkLlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1y0bWlEPTB;MT6xPFAxPSEQvF2= NXHLSI1kW0GQR2LFVi=>
EW-1 M2LCR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUjJR|UxRTFwMUi1OlIh|ryP M2\BVHNCVkeURWK=
SK-NEP-1 M2G1U2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3fTTmlEPTB;MT6yNVEyOSEQvF2= NV7sWVY6W0GQR2LFVi=>
SK-LMS-1 NX\sZWZHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXjJR|UxRTFwMkKyNVIh|ryP NVH5XIdPW0GQR2LFVi=>
DEL MlXPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUXJR|UxRTFwMkW2OFMh|ryP MoThV2FPT1KHUh?=
GT3TKB Mn6xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn\6TWM2OD1zLkK4NFU4KM7:TR?= MWXTRW5IWkWU
MOLT-16 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHPHW5hKSzVyPUGuN|U1ODVizszN NGrlVZdUSU6JUlXS
CMK M4rPNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml\iTWM2OD1zLkSyNVE4KM7:TR?= MmLTV2FPT1KHUh?=
NB5 NGS4OHBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmTnTWM2OD1zLk[0NlI6KM7:TR?= NWLrU5ZDW0GQR2LFVi=>
NCI-H1963 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUP2UYw5UUN3ME2xMlcxPTh|IN88US=> NILacGhUSU6JUlXS
KURAMOCHI NHP5WZVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVXJR|UxRTFwN{i5NVEh|ryP M3r4OHNCVkeURWK=
TE-8 NH3Kb4tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoLWTWM2OD1zLkiwN|Y5KM7:TR?= MXrTRW5IWkWU
NCI-H1304 NWjSWmVPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGrYbVNKSzVyPUGuPFMxPzNizszN M{XUPXNCVkeURWK=
A101D MkPUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVzDe45RUUN3ME2xMlg4Ozl3IN88US=> NWLw[pFHW0GQR2LFVi=>
SCLC-21H MmLIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIHWVolKSzVyPUGuPVcxPTdizszN NH6zR2tUSU6JUlXS
GB-1 MoW0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXqxbYU6UUN3ME2yMlAyPjR5IN88US=> MXLTRW5IWkWU
KARPAS-45 Mmf1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXzJR|UxRTJwMEK2OVQh|ryP M1vWWXNCVkeURWK=
ATN-1 NFf2eVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NF7iRXFKSzVyPUKuNFI5PThizszN M{ixWHNCVkeURWK=
NCI-H720 MoD0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MULJR|UxRTJwME[yOFQh|ryP MkXlV2FPT1KHUh?=
RPMI-6666 MnXOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{K2VmlEPTB;Mj6xOlIxPyEQvF2= M3:0dXNCVkeURWK=
NB17 Moe2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1XCfWlEPTB;Mj6yPVI4KM7:TR?= M2LXdXNCVkeURWK=
IST-SL1 NGPH[I1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVPJR|UxRTJwMkm3OlUh|ryP MWTTRW5IWkWU
SH-4 MlTGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUnPdVFuUUN3ME2yMlMzPDZ7IN88US=> M{nLVXNCVkeURWK=
K5 NFLJd2NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXz4eZo4UUN3ME2yMlQxOzF7IN88US=> MkPYV2FPT1KHUh?=
OVCAR-4 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWn1TZhSUUN3ME2yMlQ3OTNizszN MmPuV2FPT1KHUh?=
ACN MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3X0RWlEPTB;Mj61NFIyOyEQvF2= NETIS45USU6JUlXS
TGW M{\QNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4PyZmlEPTB;Mj62OVg{OiEQvF2= NX;P[|NRW0GQR2LFVi=>
NCI-H2107 NHfITGtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWXJR|UxRTJwOEO3NVEh|ryP MWXTRW5IWkWU
NCI-H82 MoTHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF7OeolKSzVyPUKuPFM5OzhizszN NYD2c5JmW0GQR2LFVi=>
SK-N-FI NHS4RlJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3zibmlEPTB;Mj64Olg3QCEQvF2= NXPPOGJ6W0GQR2LFVi=>
LB1047-RCC NWf3S|lJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF\lW|RKSzVyPUKuPFgyOjZizszN NF75WHVUSU6JUlXS
LU-134-A M2S1Tmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVPJR|UxRTJwOEmyOkDPxE1? M3G4ZXNCVkeURWK=
NCI-H209 M{fGVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUTJR|UxRTJwOUGyOVMh|ryP NHTuS2VUSU6JUlXS
NOMO-1 NYHBS21zT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFviO3FKSzVyPUOuNFIzPzRizszN NYfmdoE3W0GQR2LFVi=>
RH-1 NH\pRWRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVnxWmxbUUN3ME2zMlE4OjlzIN88US=> NEPUN5FUSU6JUlXS
LOUCY MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUDOOpdPUUN3ME2zMlE5Pjl|IN88US=> NEe0dVdUSU6JUlXS
TE-9 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWLaU2YxUUN3ME2zMlI3PzN4IN88US=> NGDJNmNUSU6JUlXS
PF-382 MkTHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYfNWo1pUUN3ME2zMlM2Pzd6IN88US=> NIfodnRUSU6JUlXS
RPMI-8402 NXP5bZN2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHzpSFdKSzVyPUOuOVg3ODNizszN MX3TRW5IWkWU
HEL NIXaWnZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVf2SppwUUN3ME2zMlY{OiEQvF2= M2P4cHNCVkeURWK=
NOS-1 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnfJTWM2OD1|Lki0O|U1KM7:TR?= MlThV2FPT1KHUh?=
ES1 NUnwNHBwT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2\GUWlEPTB;Mz65NlI6OyEQvF2= M4\iTXNCVkeURWK=
NCI-H2171 NHP4PJhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MluxTWM2OD1|LkmyOFI{KM7:TR?= NYe4[mc1W0GQR2LFVi=>
NCI-H747 M{LN[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYXJR|UxRTNwOUSyNlEh|ryP NVTVS5BFW0GQR2LFVi=>
MHH-NB-11 NHS4dFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NW\w[lVMUUN3ME2zMlk2OzF{IN88US=> MXfTRW5IWkWU
MZ1-PC MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGnycHBKSzVyPUOuPVkzPCEQvF2= MX\TRW5IWkWU
MMAC-SF M1zHd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1rSemlEPTB;ND6wNlQ3PyEQvF2= NULONldUW0GQR2LFVi=>
NMC-G1 NH3PWHRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{PkO2lEPTB;ND6yNlczOyEQvF2= NXP3OIZyW0GQR2LFVi=>
SW872 NGLlZYpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFjEW2JKSzVyPUSuN|Q{PCEQvF2= NWDoNIN7W0GQR2LFVi=>
TE-12 M3nJOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NG\QSnRKSzVyPUSuOVY{QTRizszN NEP5ToxUSU6JUlXS
LU-139 NYLYUXZMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MY\JR|UxRTRwNkG4N|Uh|ryP M3Swe3NCVkeURWK=
HC-1 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{nJS2lEPTB;ND62PVQ6PCEQvF2= MVrTRW5IWkWU
COR-L279 MmKwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml7nTWM2OD12Lke1PFkyKM7:TR?= MnfsV2FPT1KHUh?=
SF268 NFvXRXNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUXJR|UxRTRwN{m5NVYh|ryP Mnz1V2FPT1KHUh?=
MC-CAR MlLuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1TxW2lEPTB;NT6wOlc2PyEQvF2= NXrRPVh{W0GQR2LFVi=>
TK10 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Moe5TWM2OD13LkO1OFY6KM7:TR?= MYPTRW5IWkWU
TE-1 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXLJR|UxRTVwNEmwNFQh|ryP M{jWPXNCVkeURWK=
NCI-H2126 M{TNOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX62UIQxUUN3ME21MlY1PTd2IN88US=> MVfTRW5IWkWU
Daudi MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoPoTWM2OD13Lk[5NVIh|ryP NGDyfo9USU6JUlXS
NCI-H1648 NXf6cYR1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoO4TWM2OD13LkixOFU1KM7:TR?= MXfTRW5IWkWU
OS-RC-2 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3n1TWlEPTB;NT65PFU6PyEQvF2= M3fGdHNCVkeURWK=
DJM-1 NGjC[ndIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3\GSWlEPTB;Nj6zOFY3PiEQvF2= M4PlNXNCVkeURWK=
LS-1034 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml\vTWM2OD14Lke1OlYh|ryP NXXDcGpCW0GQR2LFVi=>
NCI-H1581 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV;Md|RUUUN3ME22Mlc5PDB3IN88US=> MXzTRW5IWkWU
UACC-257 NYfqd3NtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVzJR|UxRTdwMES1NVIh|ryP M{DwSXNCVkeURWK=
KM-H2 Mn\DS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYC3fVdbUUN3ME23MlE5PDV5IN88US=> MnHWV2FPT1KHUh?=
NCI-H1436 Mlf2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXnucXZPUUN3ME23MlY6QTN{IN88US=> M{DUfnNCVkeURWK=
IA-LM NWT6boxHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHzYU49KSzVyPUeuPFU6KM7:TR?= MV;TRW5IWkWU
NCI-H526 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkHZTWM2OD16LkK1OlM4KM7:TR?= NX:xe2tpW0GQR2LFVi=>
GCIY NXPrOIZ4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnTKTWM2OD16LkO2PVY2KM7:TR?= MWrTRW5IWkWU
CP67-MEL MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoHDTWM2OD16LkWzNlYh|ryP NGjQTYpUSU6JUlXS
KALS-1 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3zzXGlEPTB;OD64N|g2OSEQvF2= MYrTRW5IWkWU
NCI-H1770 MlnDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn[xTWM2OD16LkmwNlY2KM7:TR?= NV:0U2k1W0GQR2LFVi=>
8-MG-BA MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVjkdWtyUUN3ME25MlMzQDR2IN88US=> NXXFeXptW0GQR2LFVi=>
KY821 NEf0TpVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4HrTGlEPTB;OT63O|Q5PCEQvF2= M4K3WnNCVkeURWK=
SNB75 NWjHbXN[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NH\4bINKSzVyPUGwMlA4PiEQvF2= MXfTRW5IWkWU
NCCIT M3j0Rmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV\JR|UxRTFzLkC1PFIh|ryP NG\UTJpUSU6JUlXS
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LB373-MEL-D NHq0VIdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUG0OnFXUUN3ME2xNU4{QDJ5IN88US=> NGTEVIVUSU6JUlXS
TALL-1 NWKzUHlyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUPJR|UxRTFzLkSwOVgh|ryP NH\NfHRUSU6JUlXS
NB69 NXXXXoVxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3TGfWlEPTB;MUGuO|cxPSEQvF2= NIrzeHZUSU6JUlXS
NCI-H1355 Mo[2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkTETWM2OD1zMT65OFI3KM7:TR?= MVjTRW5IWkWU
DMS-153 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlLBTWM2OD1zMj6wOFI3KM7:TR?= NHPWflVUSU6JUlXS
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NB1 NUXk[lZWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUXJR|UxRTF{LkK5JO69VQ>? MX\TRW5IWkWU
A3-KAW M13tV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3PIcmlEPTB;MUKuN|I{PiEQvF2= M2jlbXNCVkeURWK=
NCI-H1882 MlvjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXzzWWJzUUN3ME2xNk41ODZ4IN88US=> Mor3V2FPT1KHUh?=
KG-1 NGjtTW9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV7JR|UxRTF{Lk[1OFUh|ryP NUPjR4t4W0GQR2LFVi=>
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HCE-T NILCWFBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NIrLWZNKSzVyPUGzMlAxPDlizszN MnnWV2FPT1KHUh?=
NEC8 M2Dxfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHGyNJJKSzVyPUGzMlExOzhizszN NHPLU3lUSU6JUlXS
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EW-3 M2GzSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXLJR|UxRTF|Lke0NFIh|ryP NWW0ZXVmW0GQR2LFVi=>
CTB-1 MmHOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWTUSmx7UUN3ME2xOE4xOzJ7IN88US=> M4qwVHNCVkeURWK=
LS-123 NW\IRpd{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUjkW5lHUUN3ME2xOE4yPTh6IN88US=> M1GyRnNCVkeURWK=
NCI-H1417 M2DpbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGf5S3VKSzVyPUG0MlMxPTJizszN M2PEZnNCVkeURWK=
MZ7-mel MnzlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUD3WZB5UUN3ME2xOE41PDN|IN88US=> NGnwWXRUSU6JUlXS
JiyoyeP-2003 NEjuSoNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnX1TWM2OD1zNT62N|I3KM7:TR?= MkiwV2FPT1KHUh?=
ES6 MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV\JR|UxRTF4LkKzOlEh|ryP M1f6XHNCVkeURWK=
HH M2jVXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGfId2pKSzVyPUG3MlE6PjNizszN NWe1OI5HW0GQR2LFVi=>
SF539 MmLwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGrhO49KSzVyPUG3Mlk6OjJizszN Mn;vV2FPT1KHUh?=
Calu-6 NVfJdo1bT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmLuTWM2OD1zOT6yN|kh|ryP NFfIR5hUSU6JUlXS
SK-MM-2 MmX6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NV3zcIo6UUN3ME2xPU42PTVizszN MnWzV2FPT1KHUh?=
IST-MES1 Mk\NS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4T4fWlEPTB;MUmuOlY3OyEQvF2= NH\GZY9USU6JUlXS
GI-ME-N NX;zV|EzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGrncZBKSzVyPUG5MlgzOjdizszN M3u3VnNCVkeURWK=
CAL-148 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2nmVWlEPTB;MkCuPVk{PCEQvF2= MV\TRW5IWkWU
EVSA-T NGTTOYhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mni1TWM2OD1{MT6xOFk6KM7:TR?= MljFV2FPT1KHUh?=
LP-1 NYfMR3JVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXzJR|UxRTJzLkO0N|Ih|ryP Mn25V2FPT1KHUh?=
BOKU NXHhZoMxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX7MRXdSUUN3ME2yNU41PTN|IN88US=> M1v2UnNCVkeURWK=
KLE NX:5V49DT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2TqOmlEPTB;MkKuNVkxOyEQvF2= MoLYV2FPT1KHUh?=
LB831-BLC MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV;JR|UxRTJ3LkG1NlYh|ryP MlX0V2FPT1KHUh?=
NCI-H889 NUjUWIx7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVzJR|UxRTJ3LkG5N|Eh|ryP NVrxN2ZSW0GQR2LFVi=>
REH NX;oRZJbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUDMNIVVUUN3ME2yOU41PjdzIN88US=> NInlNGdUSU6JUlXS
KP-N-RT-BM-1 Moq0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIfUb41KSzVyPUK1MlQ4PTJizszN NVfPSXY2W0GQR2LFVi=>
MPP-89 MkTLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVnJR|UxRTJ3LkWzNVQh|ryP MnfrV2FPT1KHUh?=
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NCI-H748 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mo\DTWM2OD1{NT63OlI4KM7:TR?= M3Xoc3NCVkeURWK=
LB2518-MEL NIH0eW5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX\JR|UxRTJ5LkG3O|Mh|ryP NF;rfnJUSU6JUlXS
TGBC1TKB MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFj6NlFKSzVyPUK3MlU2QDVizszN NWHOWVBlW0GQR2LFVi=>
MHH-PREB-1 MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFLuVXRKSzVyPUK4MlA4OzRizszN MoXNV2FPT1KHUh?=
MZ2-MEL NIDVZ2xIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3nyR2lEPTB;MkiuOlE1OyEQvF2= NXjKbpgyW0GQR2LFVi=>
U-266 NFrkR5pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVnJR|UxRTJ6Lk[zOlYh|ryP NHL5ZmtUSU6JUlXS
SNU-C1 M1PwXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnniTWM2OD1{OD65OFMh|ryP MXLTRW5IWkWU
SW962 NX\0[nd1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHHIdpVKSzVyPUOwMlI4PDdizszN NVHnWmtJW0GQR2LFVi=>
Raji M3KxSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUHJR|UxRTNyLkW1PVIh|ryP M1P0e3NCVkeURWK=
KNS-42 NELYSlRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2H0UmlEPTB;M{CuPFk2PiEQvF2= MYLTRW5IWkWU
LB996-RCC M1P4Smdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFTlR3ZKSzVyPUOxMlE4ODJizszN NXf2WYU3W0GQR2LFVi=>
CHP-126 NWXVWZJMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{WzVmlEPTB;M{GuNVk5PCEQvF2= MWHTRW5IWkWU
RXF393 MmHkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHW0WXVKSzVyPUOyMlQ6PyEQvF2= MXLTRW5IWkWU
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A253 MnH6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYmw[2pZUUN3ME2zN{42QDV{IN88US=> NXfTZZJVW0GQR2LFVi=>
KNS-81-FD MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmfGTWM2OD1|ND61OFU3KM7:TR?= M4K5c3NCVkeURWK=
TE-441-T NHLtc4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkPjTWM2OD1|ND62N|cyKM7:TR?= Mme4V2FPT1KHUh?=
HCC2157 M2XBWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVTJR|UxRTN3LkS2NVkh|ryP MXPTRW5IWkWU
ES3 NU\RNWtUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NV;URmtmUUN3ME2zOk43PzVizszN NGXQVWNUSU6JUlXS
NCI-H1155 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnfCTWM2OD1|Nz64NVUh|ryP MnLjV2FPT1KHUh?=
SNU-C2B NHu5V41Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYroV3JFUUN3ME2zPE4yPjV2IN88US=> MYnTRW5IWkWU
JAR NWXPZo0zT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXTJR|UxRTN6LkK0OFkh|ryP MYTTRW5IWkWU
GDM-1 NEPmbGpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHqzSmlKSzVyPUO4MlkyOTZizszN MmLNV2FPT1KHUh?=
KU812 M1fCXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1L4TWlEPTB;NEGuOVA4KM7:TR?= MUjTRW5IWkWU
BC-1 Mni3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3jnTGlEPTB;NEKuOlc{OSEQvF2= MmG0V2FPT1KHUh?=
GI-1 M4Pidmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnOwTWM2OD12Mj65NVkzKM7:TR?= MVXTRW5IWkWU
NCI-H1694 NYiy[HRRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MU\JR|UxRTR2Lkm0O|Ih|ryP MVPTRW5IWkWU
DG-75 NGfjSHlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{XHbmlEPTB;NEWuNVU4PyEQvF2= MmKwV2FPT1KHUh?=
COR-L88 M2nmeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4Lqc2lEPTB;NEWuNlc4QCEQvF2= MlrOV2FPT1KHUh?=
LS-513 M2HkVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUTxUGZxUUN3ME20OU46OTV4IN88US=> NY\wSm41W0GQR2LFVi=>
HD-MY-Z MoTBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVLJR|UxRTR4LkS2NVIh|ryP NI[yd5pUSU6JUlXS
L-363 NHvQSlhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHLQ[4FKSzVyPUS2Mlg5OSEQvF2= MVjTRW5IWkWU
TE-6 NILjfIhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYHJR|UxRTR6LkS0OkDPxE1? MXXTRW5IWkWU
NCI-H345 M{mzfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlzrTWM2OD12OD60Olgh|ryP M{LqOHNCVkeURWK=
TE-5 NXO1eWxkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1jBTmlEPTB;NEmuO|EyQCEQvF2= NWrnOIFKW0GQR2LFVi=>

... 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 <1 mg/mL
Ethanol <1 mg/mL
In vivo 30% PEG400+0.5% Tween80+5% propylene glycol 30 mg/mL

* 1 mg/ml means slightly soluble or insoluble.
* 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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*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

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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