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 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{LQdWlEPTB;MD6wNFM{QCEQvF2= NFvI[4JUSU6JUlXS
RS4-11 NY\RRpJxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYfWWnNIUUN3ME2wMlAxPDB2IN88US=> NXvKcJJKW0GQR2LFVi=>
MFH-ino M{LXVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXHL[mYyUUN3ME2wMlAxQTlizszN Mn75V2FPT1KHUh?=
NTERA-S-cl-D1 Mn3LS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{nwXGlEPTB;MD6wNVQ{PCEQvF2= NIHTO3ZUSU6JUlXS
697 M2WxSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYi0cYpFUUN3ME2wMlAzPDdzIN88US=> NE\1OYdUSU6JUlXS
NALM-6 Mnz1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYTJR|UxRTBwMEK1OVIh|ryP MXPTRW5IWkWU
ES8 NUPjb|Z1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEfLTXlKSzVyPUCuNFQ3OTNizszN NYLJWJJZW0GQR2LFVi=>
HUTU-80 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX7JR|UxRTBwMEWyPVkh|ryP NEHNT4ZUSU6JUlXS
MV-4-11 MknMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXXrTY1[UUN3ME2wMlA4Pzh{IN88US=> M1;SeHNCVkeURWK=
MONO-MAC-6 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEjySohKSzVyPUCuNFc5PzlizszN NGTPPGRUSU6JUlXS
LC-2-ad Mk\nS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHL4NFZKSzVyPUCuNFg4QDlizszN NX\4e3R3W0GQR2LFVi=>
BL-41 M3\LZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn3iTWM2OD1yLkGwOFQ2KM7:TR?= M{\0PHNCVkeURWK=
A4-Fuk MnPVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{KwWmlEPTB;MD6xNVU3OyEQvF2= Mm\HV2FPT1KHUh?=
SW954 NV:5V3NNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoTUTWM2OD1yLkGyNlI6KM7:TR?= NF3vNnVUSU6JUlXS
BV-173 NHfwW4lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHHTRYpKSzVyPUCuNVI3PDFizszN Ml3lV2FPT1KHUh?=
TE-11 NFrGO3pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUnzVldzUUN3ME2wMlE1QTh{IN88US=> M3KxZXNCVkeURWK=
SK-UT-1 MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXju[mduUUN3ME2wMlE2QTZ3IN88US=> M1y2cXNCVkeURWK=
SIG-M5 M36xOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEHnNnBKSzVyPUCuNVY4ODdizszN NFrIe4ZUSU6JUlXS
OCUB-M NH[4W5NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFPiTFhKSzVyPUCuNVY6QDNizszN NEnVXZZUSU6JUlXS
K052 M4\TZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXjNem1CUUN3ME2wMlE6PDhizszN MmS4V2FPT1KHUh?=
VA-ES-BJ NV\aRpFIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWLvOWdzUUN3ME2wMlIxODh4IN88US=> NW\uW4tCW0GQR2LFVi=>
SW982 NUW4SmV5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWnJR|UxRTBwMkGzPEDPxE1? M1XmSnNCVkeURWK=
LB647-SCLC M3XhVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2n1NWlEPTB;MD6yNVUzOyEQvF2= MVjTRW5IWkWU
PSN1 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mo\RTWM2OD1yLkKyNFI3KM7:TR?= MV7TRW5IWkWU
BB30-HNC NFqxcY1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1vTRWlEPTB;MD6yNlU6OSEQvF2= Mmn1V2FPT1KHUh?=
ST486 M1rONGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnTLTWM2OD1yLkKzNFg4KM7:TR?= MoPGV2FPT1KHUh?=
MOLT-4 NVHIdmJ6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYjJR|UxRTBwMkOzN|ch|ryP MWDTRW5IWkWU
EW-16 NEnie4JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVzxdI5mUUN3ME2wMlI{PzZ6IN88US=> MUHTRW5IWkWU
KS-1 M1zVVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVvJR|UxRTBwMkO3PFUh|ryP NFPNTGZUSU6JUlXS
SR NYK0O2loT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1S0PGlEPTB;MD6yOFU3PCEQvF2= NYCzPINjW0GQR2LFVi=>
KM12 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NELCeFdKSzVyPUCuNlY{PiEQvF2= NE\nZ4pUSU6JUlXS
EM-2 NYDTWnRVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGX6bYpKSzVyPUCuNlY3PDFizszN NVrPO5k4W0GQR2LFVi=>
MEG-01 MoThS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWTJR|UxRTBwMke4OFkh|ryP MV;TRW5IWkWU
NB13 NX36dot7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoHMTWM2OD1yLkK3PVg1KM7:TR?= NYH0TW94W0GQR2LFVi=>
RKO NFz2V4VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mkn2TWM2OD1yLkOwPFE{KM7:TR?= NFPBcWtUSU6JUlXS
CESS M1jJfmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnfHTWM2OD1yLkOxN|I5KM7:TR?= NIfWbIJUSU6JUlXS
EoL-1-cell MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGPnd5hKSzVyPUCuN|M1PTlizszN M4rSV3NCVkeURWK=
DOHH-2 M{HGR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NITxNG1KSzVyPUCuN|M4QDFizszN NWLLNVVLW0GQR2LFVi=>
A388 MmXiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWHJR|UxRTBwM{SwPFYh|ryP M2f4dXNCVkeURWK=
LAMA-84 NGfaWVRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MW\JR|UxRTBwM{WxO|gh|ryP MVvTRW5IWkWU
IMR-5 MnrFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NY\SdGQ5UUN3ME2wMlM2PTRizszN Mk\rV2FPT1KHUh?=
KARPAS-422 NGLQPWRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnzETWM2OD1yLkO3NlczKM7:TR?= MUDTRW5IWkWU
MRK-nu-1 NX73blRrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYHMbYh1UUN3ME2wMlM5OTNizszN MmLqV2FPT1KHUh?=
BL-70 NF3OZ|BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFm1c2ZKSzVyPUCuN|g6PzRizszN MVfTRW5IWkWU
LXF-289 MojCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmjrTWM2OD1yLkSwOFA3KM7:TR?= NWq4[2piW0GQR2LFVi=>
RL95-2 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmTFTWM2OD1yLkSwOVY4KM7:TR?= NEn2W|ZUSU6JUlXS
QIMR-WIL MnjiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NW\h[IhXUUN3ME2wMlQzPjd4IN88US=> M{P2fHNCVkeURWK=
K-562 NXjZRmxHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4rxOmlEPTB;MD60N|Q4OiEQvF2= M4C0WHNCVkeURWK=
NCI-H510A Mki1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHXXSXlKSzVyPUCuOFM5OjNizszN M3z2SnNCVkeURWK=
NCI-H524 NYjVUHI5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYfJR|UxRTBwNUGxOFch|ryP M2nYPHNCVkeURWK=
KE-37 NYizSpBlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVH5fWNFUUN3ME2wMlUzOTB{IN88US=> M3WycXNCVkeURWK=
KP-N-YS M{LIbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlTWTWM2OD1yLkW0N|kzKM7:TR?= NV3ud2JpW0GQR2LFVi=>
LS-411N M{DrfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWDJR|UxRTBwNUe3OVIh|ryP MYnTRW5IWkWU
CTV-1 NYLubHNMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2Cx[2lEPTB;MD61PFc4OyEQvF2= MX\TRW5IWkWU
NCI-SNU-16 NWGyfVhNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{LHRmlEPTB;MD62N|U4OSEQvF2= Mnr1V2FPT1KHUh?=
HT-144 NH32N4dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYfJR|UxRTBwNkO3PVgh|ryP MnfiV2FPT1KHUh?=
NCI-H187 NHT1ZpdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGjSb2FKSzVyPUCuOlQyOyEQvF2= Mn[2V2FPT1KHUh?=
OCI-AML2 NHrnSXdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVLpXHBvUUN3ME2wMlY1PDB|IN88US=> MorDV2FPT1KHUh?=
CCRF-CEM NGX1b3VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUXJR|UxRTBwNkWzOFYh|ryP NETufYNUSU6JUlXS
ONS-76 M1LCdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVHJR|UxRTBwNk[0OVgh|ryP NGDj[FVUSU6JUlXS
IST-SL2 NUS0VmlbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWjJR|UxRTBwN{G5PFIh|ryP MXfTRW5IWkWU
NB6 NHjsV5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFPWVphKSzVyPUCuO|czPTRizszN M2PLWXNCVkeURWK=
SK-PN-DW MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH3Rb4dKSzVyPUCuO|kyPCEQvF2= NY\ifmt{W0GQR2LFVi=>
HCC1599 NIL4T41Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{fHW2lEPTB;MD64NFg4PCEQvF2= MlHnV2FPT1KHUh?=
MC116 MkLFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mlf0TWM2OD1yLki1NFEyKM7:TR?= MU\TRW5IWkWU
TE-15 NHTtTGNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFLsXmhKSzVyPUCuPFUxQThizszN M4TQZnNCVkeURWK=
HOP-62 M1nRTGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MU\JR|UxRTBwOE[zNlkh|ryP MlPZV2FPT1KHUh?=
TGBC24TKB NYX0OFFuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MW\JR|UxRTBwOE[zPFUh|ryP NH7oe2NUSU6JUlXS
HCE-4 NYiwSoJET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGDxOIFKSzVyPUCuPFgxPjNizszN NWnNdI5JW0GQR2LFVi=>
ALL-PO NWm0[W9[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGPjUJBKSzVyPUCuPFgyPzVizszN MnjwV2FPT1KHUh?=
KGN M13ISGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoG3TWM2OD1yLki5PVk2KM7:TR?= MXXTRW5IWkWU
ML-2 NEfsfFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHzy[oNKSzVyPUCuPVAzPTlizszN MWHTRW5IWkWU
ES4 M3L5cWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NULNOYN1UUN3ME2wMlkyOTJ6IN88US=> MmL4V2FPT1KHUh?=
SF126 NFzvdFZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2HqeWlEPTB;MD65OFgyQSEQvF2= NVfSXodGW0GQR2LFVi=>
SK-N-DZ NVzBNGxxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2nrZWlEPTB;MD65OlE5QSEQvF2= NUGzbIJOW0GQR2LFVi=>
HCC1187 M1fIZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1v5WGlEPTB;MT6wNFUxPSEQvF2= NELVcIxUSU6JUlXS
DU-4475 NETVOIlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVPJR|UxRTFwMEG3OVYh|ryP NXvP[mxiW0GQR2LFVi=>
NKM-1 M4rVfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXTJR|UxRTFwMEK3O|Uh|ryP M4X1SXNCVkeURWK=
HL-60 NYrOTXJHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUDVSYJ7UUN3ME2xMlA3PTd2IN88US=> NE\VRWpUSU6JUlXS
SBC-1 NY\qeHpLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MoezTWM2OD1zLkGyOVQzKM7:TR?= MWPTRW5IWkWU
TE-10 NUCxPY93T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEnFSGVKSzVyPUGuNVI6PDZizszN NGrzcXlUSU6JUlXS
ETK-1 M3PPW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3mx[2lEPTB;MT6xN|YyOyEQvF2= NYm0Zo5sW0GQR2LFVi=>
HAL-01 Ml;aS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mli3TWM2OD1zLkG2O|A6KM7:TR?= MVfTRW5IWkWU
BB65-RCC NWT1VI97T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHjDPJNKSzVyPUGuNVgxODVizszN M3P6THNCVkeURWK=
EW-1 NGTWdlFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlHTTWM2OD1zLkG4OVYzKM7:TR?= MUHTRW5IWkWU
SK-NEP-1 Moe2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2nGdmlEPTB;MT6yNVEyOSEQvF2= MnLyV2FPT1KHUh?=
SK-LMS-1 MmDzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1XOR2lEPTB;MT6yNlIyOiEQvF2= MkOzV2FPT1KHUh?=
DEL M{Hxd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX\6RoZqUUN3ME2xMlI2PjR|IN88US=> MkTDV2FPT1KHUh?=
GT3TKB M13LUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{\HVWlEPTB;MT6yPFA2PyEQvF2= MUDTRW5IWkWU
MOLT-16 M2HZeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml\OTWM2OD1zLkO1OFA2KM7:TR?= NHP2SVVUSU6JUlXS
CMK NInpdY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHfpeGFKSzVyPUGuOFIyOTdizszN M{PCUHNCVkeURWK=
NB5 M{LmU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXi0VGNFUUN3ME2xMlY1OjJ7IN88US=> NFr0VXpUSU6JUlXS
NCI-H1963 NIfEdIhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{niXGlEPTB;MT63NFU5OyEQvF2= Mn;SV2FPT1KHUh?=
KURAMOCHI MmHnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYrJR|UxRTFwN{i5NVEh|ryP M2L0NHNCVkeURWK=
TE-8 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXPJR|UxRTFwOECzOlgh|ryP NEDQbJhUSU6JUlXS
NCI-H1304 M2HqTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mlz6TWM2OD1zLkizNFc{KM7:TR?= MnPLV2FPT1KHUh?=
A101D NYXUSJA3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUTJR|UxRTFwOEezPVUh|ryP NG\ybGNUSU6JUlXS
SCLC-21H NH7E[FlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUjJR|UxRTFwOUewOVch|ryP NW[1b4VTW0GQR2LFVi=>
GB-1 NVPWPJVCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVLJR|UxRTJwMEG2OFch|ryP NEPFd4VUSU6JUlXS
KARPAS-45 NWTNe2I1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVTJR|UxRTJwMEK2OVQh|ryP M1fp[nNCVkeURWK=
ATN-1 NHznS|ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1K4fGlEPTB;Mj6wNlg2QCEQvF2= MULTRW5IWkWU
NCI-H720 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF\FTlVKSzVyPUKuNFYzPDRizszN M3f2UHNCVkeURWK=
RPMI-6666 MmjQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnrTTWM2OD1{LkG2NlA4KM7:TR?= MVrTRW5IWkWU
NB17 NVfFcplST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NG[3b4RKSzVyPUKuNlkzPyEQvF2= M3fqbnNCVkeURWK=
IST-SL1 MofDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MULJR|UxRTJwMkm3OlUh|ryP MW\TRW5IWkWU
SH-4 NXXNdWljT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGLIc|VKSzVyPUKuN|I1PjlizszN NXuzfGlbW0GQR2LFVi=>
K5 NX;FdJhnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV7JR|UxRTJwNECzNVkh|ryP NGfjTotUSU6JUlXS
OVCAR-4 NF;ncFdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2nvfGlEPTB;Mj60OlE{KM7:TR?= MkXHV2FPT1KHUh?=
ACN NFjHO3dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXHCV3RXUUN3ME2yMlUxOjF|IN88US=> NYnhbIpRW0GQR2LFVi=>
TGW M3v4[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NX\kUXlxUUN3ME2yMlY2QDN{IN88US=> MmnCV2FPT1KHUh?=
NCI-H2107 NYnWbXNWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4W5cmlEPTB;Mj64N|cyOSEQvF2= NFfDVZNUSU6JUlXS
NCI-H82 M4fTR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWS2PXdjUUN3ME2yMlg{QDN6IN88US=> NHLJXYJUSU6JUlXS
SK-N-FI M4XqUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mnr2TWM2OD1{Lki2PFY5KM7:TR?= NUXoXoRHW0GQR2LFVi=>
LB1047-RCC NYP0ZWplT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYDa[Xl4UUN3ME2yMlg5OTJ4IN88US=> M{DIU3NCVkeURWK=
LU-134-A NFX4[4dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXfJR|UxRTJwOEmyOkDPxE1? MYPTRW5IWkWU
NCI-H209 MnvpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NY\VTGFCUUN3ME2yMlkyOjV|IN88US=> MWLTRW5IWkWU
NOMO-1 NXHvd3RnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWHJR|UxRTNwMEKyO|Qh|ryP MXXTRW5IWkWU
RH-1 NXnEPHZCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXi5SlF5UUN3ME2zMlE4OjlzIN88US=> MUTTRW5IWkWU
LOUCY Mm\xS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3v6XmlEPTB;Mz6xPFY6OyEQvF2= NXPGemVzW0GQR2LFVi=>
TE-9 Mki0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4DZVWlEPTB;Mz6yOlc{PiEQvF2= MUXTRW5IWkWU
PF-382 NFm0WWdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVuyOpc1UUN3ME2zMlM2Pzd6IN88US=> MUTTRW5IWkWU
RPMI-8402 NH;s[G5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWnJR|UxRTNwNUi2NFMh|ryP NF7CW3RUSU6JUlXS
HEL NX3WW2FJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVjhZZhTUUN3ME2zMlY{OiEQvF2= MYfTRW5IWkWU
NOS-1 M17PZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3nVUGlEPTB;Mz64OFc2PCEQvF2= MmDPV2FPT1KHUh?=
ES1 NIXZUmtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1GzXGlEPTB;Mz65NlI6OyEQvF2= NUPr[ZJwW0GQR2LFVi=>
NCI-H2171 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEX2RlJKSzVyPUOuPVI1OjNizszN NGHwe4FUSU6JUlXS
NCI-H747 NEfDO5NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4HrWGlEPTB;Mz65OFIzOSEQvF2= MV7TRW5IWkWU
MHH-NB-11 MkDpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmTVTWM2OD1|Lkm1N|EzKM7:TR?= NHLpdY1USU6JUlXS
MZ1-PC MmLYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXvNdINtUUN3ME2zMlk6OjRizszN MUTTRW5IWkWU
MMAC-SF NIDKcXNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVvPUlk{UUN3ME20MlAzPDZ5IN88US=> M1HzfXNCVkeURWK=
NMC-G1 NYnTWpJsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVXJR|UxRTRwMkK3NlMh|ryP MYHTRW5IWkWU
SW872 MmOxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mki3TWM2OD12LkO0N|Qh|ryP MYfTRW5IWkWU
TE-12 NUi5WZVRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M33hbmlEPTB;ND61OlM6PCEQvF2= MWrTRW5IWkWU
LU-139 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2jSc2lEPTB;ND62NVg{PSEQvF2= NGT5PWlUSU6JUlXS
HC-1 NEPNZ5hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{m3d2lEPTB;ND62PVQ6PCEQvF2= MmK4V2FPT1KHUh?=
COR-L279 MkTOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGXSeI1KSzVyPUSuO|U5QTFizszN MVjTRW5IWkWU
SF268 M1S4[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEfzb3dKSzVyPUSuO|k6OTZizszN NYTDOGNWW0GQR2LFVi=>
MC-CAR NHvEelVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGHVSVFKSzVyPUWuNFY4PTdizszN NWfLVpNMW0GQR2LFVi=>
TK10 NGfhXnhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVv2[nVYUUN3ME21MlM2PDZ7IN88US=> NITuVGpUSU6JUlXS
TE-1 NGixS21Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3npemlEPTB;NT60PVAxPCEQvF2= NEW4dYdUSU6JUlXS
NCI-H2126 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnraTWM2OD13Lk[0OVc1KM7:TR?= NGnrT4NUSU6JUlXS
Daudi M{fXZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYHOcotwUUN3ME21MlY6OTJizszN NUjBUFM2W0GQR2LFVi=>
NCI-H1648 MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEO5SFlKSzVyPUWuPFE1PTRizszN NXPsNHRuW0GQR2LFVi=>
OS-RC-2 MmPJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWjJR|UxRTVwOUi1PVch|ryP M2Wxd3NCVkeURWK=
DJM-1 MlrYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGT3WJJKSzVyPU[uN|Q3PjZizszN NGH1WFlUSU6JUlXS
LS-1034 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmPBTWM2OD14Lke1OlYh|ryP Mo\nV2FPT1KHUh?=
NCI-H1581 MnezS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGHqTnJKSzVyPU[uO|g1ODVizszN MmPXV2FPT1KHUh?=
UACC-257 NXzrS3BVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NI\QWZNKSzVyPUeuNFQ2OTJizszN M4ixVnNCVkeURWK=
KM-H2 Mn;HS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWW1UZpQUUN3ME23MlE5PDV5IN88US=> NGSzelFUSU6JUlXS
NCI-H1436 M{nT[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{e4PGlEPTB;Nz62PVk{OiEQvF2= M{iyXHNCVkeURWK=
IA-LM NFjpVVlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXzo[3FCUUN3ME23Mlg2QSEQvF2= NH\BOWFUSU6JUlXS
NCI-H526 M3zHUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYD0doV5UUN3ME24MlI2PjN5IN88US=> MmLYV2FPT1KHUh?=
GCIY MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkL6TWM2OD16LkO2PVY2KM7:TR?= MWPTRW5IWkWU
CP67-MEL NH3kNXpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnLtTWM2OD16LkWzNlYh|ryP NUXaXmZiW0GQR2LFVi=>
KALS-1 M2rnNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFLLWmdKSzVyPUiuPFM5PTFizszN MV\TRW5IWkWU
NCI-H1770 M1;Se2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXjSeI8yUUN3ME24MlkxOjZ3IN88US=> NYXJUI5UW0GQR2LFVi=>
8-MG-BA NH3MN4ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHi5N5NKSzVyPUmuN|I5PDRizszN NX7FZ3o4W0GQR2LFVi=>
KY821 M1m2[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVjFfG82UUN3ME25Mlc4PDh2IN88US=> MWfTRW5IWkWU
SNB75 NVXzdXZnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1zxcGlEPTB;MUCuNFc3KM7:TR?= M1yyS3NCVkeURWK=
NCCIT MkG3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2nmZ2lEPTB;MUGuNFU5OiEQvF2= MYjTRW5IWkWU
SJSA-1 NFq2XFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV[yUIhFUUN3ME2xNU4zQDlzIN88US=> M2DDcnNCVkeURWK=
LB373-MEL-D NUPkcIxuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3Wyc2lEPTB;MUGuN|gzPyEQvF2= MVrTRW5IWkWU
TALL-1 MmjZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NULlb3VXUUN3ME2xNU41ODV6IN88US=> M4nlcHNCVkeURWK=
NB69 Mk\6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3zCe2lEPTB;MUGuO|cxPSEQvF2= NIDiOnZUSU6JUlXS
NCI-H1355 NV25[5NXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEPmTVBKSzVyPUGxMlk1OjZizszN MofuV2FPT1KHUh?=
DMS-153 NEn3dFZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXHJR|UxRTF{LkC0NlYh|ryP MVnTRW5IWkWU
OPM-2 NIfH[IJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVLvZY9wUUN3ME2xNk4yPTl4IN88US=> MnrJV2FPT1KHUh?=
NB1 M3jvSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2L5b2lEPTB;MUKuNlkh|ryP NV;2cHNuW0GQR2LFVi=>
A3-KAW M3fkOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWXN[VdyUUN3ME2xNk4{OjN4IN88US=> NHmwdmhUSU6JUlXS
NCI-H1882 MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVv0bolYUUN3ME2xNk41ODZ4IN88US=> MX7TRW5IWkWU
KG-1 NFz2TZdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlfSTWM2OD1zMj62OVQ2KM7:TR?= NFvW[3dUSU6JUlXS
LC4-1 NXTkfYJtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml\OTWM2OD1zMj63O|A3KM7:TR?= MW\TRW5IWkWU
HCE-T NEeweJFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUTJR|UxRTF|LkCwOFkh|ryP M4HPR3NCVkeURWK=
NEC8 M13Ucmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFHUNllKSzVyPUGzMlExOzhizszN MXLTRW5IWkWU
IST-MEL1 MknFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFH6TIlKSzVyPUGzMlU4QDhizszN NH3zbHZUSU6JUlXS
EW-3 M2Dp[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUDqc5c6UUN3ME2xN{44PDB{IN88US=> NVyxRnFHW0GQR2LFVi=>
CTB-1 MnK3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml7GTWM2OD1zND6wN|I6KM7:TR?= MljkV2FPT1KHUh?=
LS-123 NHPIdo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVLTPI41UUN3ME2xOE4yPTh6IN88US=> MonhV2FPT1KHUh?=
NCI-H1417 MmHKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2nmW2lEPTB;MUSuN|A2OiEQvF2= NI\KUppUSU6JUlXS
MZ7-mel NH[zbmNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MW\JR|UxRTF2LkS0N|Mh|ryP M4jiZnNCVkeURWK=
JiyoyeP-2003 NEDuUVhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGPWUZpKSzVyPUG1MlY{OjZizszN MoHmV2FPT1KHUh?=
ES6 MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWHJR|UxRTF4LkKzOlEh|ryP NYnDbWxGW0GQR2LFVi=>
HH MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3rVRmlEPTB;MUeuNVk3OyEQvF2= NVrVZWY6W0GQR2LFVi=>
SF539 NVq4NoJCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWrJR|UxRTF5Lkm5NlIh|ryP NHXRVGNUSU6JUlXS
Calu-6 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml7ITWM2OD1zOT6yN|kh|ryP NXTPSZoxW0GQR2LFVi=>
SK-MM-2 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3S2PGlEPTB;MUmuOVU2KM7:TR?= MV3TRW5IWkWU
IST-MES1 NYDscWV3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVz6R5hVUUN3ME2xPU43PjZ|IN88US=> MnPRV2FPT1KHUh?=
GI-ME-N MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX3tTmNZUUN3ME2xPU45OjJ5IN88US=> M{\sOnNCVkeURWK=
CAL-148 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGXHUodKSzVyPUKwMlk6OzRizszN M1XOSXNCVkeURWK=
EVSA-T M4DCTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{P1[GlEPTB;MkGuNVQ6QSEQvF2= M1PnVnNCVkeURWK=
LP-1 M4ixPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXHOVmhFUUN3ME2yNU4{PDN{IN88US=> MY\TRW5IWkWU
BOKU NHzjSIZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGfpeHFKSzVyPUKxMlQ2OzNizszN NUnPWpRSW0GQR2LFVi=>
KLE MoXGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4PBNmlEPTB;MkKuNVkxOyEQvF2= M{e3TXNCVkeURWK=
LB831-BLC MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYe4ZYdZUUN3ME2yOU4yPTJ4IN88US=> MmDsV2FPT1KHUh?=
NCI-H889 NXj5S|RVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MV\JR|UxRTJ3LkG5N|Eh|ryP MmDZV2FPT1KHUh?=
REH MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2jh[GlEPTB;MkWuOFY4OSEQvF2= MV\TRW5IWkWU
KP-N-RT-BM-1 MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX\JR|UxRTJ3LkS3OVIh|ryP M4OwWnNCVkeURWK=
MPP-89 NI\zXGFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFLuOmhKSzVyPUK1MlU{OTRizszN NXruc2pnW0GQR2LFVi=>
no-11 NYLwNItjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2H4ZWlEPTB;MkWuO|Q4KM7:TR?= NHPN[2xUSU6JUlXS
NCI-H748 Mm\zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{TGWGlEPTB;MkWuO|YzPyEQvF2= NETVbpRUSU6JUlXS
LB2518-MEL MmjMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{PvfWlEPTB;MkeuNVc4OyEQvF2= NFOzW5FUSU6JUlXS
TGBC1TKB NWr6WnRLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkXlTWM2OD1{Nz61OVg2KM7:TR?= NX:1S3RMW0GQR2LFVi=>
MHH-PREB-1 NGfjc3lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHzDUpBKSzVyPUK4MlA4OzRizszN NXXYOYxJW0GQR2LFVi=>
MZ2-MEL NYmwSo8yT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYTaU3hrUUN3ME2yPE43OTR|IN88US=> MWLTRW5IWkWU
U-266 NGKxXYJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2X1SWlEPTB;MkiuOlM3PiEQvF2= MVjTRW5IWkWU
SNU-C1 NHmwTnpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoDvTWM2OD1{OD65OFMh|ryP MV\TRW5IWkWU
SW962 NVLZfWRST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX3l[HFPUUN3ME2zNE4zPzR5IN88US=> MYXTRW5IWkWU
Raji NWfyNZNUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NUXMTo5NUUN3ME2zNE42PTl{IN88US=> M3\ROnNCVkeURWK=
KNS-42 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NY\kTWkzUUN3ME2zNE45QTV4IN88US=> MYDTRW5IWkWU
LB996-RCC NXPXXXBST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVzkNWx{UUN3ME2zNU4yPzB{IN88US=> MljSV2FPT1KHUh?=
CHP-126 Mor1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3XwSWlEPTB;M{GuNVk5PCEQvF2= NXrENJl5W0GQR2LFVi=>
RXF393 MlHYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MljNTWM2OD1|Mj60PVch|ryP NEiwdVVUSU6JUlXS
COLO-684 NFHNcXpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4flbWlEPTB;M{KuOlQ{QCEQvF2= NXXjTG9GW0GQR2LFVi=>
A704 NXzkboxyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1vHe2lEPTB;M{OuOVU{QCEQvF2= NHXGVHRUSU6JUlXS
A253 NGfvN3BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MY\JR|UxRTN|LkW4OVIh|ryP Mm\YV2FPT1KHUh?=
KNS-81-FD MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXPJR|UxRTN2LkW0OVYh|ryP MVzTRW5IWkWU
TE-441-T MkKzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml;GTWM2OD1|ND62N|cyKM7:TR?= MUfTRW5IWkWU
HCC2157 M4q5cmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mo\pTWM2OD1|NT60OlE6KM7:TR?= NVmyT2NCW0GQR2LFVi=>
ES3 MmTQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NUHzd|REUUN3ME2zOk43PzVizszN Ml[zV2FPT1KHUh?=
NCI-H1155 NVnxbpFTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUDJR|UxRTN5LkixOUDPxE1? NVvOTlVbW0GQR2LFVi=>
SNU-C2B MlzXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXrJR|UxRTN6LkG2OVQh|ryP NITiXmRUSU6JUlXS
JAR MoizS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn\HTWM2OD1|OD6yOFQ6KM7:TR?= MYXTRW5IWkWU
GDM-1 Mlv4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF7sZ2RKSzVyPUO4MlkyOTZizszN NEfF[lhUSU6JUlXS
KU812 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1r5[WlEPTB;NEGuOVA4KM7:TR?= M4fBXHNCVkeURWK=
BC-1 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NX3nPJhvUUN3ME20Nk43PzNzIN88US=> NHuyeXBUSU6JUlXS
GI-1 MorKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3LYOmlEPTB;NEKuPVE6OiEQvF2= NYjNdldXW0GQR2LFVi=>
NCI-H1694 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnHtTWM2OD12ND65OFczKM7:TR?= MXPTRW5IWkWU
DG-75 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mk\UTWM2OD12NT6xOVc4KM7:TR?= MkG4V2FPT1KHUh?=
COR-L88 Mo\YS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1LxXWlEPTB;NEWuNlc4QCEQvF2= MUPTRW5IWkWU
LS-513 NG\wTnVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYPJR|UxRTR3LkmxOVYh|ryP NVXIcHVZW0GQR2LFVi=>
HD-MY-Z NXrwNHFRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHjKdphKSzVyPUS2MlQ3OTJizszN MV\TRW5IWkWU
L-363 M{fFcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MlrzTWM2OD12Nj64PFEh|ryP NWnlXlJoW0GQR2LFVi=>
TE-6 M4DtdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmXWTWM2OD12OD60OFYh|ryP NHra[XFUSU6JUlXS
NCI-H345 Ml7KS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGDOU4RKSzVyPUS4MlQ3QCEQvF2= MWTTRW5IWkWU
TE-5 M3vue2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIXq[WFKSzVyPUS5MlcyOThizszN MWrTRW5IWkWU

... Click to View More Cell Line Experimental Data

In vivo VX-680 gives rise to a marked decrease in tumor size in a human AML (HL-60) xenograft model. In mude mice treateed with VX-680 at 75 mg/kg, twice a day intraperitoneally (b.i.d. i.p.) for 13 days, mean tumor volumes are reduced by 98%. Tumor growth decrease is dose dependent and significant at a dose of 12.5 mg/kg b.i.d. VX-680 is well tolerated, with a small decrease in body weight observed only at the highest dose. VX-680 also triggers tumor regresson in pancreatic and colon xenograft models. VX-680 also displays potent antitumor activity when infused i.v. in mude rats bearing established HCT116 tumors. A higher dose of VX-680 (2 mg/kg/h) improves efficacy with a 56% decrease in mean tumor volume. [1]

Protocol

Kinase Assay:

[3]

+ Expand

Kinase inhibition assays:

The consumption of ATP is coupled via the pyruvate kinase/lactic dehydrogenase enzyme pair to the oxidation of NADH, which can be monitored through the decrease in absorption at 340 nm. Reactions contains 100 mM Tris (pH 8), 10 mM MgCl2, 2.2 mM ATP, 1 mM phosphoenolpyruvate, 0.6 mg/mL NADH, 75 units/mL pyruvate kinase, 105 units/mL lactate dehydrogenase, and 0.5 mM substrate peptide (sequence: EAIYAAPFAKKK). Reactions (75 μL) are started by adding sufficient kinase to bring the reactions to 30 nM kinase concentration and the decrease in absorbance is monitored over 30 minutes at 30°C in a microtiter plate spectrophotometer. Inhibitory constants are obtained through addition of 3.75 μL VX-680 in 100% DMSO or DMSO alone. Ki values are calculated as follows, K i = IC50 / (1 + [S]/Kd), where [S] = [ATP] = 2.2 mM, and Kd (of ATP to Abl) = 70 μM. These values are calculated assuming a Kd (ATP) of 70 μM for wild type and H396P Abl kinase domain.
Cell Research:

[2]

+ Expand
  • Cell lines: CAL-62 cells
  • Concentrations: 5-500 nM
  • Incubation Time: 4 days
  • Method:

    The CAL-62 cells are cultured in the absence (dimethyl sulfoxide, DMSO) or the presence of 500  nM VX-680 for different periods of time (1-5 days). The dose-dependent effects of VX-680 on cell proliferation are evaluated by treating the different ATC cells for 4 days with different concentrations of the Aurora inhibitor (5–500  nM). The cells are pulse labeled with 30  mM BrdU for 2  hours before the end of the incubation time. The BrdU incorporation is analyzed by means of a colorimetric immunoassay using the cell proliferation ELISA kit. The results from VX-680-treated cells are compared with those observed in control cells and expressed as a fold of variation versus control.


    (Only for Reference)
Animal Research:

[1]

+ Expand
  • Animal Models: Female athymic NCr-nu mice bearing HL-60 leukemia cells
  • Formulation: 50% PEG300 in 50 mM phosphate buffer
  • Dosages: 50 mg/kg, 75 mg/kg
  • Administration: Administered via i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 93 mg/mL (200.17 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents individually and in order:
5% DMSO+30% PEG 300+2% Tween 80+ddH2O
15mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 464.59
Formula

C23H28N8OS

CAS No. 639089-54-6
Storage powder
Synonyms N/A

Bio Calculators

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Molarity Calculator

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

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*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

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

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

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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