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
USD 147 In stock
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 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYXJR|UxRTBwMECzN|gh|ryP M3rj[XNCVkeURWK=
RS4-11 Mn3CS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlLxTWM2OD1yLkCwOFA1KM7:TR?= M3q5eHNCVkeURWK=
MFH-ino M3LlUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVvYVYpNUUN3ME2wMlAxQTlizszN MWfTRW5IWkWU
NTERA-S-cl-D1 NHvzPGlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEn1bIhKSzVyPUCuNFE1OzRizszN NYfrbZBoW0GQR2LFVi=>
697 M3PVeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnTHTWM2OD1yLkCyOFcyKM7:TR?= M2rxOXNCVkeURWK=
NALM-6 NIm3dnBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{nIZWlEPTB;MD6wNlU2OiEQvF2= M1P6NHNCVkeURWK=
ES8 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHq5dZlKSzVyPUCuNFQ3OTNizszN NYL3dW9UW0GQR2LFVi=>
HUTU-80 M3\IXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M333dmlEPTB;MD6wOVI6QSEQvF2= MmDjV2FPT1KHUh?=
MV-4-11 M1PEbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1e3OWlEPTB;MD6wO|c5OiEQvF2= M1n1VnNCVkeURWK=
MONO-MAC-6 M1\IU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYjJR|UxRTBwMEe4O|kh|ryP NEfFUHFUSU6JUlXS
LC-2-ad MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4fsfmlEPTB;MD6wPFc5QSEQvF2= NGnPfmdUSU6JUlXS
BL-41 NH\tcJpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEHteIVKSzVyPUCuNVA1PDVizszN MnXQV2FPT1KHUh?=
A4-Fuk MoHvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn6xTWM2OD1yLkGxOVY{KM7:TR?= M2rnOHNCVkeURWK=
SW954 NGT6OHpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{TQUGlEPTB;MD6xNlIzQSEQvF2= NYjGRo8{W0GQR2LFVi=>
BV-173 MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUDJR|UxRTBwMUK2OFEh|ryP M4fBV3NCVkeURWK=
TE-11 NFW2TJVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVn2dJNCUUN3ME2wMlE1QTh{IN88US=> NYi1c4dZW0GQR2LFVi=>
SK-UT-1 MlXCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEjM[|FKSzVyPUCuNVU6PjVizszN MnnWV2FPT1KHUh?=
SIG-M5 MonXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIDOO49KSzVyPUCuNVY4ODdizszN NFLjRXpUSU6JUlXS
OCUB-M MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWjJR|UxRTBwMU[5PFMh|ryP NXnaZ2VyW0GQR2LFVi=>
K052 NIHSNItIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkHITWM2OD1yLkG5OFgh|ryP M1PwTXNCVkeURWK=
VA-ES-BJ M{H4[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV7JR|UxRTBwMkCwPFYh|ryP NH2yOnlUSU6JUlXS
SW982 MkezS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnrqTWM2OD1yLkKxN|gh|ryP MmjTV2FPT1KHUh?=
LB647-SCLC M12wXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYrJR|UxRTBwMkG1NlMh|ryP MoTkV2FPT1KHUh?=
PSN1 NULkPHhsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYq2[nF[UUN3ME2wMlIzODJ4IN88US=> NVLrWHRqW0GQR2LFVi=>
BB30-HNC NFjoR2lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mo[3TWM2OD1yLkKyOVkyKM7:TR?= M4DCV3NCVkeURWK=
ST486 NUfvdJVmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWnJR|UxRTBwMkOwPFch|ryP MX;TRW5IWkWU
MOLT-4 MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWHJR|UxRTBwMkOzN|ch|ryP MWTTRW5IWkWU
EW-16 M1\hUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NV[yV5F[UUN3ME2wMlI{PzZ6IN88US=> NVrTWFczW0GQR2LFVi=>
KS-1 MofBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWjJR|UxRTBwMkO3PFUh|ryP M4fCU3NCVkeURWK=
SR MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mn;UTWM2OD1yLkK0OVY1KM7:TR?= MmLSV2FPT1KHUh?=
KM12 M{LpSmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV3JR|UxRTBwMk[zOkDPxE1? MkPpV2FPT1KHUh?=
EM-2 Mke0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkXOTWM2OD1yLkK2OlQyKM7:TR?= MnK5V2FPT1KHUh?=
MEG-01 MmDvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml7HTWM2OD1yLkK3PFQ6KM7:TR?= MWPTRW5IWkWU
NB13 NH\yT5lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHnT[29KSzVyPUCuNlc6QDRizszN NYHSeG9kW0GQR2LFVi=>
RKO M4LI[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVzyb5VoUUN3ME2wMlMxQDF|IN88US=> MVLTRW5IWkWU
CESS M4HJNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYDJR|UxRTBwM{GzNlgh|ryP MY\TRW5IWkWU
EoL-1-cell Ml7XS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX7JR|UxRTBwM{O0OVkh|ryP NVXWdZdpW0GQR2LFVi=>
DOHH-2 M4f0VGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoHPTWM2OD1yLkOzO|gyKM7:TR?= M3\4XHNCVkeURWK=
A388 NVPXOVZzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1:xNWlEPTB;MD6zOFA5PiEQvF2= NHLQR21USU6JUlXS
LAMA-84 NYXwfopNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MkTCTWM2OD1yLkO1NVc5KM7:TR?= Ml3SV2FPT1KHUh?=
IMR-5 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIGzNm9KSzVyPUCuN|U2PCEQvF2= NEHVUG1USU6JUlXS
KARPAS-422 MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEP2ZWpKSzVyPUCuN|czPzJizszN MlPMV2FPT1KHUh?=
MRK-nu-1 MoXHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEPkWJRKSzVyPUCuN|gyOyEQvF2= M3jDSnNCVkeURWK=
BL-70 Mor3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn;UTWM2OD1yLkO4PVc1KM7:TR?= M4PBfHNCVkeURWK=
LXF-289 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mof5TWM2OD1yLkSwOFA3KM7:TR?= MXfTRW5IWkWU
RL95-2 NWr2fm9GT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWPacVBwUUN3ME2wMlQxPTZ5IN88US=> NIny[I9USU6JUlXS
QIMR-WIL MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFjmfGRKSzVyPUCuOFI3PzZizszN MXLTRW5IWkWU
K-562 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3PZcGlEPTB;MD60N|Q4OiEQvF2= MlXVV2FPT1KHUh?=
NCI-H510A MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Mm[zTWM2OD1yLkSzPFI{KM7:TR?= M{HxRXNCVkeURWK=
NCI-H524 M1PSU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoLzTWM2OD1yLkWxNVQ4KM7:TR?= M2XoU3NCVkeURWK=
KE-37 MlfMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mo\KTWM2OD1yLkWyNVAzKM7:TR?= NWLLSmYzW0GQR2LFVi=>
KP-N-YS M1XMTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHjyXohKSzVyPUCuOVQ{QTJizszN MUPTRW5IWkWU
LS-411N NGPXV4VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlzjTWM2OD1yLkW3O|UzKM7:TR?= MUPTRW5IWkWU
CTV-1 MoXOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{WzRmlEPTB;MD61PFc4OyEQvF2= Mn34V2FPT1KHUh?=
NCI-SNU-16 NWO2UlUyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{XQXWlEPTB;MD62N|U4OSEQvF2= Ml;nV2FPT1KHUh?=
HT-144 M2rsO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUL1XJQ1UUN3ME2wMlY{Pzl6IN88US=> NVHReIdCW0GQR2LFVi=>
NCI-H187 M4rZXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml7sTWM2OD1yLk[0NVMh|ryP NEH1OHhUSU6JUlXS
OCI-AML2 MlfQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4HYSGlEPTB;MD62OFQxOyEQvF2= MkXUV2FPT1KHUh?=
CCRF-CEM NF;2colIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2[4SGlEPTB;MD62OVM1PiEQvF2= NHnp[oVUSU6JUlXS
ONS-76 Mly4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVTJR|UxRTBwNk[0OVgh|ryP MoLQV2FPT1KHUh?=
IST-SL2 NWjBfXllT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NW\T[JFVUUN3ME2wMlcyQTh{IN88US=> MmPEV2FPT1KHUh?=
NB6 NWXhdm1XT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M17ydGlEPTB;MD63O|I2PCEQvF2= MYjTRW5IWkWU
SK-PN-DW M2DvVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3y3[2lEPTB;MD63PVE1KM7:TR?= NX3v[YZoW0GQR2LFVi=>
HCC1599 Mn3FS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2L2R2lEPTB;MD64NFg4PCEQvF2= NXnTN3dWW0GQR2LFVi=>
MC116 MnHDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEDOcHpKSzVyPUCuPFUxOTFizszN NWXrXY5YW0GQR2LFVi=>
TE-15 M2TGXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2PxV2lEPTB;MD64OVA6QCEQvF2= MlHiV2FPT1KHUh?=
HOP-62 Mki2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWPkfY9jUUN3ME2wMlg3OzJ7IN88US=> MX;TRW5IWkWU
TGBC24TKB MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXLJR|UxRTBwOE[zPFUh|ryP NXrPRWUzW0GQR2LFVi=>
HCE-4 NHjmRY9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX;JR|UxRTBwOEiwOlMh|ryP MnTBV2FPT1KHUh?=
ALL-PO M{PFPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mof1TWM2OD1yLki4NVc2KM7:TR?= MXjTRW5IWkWU
KGN NYHCdGdtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnPmTWM2OD1yLki5PVk2KM7:TR?= MkPoV2FPT1KHUh?=
ML-2 NXLhUZFmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1P5bWlEPTB;MD65NFI2QSEQvF2= MVzTRW5IWkWU
ES4 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NIDab5BKSzVyPUCuPVEyOjhizszN MYrTRW5IWkWU
SF126 NUnWPI17T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWDwfZdpUUN3ME2wMlk1QDF7IN88US=> NF3xeJNUSU6JUlXS
SK-N-DZ NGTCRVdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3K2dGlEPTB;MD65OlE5QSEQvF2= NF2wVVJUSU6JUlXS
HCC1187 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVzvV2d3UUN3ME2xMlAxPTB3IN88US=> NYTVU|NkW0GQR2LFVi=>
DU-4475 NX:2ZohkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1HZUWlEPTB;MT6wNVc2PiEQvF2= MlHWV2FPT1KHUh?=
NKM-1 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUTJR|UxRTFwMEK3O|Uh|ryP NUDMS|hzW0GQR2LFVi=>
HL-60 M33ufWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M17QSmlEPTB;MT6wOlU4PCEQvF2= NIWyb|JUSU6JUlXS
SBC-1 NF3a[2RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFTHNHpKSzVyPUGuNVI2PDJizszN Mn[2V2FPT1KHUh?=
TE-10 Mo\aS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFrJSIlKSzVyPUGuNVI6PDZizszN MVXTRW5IWkWU
ETK-1 NGLoe4dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFzBSZRKSzVyPUGuNVM3OTNizszN M2XtdHNCVkeURWK=
HAL-01 MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NI[3RotKSzVyPUGuNVY4ODlizszN MVvTRW5IWkWU
BB65-RCC M3\oWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVy2Nnk1UUN3ME2xMlE5ODB3IN88US=> M4XQW3NCVkeURWK=
EW-1 MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MlXRTWM2OD1zLkG4OVYzKM7:TR?= M4LsO3NCVkeURWK=
SK-NEP-1 M1z1Rmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmS2TWM2OD1zLkKxNVEyKM7:TR?= NWPkd4lWW0GQR2LFVi=>
SK-LMS-1 MliwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGXxXZNKSzVyPUGuNlIzOTJizszN M3jwbXNCVkeURWK=
DEL MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYLsN3lYUUN3ME2xMlI2PjR|IN88US=> NXn5[mdiW0GQR2LFVi=>
GT3TKB NGLBNYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYrJR|UxRTFwMkiwOVch|ryP NYPJW4JvW0GQR2LFVi=>
MOLT-16 M3H1cmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NULwc3UyUUN3ME2xMlM2PDB3IN88US=> NVfQWIJpW0GQR2LFVi=>
CMK NEHYdlhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYDJR|UxRTFwNEKxNVch|ryP NWPSe257W0GQR2LFVi=>
NB5 MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MoLITWM2OD1zLk[0NlI6KM7:TR?= MWXTRW5IWkWU
NCI-H1963 NUnNeHNHT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXuxWVltUUN3ME2xMlcxPTh|IN88US=> NI\zbohUSU6JUlXS
KURAMOCHI NHixRWNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVzJR|UxRTFwN{i5NVEh|ryP NXvKOVVlW0GQR2LFVi=>
TE-8 M3vVZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mlj5TWM2OD1zLkiwN|Y5KM7:TR?= NX;xSlZIW0GQR2LFVi=>
NCI-H1304 Ml;yS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkXPTWM2OD1zLkizNFc{KM7:TR?= M2XH[XNCVkeURWK=
A101D MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYDJR|UxRTFwOEezPVUh|ryP MljUV2FPT1KHUh?=
SCLC-21H NHHTOZVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlzrTWM2OD1zLkm3NFU4KM7:TR?= MlXQV2FPT1KHUh?=
GB-1 M1z1OGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHnwT2lKSzVyPUKuNFE3PDdizszN NH3MUlRUSU6JUlXS
KARPAS-45 M3vhNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXXBRYpRUUN3ME2yMlAzPjV2IN88US=> M{XKNXNCVkeURWK=
ATN-1 NGLYbYFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkTsTWM2OD1{LkCyPFU5KM7:TR?= MnqyV2FPT1KHUh?=
NCI-H720 NG\Kc5hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2q0T2lEPTB;Mj6wOlI1PCEQvF2= M{PIPXNCVkeURWK=
RPMI-6666 Mn3uS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVjJNIlFUUN3ME2yMlE3OjB5IN88US=> M{noN3NCVkeURWK=
NB17 NWS5VpBtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEDuZ|BKSzVyPUKuNlkzPyEQvF2= M4DxWnNCVkeURWK=
IST-SL1 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXfJR|UxRTJwMkm3OlUh|ryP NXnidmNNW0GQR2LFVi=>
SH-4 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEnrbGtKSzVyPUKuN|I1PjlizszN NYGzNHJsW0GQR2LFVi=>
K5 MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3TjTWlEPTB;Mj60NFMyQSEQvF2= MkL6V2FPT1KHUh?=
OVCAR-4 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVT0OZIzUUN3ME2yMlQ3OTNizszN MlPIV2FPT1KHUh?=
ACN MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3T5WGlEPTB;Mj61NFIyOyEQvF2= MXjTRW5IWkWU
TGW NX[zTGt[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFzobINKSzVyPUKuOlU5OzJizszN NEKyW29USU6JUlXS
NCI-H2107 MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYTNbZpYUUN3ME2yMlg{PzFzIN88US=> NE\DcmVUSU6JUlXS
NCI-H82 M171XGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVftR|RoUUN3ME2yMlg{QDN6IN88US=> MmfNV2FPT1KHUh?=
SK-N-FI MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYjJR|UxRTJwOE[4Olgh|ryP NHK2UXpUSU6JUlXS
LB1047-RCC M3LwV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mli5TWM2OD1{Lki4NVI3KM7:TR?= MV3TRW5IWkWU
LU-134-A MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MV;JR|UxRTJwOEmyOkDPxE1? MYTTRW5IWkWU
NCI-H209 NWnYSIZPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4P2UmlEPTB;Mj65NVI2OyEQvF2= NHHQSpdUSU6JUlXS
NOMO-1 MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVjJR|UxRTNwMEKyO|Qh|ryP NWqzWWxWW0GQR2LFVi=>
RH-1 MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFvyTYJKSzVyPUOuNVczQTFizszN MUDTRW5IWkWU
LOUCY MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWHJR|UxRTNwMUi2PVMh|ryP NV[3[IlLW0GQR2LFVi=>
TE-9 MlHRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFzjNGhKSzVyPUOuNlY4OzZizszN MXrTRW5IWkWU
PF-382 MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYrJR|UxRTNwM{W3O|gh|ryP MX;TRW5IWkWU
RPMI-8402 MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NESyWo5KSzVyPUOuOVg3ODNizszN NYKwboIxW0GQR2LFVi=>
HEL NYCwd2RYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M17FcGlEPTB;Mz62N|Ih|ryP NVXZ[WV2W0GQR2LFVi=>
NOS-1 NYfpcYk6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVnJR|UxRTNwOES3OVQh|ryP NV7uVVhVW0GQR2LFVi=>
ES1 MoO3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWXrV2l[UUN3ME2zMlkzOjl|IN88US=> MYXTRW5IWkWU
NCI-H2171 M3zFd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEDWSVlKSzVyPUOuPVI1OjNizszN NYfSbopHW0GQR2LFVi=>
NCI-H747 NFrkOHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHHWTmpKSzVyPUOuPVQzOjFizszN NWjObpl2W0GQR2LFVi=>
MHH-NB-11 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUnJR|UxRTNwOUWzNVIh|ryP MV3TRW5IWkWU
MZ1-PC MoTVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWTaZWxsUUN3ME2zMlk6OjRizszN MYrTRW5IWkWU
MMAC-SF NIjJdpBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEfkbHRKSzVyPUSuNFI1PjdizszN MkDyV2FPT1KHUh?=
NMC-G1 NXLtNmdST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlT0TWM2OD12LkKyO|I{KM7:TR?= M3zrWnNCVkeURWK=
SW872 M{LJ[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MoXpTWM2OD12LkO0N|Qh|ryP MXPTRW5IWkWU
TE-12 NXz3bYUzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWPJb3dXUUN3ME20MlU3Ozl2IN88US=> M2\3WHNCVkeURWK=
LU-139 M2CybWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYPvelZ7UUN3ME20MlYyQDN3IN88US=> NHPXcplUSU6JUlXS
HC-1 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWrESWNRUUN3ME20MlY6PDl2IN88US=> NGH2XYVUSU6JUlXS
COR-L279 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MkX3TWM2OD12Lke1PFkyKM7:TR?= M4Oxd3NCVkeURWK=
SF268 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFHofVVKSzVyPUSuO|k6OTZizszN NGjkXolUSU6JUlXS
MC-CAR NEXDRpVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUDobox2UUN3ME21MlA3PzV5IN88US=> NYfJZmFWW0GQR2LFVi=>
TK10 NEj3WHVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlPqTWM2OD13LkO1OFY6KM7:TR?= NH\rUW5USU6JUlXS
TE-1 NGXhVpZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnPiTWM2OD13LkS5NFA1KM7:TR?= MXvTRW5IWkWU
NCI-H2126 M2OyVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXPtXHI{UUN3ME21MlY1PTd2IN88US=> MkC5V2FPT1KHUh?=
Daudi NFfhepZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV7JR|UxRTVwNkmxNkDPxE1? NUDTU5dkW0GQR2LFVi=>
NCI-H1648 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmXwTWM2OD13LkixOFU1KM7:TR?= MYrTRW5IWkWU
OS-RC-2 NXPoWlk2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIK4dW1KSzVyPUWuPVg2QTdizszN NH3EU|lUSU6JUlXS
DJM-1 M4Pn[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYDJR|UxRTZwM{S2OlYh|ryP NXLBVVZbW0GQR2LFVi=>
LS-1034 NHzKfHdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFn5SXZKSzVyPU[uO|U3PiEQvF2= NFXoUYNUSU6JUlXS
NCI-H1581 MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV\CeZc3UUN3ME22Mlc5PDB3IN88US=> MYTTRW5IWkWU
UACC-257 NGnYbG9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXrJR|UxRTdwMES1NVIh|ryP M4LYUXNCVkeURWK=
KM-H2 NYn6NFZLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mn\5TWM2OD15LkG4OFU4KM7:TR?= NInlcmNUSU6JUlXS
NCI-H1436 NHrs[GJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3znZWlEPTB;Nz62PVk{OiEQvF2= M2H1VnNCVkeURWK=
IA-LM MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{TndmlEPTB;Nz64OVkh|ryP NYnVOll7W0GQR2LFVi=>
NCI-H526 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXvJR|UxRThwMkW2N|ch|ryP MUXTRW5IWkWU
GCIY MmrFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mof4TWM2OD16LkO2PVY2KM7:TR?= NYjXVnVRW0GQR2LFVi=>
CP67-MEL MkHRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVXSbI8{UUN3ME24MlU{OjZizszN M{Cw[nNCVkeURWK=
KALS-1 NUf2b5pJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX3B[|ZFUUN3ME24Mlg{QDVzIN88US=> NYX6bHVuW0GQR2LFVi=>
NCI-H1770 MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF;2fWlKSzVyPUiuPVAzPjVizszN MXzTRW5IWkWU
8-MG-BA M2rpemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NELPb|hKSzVyPUmuN|I5PDRizszN NEfF[Y9USU6JUlXS
KY821 M2fiRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUTJR|UxRTlwN{e0PFQh|ryP NH3LSYNUSU6JUlXS
SNB75 NUW2dJVMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3zMTGlEPTB;MUCuNFc3KM7:TR?= MYTTRW5IWkWU
NCCIT M2LCemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUfJR|UxRTFzLkC1PFIh|ryP NYXZXVNwW0GQR2LFVi=>
SJSA-1 NVvi[lVPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NI\ob3ZKSzVyPUGxMlI5QTFizszN NH2wbnBUSU6JUlXS
LB373-MEL-D MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV7OV5c6UUN3ME2xNU4{QDJ5IN88US=> NVTERVh[W0GQR2LFVi=>
TALL-1 NVj0R29JT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHzpenJKSzVyPUGxMlQxPThizszN NGO5XoZUSU6JUlXS
NB69 NH7IZ4JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWXJR|UxRTFzLke3NFUh|ryP M4\pVHNCVkeURWK=
NCI-H1355 MlTzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX\RV2F4UUN3ME2xNU46PDJ4IN88US=> NFTB[HdUSU6JUlXS
DMS-153 MmXrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NW\l[VRGUUN3ME2xNk4xPDJ4IN88US=> MUHTRW5IWkWU
OPM-2 Ml7RS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MULJR|UxRTF{LkG1PVYh|ryP Mli3V2FPT1KHUh?=
NB1 MnTlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXzEcItWUUN3ME2xNk4zQSEQvF2= MXXTRW5IWkWU
A3-KAW NVjST2NvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXXlXWN{UUN3ME2xNk4{OjN4IN88US=> Ml;zV2FPT1KHUh?=
NCI-H1882 MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnTRTWM2OD1zMj60NFY3KM7:TR?= M3HBd3NCVkeURWK=
KG-1 NUT4bo5lT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVfJR|UxRTF{Lk[1OFUh|ryP M4jv[3NCVkeURWK=
LC4-1 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4L1bWlEPTB;MUKuO|cxPiEQvF2= NHXpU5RUSU6JUlXS
HCE-T NUP0bIg{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NVX2O417UUN3ME2xN{4xODR7IN88US=> NIi4UVhUSU6JUlXS
NEC8 MlP4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGDrVJVKSzVyPUGzMlExOzhizszN NHfJemhUSU6JUlXS
IST-MEL1 MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF7nPFVKSzVyPUGzMlU4QDhizszN MVPTRW5IWkWU
EW-3 MmjkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYPvUnBCUUN3ME2xN{44PDB{IN88US=> NX7HN|M2W0GQR2LFVi=>
CTB-1 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGPSVVFKSzVyPUG0MlA{OjlizszN NXS2OmZZW0GQR2LFVi=>
LS-123 NFi1NY5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2naWmlEPTB;MUSuNVU5QCEQvF2= NVKwXmpxW0GQR2LFVi=>
NCI-H1417 NWHyelZyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mk\ZTWM2OD1zND6zNFUzKM7:TR?= NUHSeVBOW0GQR2LFVi=>
MZ7-mel MlXNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIjq[4lKSzVyPUG0MlQ1OzNizszN NGXieGRUSU6JUlXS
JiyoyeP-2003 NG\hVHVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV\JR|UxRTF3Lk[zNlYh|ryP Mn:3V2FPT1KHUh?=
ES6 NUnJdGl4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYLJR|UxRTF4LkKzOlEh|ryP NGjTSXNUSU6JUlXS
HH NGL0NnpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4jrbGlEPTB;MUeuNVk3OyEQvF2= MmLqV2FPT1KHUh?=
SF539 M3rMOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1HUUmlEPTB;MUeuPVkzOiEQvF2= NYPIZYMyW0GQR2LFVi=>
Calu-6 MnjlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MojDTWM2OD1zOT6yN|kh|ryP M1z6V3NCVkeURWK=
SK-MM-2 MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NETw[|lKSzVyPUG5MlU2PSEQvF2= MYPTRW5IWkWU
IST-MES1 NHLpVZhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MofGTWM2OD1zOT62OlY{KM7:TR?= NWnFVHQ5W0GQR2LFVi=>
GI-ME-N M{O3OWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkTiTWM2OD1zOT64NlI4KM7:TR?= NF3ZemNUSU6JUlXS
CAL-148 MnHJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlTSTWM2OD1{MD65PVM1KM7:TR?= NFXD[I1USU6JUlXS
EVSA-T M2CyeGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEjaUmVKSzVyPUKxMlE1QTlizszN Ml7kV2FPT1KHUh?=
LP-1 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NHuyV45KSzVyPUKxMlM1OzJizszN Ml3EV2FPT1KHUh?=
BOKU MoTvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYXxT3F5UUN3ME2yNU41PTN|IN88US=> M4jnUHNCVkeURWK=
KLE M1\MXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYTJR|UxRTJ{LkG5NFMh|ryP MUTTRW5IWkWU
LB831-BLC NUTle5lRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHS0XlhKSzVyPUK1MlE2OjZizszN NUHpUnZ7W0GQR2LFVi=>
NCI-H889 NV;oeJkyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{XWUmlEPTB;MkWuNVk{OSEQvF2= NYLleoJLW0GQR2LFVi=>
REH NX7PRYlVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3HrUWlEPTB;MkWuOFY4OSEQvF2= NYPTXXc6W0GQR2LFVi=>
KP-N-RT-BM-1 NETwcIVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVS2Tm54UUN3ME2yOU41PzV{IN88US=> M4L4bHNCVkeURWK=
MPP-89 MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYP3cXZIUUN3ME2yOU42OzF2IN88US=> NFjoXnhUSU6JUlXS
no-11 NFLNNlJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3zZNWlEPTB;MkWuO|Q4KM7:TR?= M1zmc3NCVkeURWK=
NCI-H748 Mn\tS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2TEWGlEPTB;MkWuO|YzPyEQvF2= NGrOTWFUSU6JUlXS
LB2518-MEL MnLJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1\rWGlEPTB;MkeuNVc4OyEQvF2= MnvwV2FPT1KHUh?=
TGBC1TKB MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGnlVIxKSzVyPUK3MlU2QDVizszN NXzMZoJKW0GQR2LFVi=>
MHH-PREB-1 M1HudGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmSxTWM2OD1{OD6wO|M1KM7:TR?= MWnTRW5IWkWU
MZ2-MEL NIH2SpdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MV\JR|UxRTJ6Lk[xOFMh|ryP NW[1[mZRW0GQR2LFVi=>
U-266 NFLGSGRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGewR45KSzVyPUK4MlY{PjZizszN MUXTRW5IWkWU
SNU-C1 NHe1dGZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXXJR|UxRTJ6Lkm0N{DPxE1? NYP0OoRpW0GQR2LFVi=>
SW962 MnTmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYf1bnFDUUN3ME2zNE4zPzR5IN88US=> MUPTRW5IWkWU
Raji NUnsSYk6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYLJR|UxRTNyLkW1PVIh|ryP MYTTRW5IWkWU
KNS-42 M4LZVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MV\JR|UxRTNyLki5OVYh|ryP NFfme4NUSU6JUlXS
LB996-RCC Ml\tS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3XqTmlEPTB;M{GuNVcxOiEQvF2= MoroV2FPT1KHUh?=
CHP-126 M4rSZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{XDU2lEPTB;M{GuNVk5PCEQvF2= M{mzNnNCVkeURWK=
RXF393 MnLwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn3uTWM2OD1|Mj60PVch|ryP NFL6dHZUSU6JUlXS
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KNS-81-FD M4LlRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4SzNGlEPTB;M{SuOVQ2PiEQvF2= M3LC[HNCVkeURWK=
TE-441-T NWH0ZmJoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYezVmw1UUN3ME2zOE43OzdzIN88US=> NGnMSVdUSU6JUlXS
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ES3 M33YTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1;2VWlEPTB;M{[uOlc2KM7:TR?= M1GzfXNCVkeURWK=
NCI-H1155 MorZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYHJR|UxRTN5LkixOUDPxE1? M1rRWXNCVkeURWK=
SNU-C2B MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVvnVG9DUUN3ME2zPE4yPjV2IN88US=> MYHTRW5IWkWU
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GDM-1 NXrBToE1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NY\aNpBXUUN3ME2zPE46OTF4IN88US=> NEP2e|hUSU6JUlXS
KU812 M1:xXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUD6O5dWUUN3ME20NU42ODdizszN M1f0XXNCVkeURWK=
BC-1 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3[4UWlEPTB;NEKuOlc{OSEQvF2= NFTlV4FUSU6JUlXS
GI-1 MorwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4rFNWlEPTB;NEKuPVE6OiEQvF2= MljBV2FPT1KHUh?=
NCI-H1694 M3;Xb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1\zbmlEPTB;NESuPVQ4OiEQvF2= MofTV2FPT1KHUh?=
DG-75 NXvBfGJ6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHXOTlhKSzVyPUS1MlE2PzdizszN M2rBWXNCVkeURWK=
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LS-513 M3\ZN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MXXJR|UxRTR3LkmxOVYh|ryP NVjUcJRmW0GQR2LFVi=>
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L-363 M3[2Vmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWXUWlk{UUN3ME20Ok45QDFizszN NU\tcWFGW0GQR2LFVi=>
TE-6 MnfhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYnNOY9mUUN3ME20PE41PDZizszN NXv3TJFXW0GQR2LFVi=>
NCI-H345 M3PPO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGDMZXFKSzVyPUS4MlQ3QCEQvF2= NYTZPGVVW0GQR2LFVi=>
TE-5 M1v0d2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHLmVnRKSzVyPUS5MlcyOThizszN NYHrfXRNW0GQR2LFVi=>

... 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