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 Mnn5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGPPN4hKSzVyPUCuNFA{OzhizszN Mk\qV2FPT1KHUh?=
RS4-11 M{SyRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmjUTWM2OD1yLkCwOFA1KM7:TR?= NX\iRoF1W0GQR2LFVi=>
MFH-ino M4LFd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXm3SoE4UUN3ME2wMlAxQTlizszN MorRV2FPT1KHUh?=
NTERA-S-cl-D1 MoP4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M2fIb2lEPTB;MD6wNVQ{PCEQvF2= MWLTRW5IWkWU
697 NXWwZWJkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFnjVHBKSzVyPUCuNFI1PzFizszN NFzVTXRUSU6JUlXS
NALM-6 MlzLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnnhTWM2OD1yLkCyOVUzKM7:TR?= MYTTRW5IWkWU
ES8 NEDDRWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3iwU2lEPTB;MD6wOFYyOyEQvF2= M1K5e3NCVkeURWK=
HUTU-80 NWrjW|U{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVnJR|UxRTBwMEWyPVkh|ryP MkjCV2FPT1KHUh?=
MV-4-11 NUj3emVDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlvzTWM2OD1yLkC3O|gzKM7:TR?= NHrXVYtUSU6JUlXS
MONO-MAC-6 NXP4SnROT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEjHdmVKSzVyPUCuNFc5PzlizszN MXfTRW5IWkWU
LC-2-ad M33Me2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Mn7GTWM2OD1yLkC4O|g6KM7:TR?= MoXpV2FPT1KHUh?=
BL-41 M4DsN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2TYNmlEPTB;MD6xNFQ1PSEQvF2= NF:1[IdUSU6JUlXS
A4-Fuk MmDkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3mz[GlEPTB;MD6xNVU3OyEQvF2= MmfaV2FPT1KHUh?=
SW954 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEC4XmZKSzVyPUCuNVIzOjlizszN NGjkT4xUSU6JUlXS
BV-173 MmjuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWnJR|UxRTBwMUK2OFEh|ryP M3rJdHNCVkeURWK=
TE-11 MnPZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlPhTWM2OD1yLkG0PVgzKM7:TR?= MWPTRW5IWkWU
SK-UT-1 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M170c2lEPTB;MD6xOVk3PSEQvF2= NHy2XGlUSU6JUlXS
SIG-M5 MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2DtPWlEPTB;MD6xOlcxPyEQvF2= MX3TRW5IWkWU
OCUB-M M{fkW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MofSTWM2OD1yLkG2PVg{KM7:TR?= M13tdHNCVkeURWK=
K052 MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFPqRmJKSzVyPUCuNVk1QCEQvF2= NWTte|lCW0GQR2LFVi=>
VA-ES-BJ MkTQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXvLV4RNUUN3ME2wMlIxODh4IN88US=> MUHTRW5IWkWU
SW982 MkLUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVjJR|UxRTBwMkGzPEDPxE1? Ml7vV2FPT1KHUh?=
LB647-SCLC MmrGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml\PTWM2OD1yLkKxOVI{KM7:TR?= NXfKSGxPW0GQR2LFVi=>
PSN1 NIrLeFlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYfJR|UxRTBwMkKwNlYh|ryP NFG0b2dUSU6JUlXS
BB30-HNC NHPHSJpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHXnXWdKSzVyPUCuNlI2QTFizszN MmjEV2FPT1KHUh?=
ST486 MnjPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NHPYeJhKSzVyPUCuNlMxQDdizszN Mmm0V2FPT1KHUh?=
MOLT-4 MlzlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYDrZ5ZQUUN3ME2wMlI{OzN5IN88US=> MX7TRW5IWkWU
EW-16 MljOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlLmTWM2OD1yLkKzO|Y5KM7:TR?= M17vW3NCVkeURWK=
KS-1 NEjnfmRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH;0c3VKSzVyPUCuNlM4QDVizszN MoG1V2FPT1KHUh?=
SR NXTWO21GT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnXrTWM2OD1yLkK0OVY1KM7:TR?= NIDVV3hUSU6JUlXS
KM12 NFT2T4JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVPJR|UxRTBwMk[zOkDPxE1? NYDk[YtHW0GQR2LFVi=>
EM-2 M1vIWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 Ml3yTWM2OD1yLkK2OlQyKM7:TR?= MmfnV2FPT1KHUh?=
MEG-01 M12zUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVP4coJTUUN3ME2wMlI4QDR7IN88US=> NVXYUHlPW0GQR2LFVi=>
NB13 NILLfIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M{faTmlEPTB;MD6yO|k5PCEQvF2= MV3TRW5IWkWU
RKO MlTFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4naRmlEPTB;MD6zNFgyOyEQvF2= MVvTRW5IWkWU
CESS MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWrQPZVFUUN3ME2wMlMyOzJ6IN88US=> M2Pvb3NCVkeURWK=
EoL-1-cell NYfDV2JmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUnJR|UxRTBwM{O0OVkh|ryP MmTzV2FPT1KHUh?=
DOHH-2 MlT0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml:2TWM2OD1yLkOzO|gyKM7:TR?= NILIdIlUSU6JUlXS
A388 NFryW2JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYX1WWNFUUN3ME2wMlM1ODh4IN88US=> MW\TRW5IWkWU
LAMA-84 NEHWWo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M13yZWlEPTB;MD6zOVE4QCEQvF2= M3;IenNCVkeURWK=
IMR-5 MlTkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWi2RlJRUUN3ME2wMlM2PTRizszN NEXiR3VUSU6JUlXS
KARPAS-422 NXnKcIJbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYrJR|UxRTBwM{eyO|Ih|ryP Mn3rV2FPT1KHUh?=
MRK-nu-1 NIHTbZZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NYn3WlduUUN3ME2wMlM5OTNizszN M3TnXnNCVkeURWK=
BL-70 MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYDJR|UxRTBwM{i5O|Qh|ryP MWPTRW5IWkWU
LXF-289 M2PFfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXLRbW01UUN3ME2wMlQxPDB4IN88US=> NEDydVlUSU6JUlXS
RL95-2 Mor6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NIrHNYdKSzVyPUCuOFA2PjdizszN NXjGd2ZUW0GQR2LFVi=>
QIMR-WIL M2Djbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{Tq[mlEPTB;MD60NlY4PiEQvF2= MWPTRW5IWkWU
K-562 MlvHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXrJR|UxRTBwNEO0O|Ih|ryP Ml64V2FPT1KHUh?=
NCI-H510A MmTyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3P5NGlEPTB;MD60N|gzOyEQvF2= MnvOV2FPT1KHUh?=
NCI-H524 Ml;uS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M33ObGlEPTB;MD61NVE1PyEQvF2= NE\iSW9USU6JUlXS
KE-37 M163XGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX3JR|UxRTBwNUKxNFIh|ryP NHfadGtUSU6JUlXS
KP-N-YS M1f3Umdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M4HqdGlEPTB;MD61OFM6OiEQvF2= M{G1T3NCVkeURWK=
LS-411N MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFfxU2tKSzVyPUCuOVc4PTJizszN MmfmV2FPT1KHUh?=
CTV-1 NGfrWnZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHrkWZhKSzVyPUCuOVg4PzNizszN M4HTRXNCVkeURWK=
NCI-SNU-16 Mli1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmK3TWM2OD1yLk[zOVcyKM7:TR?= NEf3UXJUSU6JUlXS
HT-144 MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NEfzSWRKSzVyPUCuOlM4QThizszN MVjTRW5IWkWU
NCI-H187 MoTsS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M4PZdmlEPTB;MD62OFE{KM7:TR?= MYHTRW5IWkWU
OCI-AML2 NIPD[mhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWXZ[FZpUUN3ME2wMlY1PDB|IN88US=> MX7TRW5IWkWU
CCRF-CEM NXTqXYFRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4HJZ2lEPTB;MD62OVM1PiEQvF2= M2L6[HNCVkeURWK=
ONS-76 MnTnS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFuyeGNKSzVyPUCuOlY1PThizszN MnXiV2FPT1KHUh?=
IST-SL2 MlrMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEf6TnJKSzVyPUCuO|E6QDJizszN NHnCN2FUSU6JUlXS
NB6 M1P2UGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFXxVWVKSzVyPUCuO|czPTRizszN NVi2c4E{W0GQR2LFVi=>
SK-PN-DW M{XGPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NFvYPZdKSzVyPUCuO|kyPCEQvF2= NVjaOIdyW0GQR2LFVi=>
HCC1599 NYDXTIpDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{nNWmlEPTB;MD64NFg4PCEQvF2= M1HNeXNCVkeURWK=
MC116 NH3NSGRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1f0TGlEPTB;MD64OVAyOSEQvF2= NGHCTHhUSU6JUlXS
TE-15 NUmzcm4yT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYHJR|UxRTBwOEWwPVgh|ryP M{D3W3NCVkeURWK=
HOP-62 M3\4[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXztPHdzUUN3ME2wMlg3OzJ7IN88US=> MWnTRW5IWkWU
TGBC24TKB NXXUNFl4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYDJR|UxRTBwOE[zPFUh|ryP M3TmbHNCVkeURWK=
HCE-4 MmLxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXHDWWFrUUN3ME2wMlg5ODZ|IN88US=> MV\TRW5IWkWU
ALL-PO MorCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NF7YNYhKSzVyPUCuPFgyPzVizszN NXS0bnpFW0GQR2LFVi=>
KGN M1ewb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYfhUYNQUUN3ME2wMlg6QTl3IN88US=> MXPTRW5IWkWU
ML-2 Mn\uS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGfFOYZKSzVyPUCuPVAzPTlizszN NEPPeVJUSU6JUlXS
ES4 MnK4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NU\MVnB5UUN3ME2wMlkyOTJ6IN88US=> NGroNohUSU6JUlXS
SF126 MkDzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVHtSJpqUUN3ME2wMlk1QDF7IN88US=> M2izOXNCVkeURWK=
SK-N-DZ M4L4Wmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYPJR|UxRTBwOU[xPFkh|ryP NWHXOlRKW0GQR2LFVi=>
HCC1187 NETw[nRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYDJR|UxRTFwMEC1NFUh|ryP MVHTRW5IWkWU
DU-4475 NYi2TXhzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXfJR|UxRTFwMEG3OVYh|ryP MUPTRW5IWkWU
NKM-1 M1vLVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1HXbmlEPTB;MT6wNlc4PSEQvF2= MkHZV2FPT1KHUh?=
HL-60 M3vNSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmTVTWM2OD1zLkC2OVc1KM7:TR?= MWXTRW5IWkWU
SBC-1 MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NF\LR|BKSzVyPUGuNVI2PDJizszN NYm4eWZ{W0GQR2LFVi=>
TE-10 MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVjJR|UxRTFwMUK5OFYh|ryP M3nCcnNCVkeURWK=
ETK-1 M2raT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3HWOWlEPTB;MT6xN|YyOyEQvF2= NWPRPGQ5W0GQR2LFVi=>
HAL-01 NIm1eJlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX:zSlRJUUN3ME2xMlE3PzB7IN88US=> NHO2V4VUSU6JUlXS
BB65-RCC MmDTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MW\JR|UxRTFwMUiwNFUh|ryP MYrTRW5IWkWU
EW-1 MoHhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml:zTWM2OD1zLkG4OVYzKM7:TR?= M1TrWnNCVkeURWK=
SK-NEP-1 M{HoN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEPBN5JKSzVyPUGuNlEyOTFizszN M1ruTHNCVkeURWK=
SK-LMS-1 MkTDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYjJR|UxRTFwMkKyNVIh|ryP MkG1V2FPT1KHUh?=
DEL Mme3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVvJR|UxRTFwMkW2OFMh|ryP NFrNe|RUSU6JUlXS
GT3TKB Moj0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYLYdnZrUUN3ME2xMlI5ODV5IN88US=> NYnRdYkxW0GQR2LFVi=>
MOLT-16 NULJfWV1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M17CTmlEPTB;MT6zOVQxPSEQvF2= MXnTRW5IWkWU
CMK MmG3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVvmfGtRUUN3ME2xMlQzOTF5IN88US=> MYPTRW5IWkWU
NB5 MnjpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MkCwTWM2OD1zLk[0NlI6KM7:TR?= NFmzcGJUSU6JUlXS
NCI-H1963 NVu0PGVvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MojhTWM2OD1zLkewOVg{KM7:TR?= NUDUOYNuW0GQR2LFVi=>
KURAMOCHI M2jDNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYTJR|UxRTFwN{i5NVEh|ryP NIOzRZlUSU6JUlXS
TE-8 M{\LU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYHJR|UxRTFwOECzOlgh|ryP MlHZV2FPT1KHUh?=
NCI-H1304 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NUDSUZF[UUN3ME2xMlg{ODd|IN88US=> M3T3N3NCVkeURWK=
A101D NVL4N4t[T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF;CcHpKSzVyPUGuPFc{QTVizszN MUnTRW5IWkWU
SCLC-21H M3fHUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnPTTWM2OD1zLkm3NFU4KM7:TR?= MorqV2FPT1KHUh?=
GB-1 NETZdWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3ywR2lEPTB;Mj6wNVY1PyEQvF2= M3fEPHNCVkeURWK=
KARPAS-45 MoO1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3vpUWlEPTB;Mj6wNlY2PCEQvF2= MWXTRW5IWkWU
ATN-1 M{fic2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVG5N4JKUUN3ME2yMlAzQDV6IN88US=> NXjMW|hXW0GQR2LFVi=>
NCI-H720 NFzXbZpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFj2[FJKSzVyPUKuNFYzPDRizszN MUfTRW5IWkWU
RPMI-6666 Mmj5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1HCR2lEPTB;Mj6xOlIxPyEQvF2= M374WnNCVkeURWK=
NB17 NIO2SHFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkHvTWM2OD1{LkK5Nlch|ryP M1LZUXNCVkeURWK=
IST-SL1 NVjQcWhlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIX1b2NKSzVyPUKuNlk4PjVizszN NVvZcIRkW0GQR2LFVi=>
SH-4 NV3JSo1TT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVPJR|UxRTJwM{K0Olkh|ryP NI[4bHlUSU6JUlXS
K5 MlLlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3f3PWlEPTB;Mj60NFMyQSEQvF2= MoDBV2FPT1KHUh?=
OVCAR-4 M{DqcWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIPESoZKSzVyPUKuOFYyOyEQvF2= MU\TRW5IWkWU
ACN NYLBUGIyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M{PBTmlEPTB;Mj61NFIyOyEQvF2= NXq5OGpMW0GQR2LFVi=>
TGW NIG3XnlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mn;mTWM2OD1{Lk[1PFMzKM7:TR?= Mn7CV2FPT1KHUh?=
NCI-H2107 NEDj[3ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1LXOWlEPTB;Mj64N|cyOSEQvF2= MVrTRW5IWkWU
NCI-H82 MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVvJR|UxRTJwOEO4N|gh|ryP MkjOV2FPT1KHUh?=
SK-N-FI MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVzJR|UxRTJwOE[4Olgh|ryP M1HHSXNCVkeURWK=
LB1047-RCC Mn20S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1TJOGlEPTB;Mj64PFEzPiEQvF2= MmHzV2FPT1KHUh?=
LU-134-A NGHmcVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEfmTYhKSzVyPUKuPFkzPiEQvF2= NXGwTW5uW0GQR2LFVi=>
NCI-H209 MlvmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEXPTFVKSzVyPUKuPVEzPTNizszN M4T3bHNCVkeURWK=
NOMO-1 NV33O5dOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlfmTWM2OD1|LkCyNlc1KM7:TR?= MnHiV2FPT1KHUh?=
RH-1 NVHiXY1sT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlXaTWM2OD1|LkG3NlkyKM7:TR?= NUnKWVJSW0GQR2LFVi=>
LOUCY MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M13FXWlEPTB;Mz6xPFY6OyEQvF2= NXX4d4NEW0GQR2LFVi=>
TE-9 M2HvWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M{HUOWlEPTB;Mz6yOlc{PiEQvF2= NFfvfG1USU6JUlXS
PF-382 Mnv5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M33ITWlEPTB;Mz6zOVc4QCEQvF2= M4ro[XNCVkeURWK=
RPMI-8402 NWr5VYg5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGfpUJFKSzVyPUOuOVg3ODNizszN NHzjSWJUSU6JUlXS
HEL NXr1dGd3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3u0[WlEPTB;Mz62N|Ih|ryP NX;RXHlmW0GQR2LFVi=>
NOS-1 NVXCZlc5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M1TTO2lEPTB;Mz64OFc2PCEQvF2= NVLMeFRvW0GQR2LFVi=>
ES1 MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{jHPGlEPTB;Mz65NlI6OyEQvF2= NXjzUpBSW0GQR2LFVi=>
NCI-H2171 MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFzCXnZKSzVyPUOuPVI1OjNizszN NVSyR2pvW0GQR2LFVi=>
NCI-H747 NELOU|dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MkL0TWM2OD1|Lkm0NlIyKM7:TR?= MoX0V2FPT1KHUh?=
MHH-NB-11 MnTwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1;QO2lEPTB;Mz65OVMyOiEQvF2= Mnv2V2FPT1KHUh?=
MZ1-PC MmL3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYHJR|UxRTNwOUmyOEDPxE1? MVHTRW5IWkWU
MMAC-SF NH\RWHBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NFnoe3ZKSzVyPUSuNFI1PjdizszN NGrFWIFUSU6JUlXS
NMC-G1 MmHxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3zic2lEPTB;ND6yNlczOyEQvF2= M3TBfnNCVkeURWK=
SW872 NF3HOWZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MlfTTWM2OD12LkO0N|Qh|ryP NYDyXWhZW0GQR2LFVi=>
TE-12 NID1ToZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NV7BeYkyUUN3ME20MlU3Ozl2IN88US=> NH7IVpBUSU6JUlXS
LU-139 MkXKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYPXRnRzUUN3ME20MlYyQDN3IN88US=> MYfTRW5IWkWU
HC-1 MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4HTbWlEPTB;ND62PVQ6PCEQvF2= MVzTRW5IWkWU
COR-L279 Mm[wS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NILVcXpKSzVyPUSuO|U5QTFizszN M2nZNXNCVkeURWK=
SF268 NVKzSXMyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NULN[HFuUUN3ME20Mlc6QTF4IN88US=> NIr1cYVUSU6JUlXS
MC-CAR MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3:yWWlEPTB;NT6wOlc2PyEQvF2= Mom2V2FPT1KHUh?=
TK10 NF3UO3JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWDJR|UxRTVwM{W0Olkh|ryP NH7GdJFUSU6JUlXS
TE-1 MnzPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUHJR|UxRTVwNEmwNFQh|ryP NX7Hb5l7W0GQR2LFVi=>
NCI-H2126 M4DZUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NUPkXZdKUUN3ME21MlY1PTd2IN88US=> MX\TRW5IWkWU
Daudi MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmL4TWM2OD13Lk[5NVIh|ryP MnHlV2FPT1KHUh?=
NCI-H1648 NILlb5NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWPJR|UxRTVwOEG0OVQh|ryP M{\RUHNCVkeURWK=
OS-RC-2 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFu0WFZKSzVyPUWuPVg2QTdizszN MVvTRW5IWkWU
DJM-1 M2nQS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYfJR|UxRTZwM{S2OlYh|ryP MX;TRW5IWkWU
LS-1034 NVT4OIk2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MX;JR|UxRTZwN{W2OkDPxE1? NHXHbo1USU6JUlXS
NCI-H1581 NGrlbWtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NX3MWYRqUUN3ME22Mlc5PDB3IN88US=> MlHVV2FPT1KHUh?=
UACC-257 M{PpdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MVPJR|UxRTdwMES1NVIh|ryP NIPmSW1USU6JUlXS
KM-H2 MoWxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NH3UfIdKSzVyPUeuNVg1PTdizszN MnqzV2FPT1KHUh?=
NCI-H1436 Ml7US5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoHDTWM2OD15Lk[5PVMzKM7:TR?= NGTqfldUSU6JUlXS
IA-LM NVLq[pVuT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2TpTWlEPTB;Nz64OVkh|ryP Mk\zV2FPT1KHUh?=
NCI-H526 Mnm3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXfJR|UxRThwMkW2N|ch|ryP NXXPd|JPW0GQR2LFVi=>
GCIY MlH3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3\5PWlEPTB;OD6zOlk3PSEQvF2= M2T5RXNCVkeURWK=
CP67-MEL MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NGjVTYlKSzVyPUiuOVMzPiEQvF2= NF:5PIpUSU6JUlXS
KALS-1 NX3VWpRpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX\SdHhIUUN3ME24Mlg{QDVzIN88US=> M2f1U3NCVkeURWK=
NCI-H1770 MnjBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NX71T2dKUUN3ME24MlkxOjZ3IN88US=> Mo\rV2FPT1KHUh?=
8-MG-BA NEjN[XpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NELB[ItKSzVyPUmuN|I5PDRizszN M1fTWXNCVkeURWK=
KY821 NGjqSFNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUDLT4ZyUUN3ME25Mlc4PDh2IN88US=> MoDGV2FPT1KHUh?=
SNB75 NVvTNI54T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGTKTVZKSzVyPUGwMlA4PiEQvF2= M2Xnd3NCVkeURWK=
NCCIT MmWxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWjJR|UxRTFzLkC1PFIh|ryP M3n4WXNCVkeURWK=
SJSA-1 M17QXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M3e2bGlEPTB;MUGuNlg6OSEQvF2= M{XBS3NCVkeURWK=
LB373-MEL-D MlPzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NXTqbmtYUUN3ME2xNU4{QDJ5IN88US=> MWDTRW5IWkWU
TALL-1 M2fs[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYnJR|UxRTFzLkSwOVgh|ryP NVq0eoZlW0GQR2LFVi=>
NB69 NFrNOm5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX\JR|UxRTFzLke3NFUh|ryP MX\TRW5IWkWU
NCI-H1355 M1q1R2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NGnmXotKSzVyPUGxMlk1OjZizszN Mnf5V2FPT1KHUh?=
DMS-153 Mlm4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWDJR|UxRTF{LkC0NlYh|ryP M4nIT3NCVkeURWK=
OPM-2 MnHyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NYnNZ|dTUUN3ME2xNk4yPTl4IN88US=> NYS2dY51W0GQR2LFVi=>
NB1 NF\1cXdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M160UmlEPTB;MUKuNlkh|ryP NXPPfGRuW0GQR2LFVi=>
A3-KAW NFuydlBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXvJR|UxRTF{LkOyN|Yh|ryP MXvTRW5IWkWU
NCI-H1882 NI\LOJJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWDJR|UxRTF{LkSwOlYh|ryP M4i2S3NCVkeURWK=
KG-1 NHzTfHVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4DsWmlEPTB;MUKuOlU1PSEQvF2= M1nYSnNCVkeURWK=
LC4-1 NXPscVN5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXPTc2VpUUN3ME2xNk44PzB4IN88US=> NW\jeXFwW0GQR2LFVi=>
HCE-T NY\JVWxmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mlq5TWM2OD1zMz6wNFQ6KM7:TR?= NI\2coxUSU6JUlXS
NEC8 M{HUVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHTW[mNKSzVyPUGzMlExOzhizszN MX\TRW5IWkWU
IST-MEL1 NIjFOJNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVjJR|UxRTF|LkW3PFgh|ryP NH\hWHhUSU6JUlXS
EW-3 M1\wTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MUXJR|UxRTF|Lke0NFIh|ryP M{HOPHNCVkeURWK=
CTB-1 NH22enNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYLJR|UxRTF2LkCzNlkh|ryP NYKzSJpRW0GQR2LFVi=>
LS-123 NFLGcHBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M3LOSGlEPTB;MUSuNVU5QCEQvF2= M2nPc3NCVkeURWK=
NCI-H1417 M4fPeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXjvc2FGUUN3ME2xOE4{ODV{IN88US=> M4HnPHNCVkeURWK=
MZ7-mel NVu0NZFXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHzJU29KSzVyPUG0MlQ1OzNizszN MmnhV2FPT1KHUh?=
JiyoyeP-2003 MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWTBe2oyUUN3ME2xOU43OzJ4IN88US=> NUj5N2lQW0GQR2LFVi=>
ES6 M1fZ[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NHrFd|NKSzVyPUG2MlI{PjFizszN MXvTRW5IWkWU
HH MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFWwTmRKSzVyPUG3MlE6PjNizszN NHG3XldUSU6JUlXS
SF539 NF;Vb3hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MXfJR|UxRTF5Lkm5NlIh|ryP NVj4TVBPW0GQR2LFVi=>
Calu-6 NFzlZW9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVi1[YRDUUN3ME2xPU4zOzlizszN Ml3pV2FPT1KHUh?=
SK-MM-2 NH7rNlRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M1X1fmlEPTB;MUmuOVU2KM7:TR?= M13QZXNCVkeURWK=
IST-MES1 NEDPb4RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M4jPNWlEPTB;MUmuOlY3OyEQvF2= NEPFN4xUSU6JUlXS
GI-ME-N M2nr[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnPTTWM2OD1zOT64NlI4KM7:TR?= NF3LV|ZUSU6JUlXS
CAL-148 MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NV;ze3VPUUN3ME2yNE46QTN2IN88US=> NVKwT2ZZW0GQR2LFVi=>
EVSA-T NFPEc2dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX7JR|UxRTJzLkG0PVkh|ryP MUDTRW5IWkWU
LP-1 MXLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnHPTWM2OD1{MT6zOFMzKM7:TR?= MV3TRW5IWkWU
BOKU MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MnfTTWM2OD1{MT60OVM{KM7:TR?= MWHTRW5IWkWU
KLE MlyxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MlS3TWM2OD1{Mj6xPVA{KM7:TR?= NX34S3hoW0GQR2LFVi=>
LB831-BLC MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYDJR|UxRTJ3LkG1NlYh|ryP MoDXV2FPT1KHUh?=
NCI-H889 MmPJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NG\2THVKSzVyPUK1MlE6OzFizszN MWLTRW5IWkWU
REH MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmDkTWM2OD1{NT60OlcyKM7:TR?= NYrNSJV7W0GQR2LFVi=>
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MPP-89 MkftS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVnJV3VIUUN3ME2yOU42OzF2IN88US=> M4S2W3NCVkeURWK=
no-11 NWXQWm1NT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFfPc2JKSzVyPUK1Mlc1PyEQvF2= MmHGV2FPT1KHUh?=
NCI-H748 MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MXrJR|UxRTJ3Lke2Nlch|ryP NILMbYVUSU6JUlXS
LB2518-MEL MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NXXqVJpPUUN3ME2yO{4yPzd|IN88US=> M{\NfnNCVkeURWK=
TGBC1TKB NHP1U3NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUHySFBsUUN3ME2yO{42PTh3IN88US=> NGDzb5FUSU6JUlXS
MHH-PREB-1 M3ezT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M2LKeGlEPTB;MkiuNFc{PCEQvF2= MnO4V2FPT1KHUh?=
MZ2-MEL MlviS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NFe0WJpKSzVyPUK4MlYyPDNizszN MmXnV2FPT1KHUh?=
U-266 MXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUTJR|UxRTJ6Lk[zOlYh|ryP MmDlV2FPT1KHUh?=
SNU-C1 NIi2XJNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M2TGbGlEPTB;MkiuPVQ{KM7:TR?= MkLpV2FPT1KHUh?=
SW962 NInKcWtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MonyTWM2OD1|MD6yO|Q4KM7:TR?= M{jhVXNCVkeURWK=
Raji MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWjwXoxHUUN3ME2zNE42PTl{IN88US=> MmG0V2FPT1KHUh?=
KNS-42 NHuyUGFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGDIZnpKSzVyPUOwMlg6PTZizszN Ml\0V2FPT1KHUh?=
LB996-RCC MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M{TTU2lEPTB;M{GuNVcxOiEQvF2= MXvTRW5IWkWU
CHP-126 NUHFcVdRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NEHZcYRKSzVyPUOxMlE6QDRizszN NX3MXmxtW0GQR2LFVi=>
RXF393 MoHrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVr4UlBpUUN3ME2zNk41QTdizszN NVTlRpp6W0GQR2LFVi=>
COLO-684 NWDaV3c4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXjJR|UxRTN{Lk[0N|gh|ryP MWjTRW5IWkWU
A704 MkLQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUPJR|UxRTN|LkW1N|gh|ryP M{Dt[XNCVkeURWK=
A253 M4WyWWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWnNZYJvUUN3ME2zN{42QDV{IN88US=> MkfUV2FPT1KHUh?=
KNS-81-FD NHH6eFVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Ml;RTWM2OD1|ND61OFU3KM7:TR?= MXHTRW5IWkWU
TE-441-T MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWjJeGU{UUN3ME2zOE43OzdzIN88US=> MnHpV2FPT1KHUh?=
HCC2157 MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NH2zWpFKSzVyPUO1MlQ3OTlizszN NGO5bnhUSU6JUlXS
ES3 M13Y[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MkPGTWM2OD1|Nj62O|Uh|ryP NVzCZlA2W0GQR2LFVi=>
NCI-H1155 NF3vZ4tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NE\VdohKSzVyPUO3MlgyPSEQvF2= NHzS[XVUSU6JUlXS
SNU-C2B Ml;vS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYDJR|UxRTN6LkG2OVQh|ryP NGTQe5NUSU6JUlXS
JAR MoO0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUXJR|UxRTN6LkK0OFkh|ryP NEnEOG5USU6JUlXS
GDM-1 M3XPW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1rvWWlEPTB;M{iuPVEyPiEQvF2= NXe3b5VSW0GQR2LFVi=>
KU812 NXOyRXRkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFvISIhKSzVyPUSxMlUxPyEQvF2= MoH1V2FPT1KHUh?=
BC-1 M4DWfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWXJR|UxRTR{Lk[3N|Eh|ryP NH7qUIFUSU6JUlXS
GI-1 NW\xW|ZZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MWnJR|UxRTR{LkmxPVIh|ryP MWjTRW5IWkWU
NCI-H1694 MnnoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnjkTWM2OD12ND65OFczKM7:TR?= MlfFV2FPT1KHUh?=
DG-75 M3PTS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MnjzTWM2OD12NT6xOVc4KM7:TR?= MYjTRW5IWkWU
COR-L88 Mnn1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1vKXmlEPTB;NEWuNlc4QCEQvF2= NGm4fHVUSU6JUlXS
LS-513 MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVizNodSUUN3ME20OU46OTV4IN88US=> NF;SN5NUSU6JUlXS
HD-MY-Z MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MY\JR|UxRTR4LkS2NVIh|ryP MnLJV2FPT1KHUh?=
L-363 MlvYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVyzbnNRUUN3ME20Ok45QDFizszN NH\IbZVUSU6JUlXS
TE-6 NWLzWmRzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MXTJR|UxRTR6LkS0OkDPxE1? NELwc25USU6JUlXS
NCI-H345 NUHrWW14T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXHTTnUyUUN3ME20PE41PjhizszN NHracFdUSU6JUlXS
TE-5 NVX6TodxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHn2SZVKSzVyPUS5MlcyOThizszN M{TzdXNCVkeURWK=

... 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