VX-680 (Tozasertib, MK-0457)

Catalog No.S1048

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.

Price Stock Quantity  
USD 134 In stock
USD 147 In stock
USD 370 In stock
USD 470 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

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

VX-680 (Tozasertib, MK-0457) Chemical Structure
Molecular Weight: 464.59

Validation & Quality Control

Cited by 35 publications:

15 customer reviews :

Quality Control & MSDS

Related Compound Libraries

VX-680 (Tozasertib, MK-0457) is available in the following compound libraries:

Aurora Kinase Inhibitors with Unique Features

  • Pan Aurora Kinase Inhibitors

    Danusertib (PHA-739358) Pan-Aurora kinase inhibitor, Aurora A/B/C, IC50=13 nM/79 nM/61 nM. SNS-314 Mesylate Pan-Aurora kinase inhibitor, Aurora A/B/C, IC50=9 nM/31 nM/3 nM.

  • Most Potent Aurora Kinase Inhibitor

    MK-5108 (VX-689) Aurora A, IC50=0.064 nM.

  • Aurora Kinase Inhibitor in Clinical Trial

    Alisertib (MLN8237) Phase III for Relapsed/Refractory Peripheral T-Cell Lymphoma.

  • Classic Aurora Kinase Inhibitor

    Hesperadin Potently inhibits Aurora B with IC50 of 250 nM.

Product Information

  • Compare Aurora Kinase Inhibitors
    Compare Aurora Kinase Products
  • Research Area
  • Inhibition Profile
  • VX-680 (Tozasertib, MK-0457) Mechanism

Product Description

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)
IC50 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 LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
BE-13MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NFHTeoVKSzVyPUCuNFA{OzhizszNMnHiV2FPT1KHUh?=
RS4-11MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MmHNTWM2OD1yLkCwOFA1KM7:TR?=MXzTRW5IWkWU
MFH-inoM2f1Nmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NYjkc2JEUUN3ME2wMlAxQTlizszNMUTTRW5IWkWU
NTERA-S-cl-D1NHyxd25Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MmLYTWM2OD1yLkCxOFM1KM7:TR?=MYHTRW5IWkWU
697NU\wcpZnT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NYTBTpJNUUN3ME2wMlAzPDdzIN88US=>MXHTRW5IWkWU
NALM-6MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?Ml3PTWM2OD1yLkCyOVUzKM7:TR?=MmfHV2FPT1KHUh?=
ES8MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M36xdmlEPTB;MD6wOFYyOyEQvF2=MoGwV2FPT1KHUh?=
HUTU-80M2WwOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NWnNcJdnUUN3ME2wMlA2Ojl7IN88US=>NVXPXXFoW0GQR2LFVi=>
MV-4-11NYi0WGRPT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXTZcpJTUUN3ME2wMlA4Pzh{IN88US=>M{f5[XNCVkeURWK=
MONO-MAC-6MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NET1U|VKSzVyPUCuNFc5PzlizszNNV7PPGhTW0GQR2LFVi=>
LC-2-adNFS3NY1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M3XGUGlEPTB;MD6wPFc5QSEQvF2=MVLTRW5IWkWU
BL-41NIGxVHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MUTJR|UxRTBwMUC0OFUh|ryPNFOwXG1USU6JUlXS
A4-FukNWT5WpZxT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NWrCcnhrUUN3ME2wMlEyPTZ|IN88US=>NVjQNWw1W0GQR2LFVi=>
SW954MnS0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?Mn31TWM2OD1yLkGyNlI6KM7:TR?=Mk[xV2FPT1KHUh?=
BV-173MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MmToTWM2OD1yLkGyOlQyKM7:TR?=M2Twb3NCVkeURWK=
TE-11MnXuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NI\YU2VKSzVyPUCuNVQ6QDJizszNMV7TRW5IWkWU
SK-UT-1NYXxUGVWT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NVLGWXMyUUN3ME2wMlE2QTZ3IN88US=>MlLuV2FPT1KHUh?=
SIG-M5NFzMUmZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M{K5OGlEPTB;MD6xOlcxPyEQvF2=MYfTRW5IWkWU
OCUB-MMlHZS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NWP4eJJMUUN3ME2wMlE3QTh|IN88US=>MoHCV2FPT1KHUh?=
K052NHPwc|dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NVjCWnQ3UUN3ME2wMlE6PDhizszNMVPTRW5IWkWU
VA-ES-BJNFywVVNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NEezPIJKSzVyPUCuNlAxQDZizszNNHPIVnBUSU6JUlXS
SW982MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NXv4[mpvUUN3ME2wMlIyOzhizszNNYfqZppbW0GQR2LFVi=>
LB647-SCLCNHjFc3hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MoX0TWM2OD1yLkKxOVI{KM7:TR?=MojMV2FPT1KHUh?=
PSN1NV\3V2NrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NX3N[2J1UUN3ME2wMlIzODJ4IN88US=>M2nHc3NCVkeURWK=
BB30-HNCMY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MVLJR|UxRTBwMkK1PVEh|ryPM2jtcXNCVkeURWK=
ST486MoPQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NFnlWHVKSzVyPUCuNlMxQDdizszNNVPT[lE1W0GQR2LFVi=>
MOLT-4NU\TNoVRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M3\rTmlEPTB;MD6yN|M{PyEQvF2=Mn\OV2FPT1KHUh?=
EW-16MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MV;JR|UxRTBwMkO3Olgh|ryPNIrqe|RUSU6JUlXS
KS-1NH34XZVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MoXxTWM2OD1yLkKzO|g2KM7:TR?=NIDSdYdUSU6JUlXS
SRNH2wNWJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MmDnTWM2OD1yLkK0OVY1KM7:TR?=M3KyXnNCVkeURWK=
KM12MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M3PHNGlEPTB;MD6yOlM3KM7:TR?=Mn[zV2FPT1KHUh?=
EM-2NFz5V5pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NFfzTHNKSzVyPUCuNlY3PDFizszNNVXucYtHW0GQR2LFVi=>
MEG-01MmDIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MX\JR|UxRTBwMke4OFkh|ryPMUfTRW5IWkWU
NB13NEXScIlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M{jlOGlEPTB;MD6yO|k5PCEQvF2=MkLHV2FPT1KHUh?=
RKONXLy[IFmT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NV7MUWhZUUN3ME2wMlMxQDF|IN88US=>M2L5TnNCVkeURWK=
CESSNV7KW2ZlT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NVXOUFJmUUN3ME2wMlMyOzJ6IN88US=>MUDTRW5IWkWU
EoL-1-cellM{\HdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NF;YdmZKSzVyPUCuN|M1PTlizszNMm\VV2FPT1KHUh?=
DOHH-2MkDPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M1HHOmlEPTB;MD6zN|c5OSEQvF2=NGjC[FJUSU6JUlXS
A388NWXhflVpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NF7EcFVKSzVyPUCuN|QxQDZizszNM4\pR3NCVkeURWK=
LAMA-84NIH2bJNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NGXVZ4FKSzVyPUCuN|UyPzhizszNMYDTRW5IWkWU
IMR-5MV3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NXvY[WZvUUN3ME2wMlM2PTRizszNM33hWHNCVkeURWK=
KARPAS-422NYjRfm4{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MWPJR|UxRTBwM{eyO|Ih|ryPMnHvV2FPT1KHUh?=
MRK-nu-1M{HnRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MWrJR|UxRTBwM{ixN{DPxE1?MV7TRW5IWkWU
BL-70NIm5do9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NFHtbmtKSzVyPUCuN|g6PzRizszNMVHTRW5IWkWU
LXF-289Mmn6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M2LoRWlEPTB;MD60NFQxPiEQvF2=NV;HT|lXW0GQR2LFVi=>
RL95-2NEXQVIFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NIrsWm5KSzVyPUCuOFA2PjdizszNNIKxVGJUSU6JUlXS
QIMR-WILM1;Jcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MWjJR|UxRTBwNEK2O|Yh|ryPMmLtV2FPT1KHUh?=
K-562M2TrSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NYPicIpiUUN3ME2wMlQ{PDd{IN88US=>Mn3zV2FPT1KHUh?=
NCI-H510ANYXKOFRCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M2\Be2lEPTB;MD60N|gzOyEQvF2=M3fZfHNCVkeURWK=
NCI-H524MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MV7JR|UxRTBwNUGxOFch|ryPMXrTRW5IWkWU
KE-37M2PDbWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NU[1Ung4UUN3ME2wMlUzOTB{IN88US=>NXfZPVE4W0GQR2LFVi=>
KP-N-YSNHTtSYZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NIDsSHFKSzVyPUCuOVQ{QTJizszNMVvTRW5IWkWU
LS-411NMXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NITaPW9KSzVyPUCuOVc4PTJizszNNXPu[FkzW0GQR2LFVi=>
CTV-1M{\F[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NVLpRZF2UUN3ME2wMlU5Pzd|IN88US=>NYHDemFzW0GQR2LFVi=>
NCI-SNU-16MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MYHJR|UxRTBwNkO1O|Eh|ryPMWrTRW5IWkWU
HT-144M1y1[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NE\PbplKSzVyPUCuOlM4QThizszNMkjDV2FPT1KHUh?=
NCI-H187NIC4fpFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M1v4T2lEPTB;MD62OFE{KM7:TR?=NHLRepRUSU6JUlXS
OCI-AML2M1HIfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MmfUTWM2OD1yLk[0OFA{KM7:TR?=NEHKdlVUSU6JUlXS
CCRF-CEMMX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MUjJR|UxRTBwNkWzOFYh|ryPNXraRmFsW0GQR2LFVi=>
ONS-76NH32N3pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MXnJR|UxRTBwNk[0OVgh|ryPMVHTRW5IWkWU
IST-SL2MmrGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M{jQXGlEPTB;MD63NVk5OiEQvF2=NGHNWG9USU6JUlXS
NB6MmHtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M4rZNWlEPTB;MD63O|I2PCEQvF2=NWLvRphRW0GQR2LFVi=>
SK-PN-DWNUHQbWdOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NYjaeZVFUUN3ME2wMlc6OTRizszNM2\QOXNCVkeURWK=
HCC1599M3HUd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7Mnr4TWM2OD1yLkiwPFc1KM7:TR?=NF\uTHJUSU6JUlXS
MC116NHy1[2tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NGnqO3RKSzVyPUCuPFUxOTFizszNNY\LXVU{W0GQR2LFVi=>
TE-15MmHBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MYfJR|UxRTBwOEWwPVgh|ryPM2HXeXNCVkeURWK=
HOP-62MmnHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NEH5c2lKSzVyPUCuPFY{OjlizszNMlLyV2FPT1KHUh?=
TGBC24TKBNEHkRXZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M3:1WGlEPTB;MD64OlM5PSEQvF2=NXvHcVJXW0GQR2LFVi=>
HCE-4NIH4Tm9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M2G0OWlEPTB;MD64PFA3OyEQvF2=Mk\CV2FPT1KHUh?=
ALL-POM4XvVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7Ml\WTWM2OD1yLki4NVc2KM7:TR?=NE[4VXhUSU6JUlXS
KGNNWDqd2hXT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MXLJR|UxRTBwOEm5PVUh|ryPMVTTRW5IWkWU
ML-2MoLvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M4P0ZWlEPTB;MD65NFI2QSEQvF2=NX\WV2d[W0GQR2LFVi=>
ES4NVTa[nY2T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NGnDOIVKSzVyPUCuPVEyOjhizszNMX\TRW5IWkWU
SF126NUjLO21YT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXTuUmRVUUN3ME2wMlk1QDF7IN88US=>M3;HRnNCVkeURWK=
SK-N-DZMoPrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MkjDTWM2OD1yLkm2NVg6KM7:TR?=MUTTRW5IWkWU
HCC1187MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MYHJR|UxRTFwMEC1NFUh|ryPMkLZV2FPT1KHUh?=
DU-4475NUXtdnpJT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=Mn3BTWM2OD1zLkCxO|U3KM7:TR?=NUTYdpJuW0GQR2LFVi=>
NKM-1NHXl[5BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NYXrfnB1UUN3ME2xMlAzPzd3IN88US=>M4rSdnNCVkeURWK=
HL-60MmOwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MmK3TWM2OD1zLkC2OVc1KM7:TR?=NEmwNGhUSU6JUlXS
SBC-1NVX4fm02T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NYnLSYxiUUN3ME2xMlEzPTR{IN88US=>NGP4Wo1USU6JUlXS
TE-10NWPM[3BKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NV7IU3RkUUN3ME2xMlEzQTR4IN88US=>NH;MbGdUSU6JUlXS
ETK-1M2\0NGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NITBe|BKSzVyPUGuNVM3OTNizszNNGf0Z2pUSU6JUlXS
HAL-01MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MmHaTWM2OD1zLkG2O|A6KM7:TR?=MmLkV2FPT1KHUh?=
BB65-RCCNXrIU5o5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MkHvTWM2OD1zLkG4NFA2KM7:TR?=MmLLV2FPT1KHUh?=
EW-1M1LLe2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MnPETWM2OD1zLkG4OVYzKM7:TR?=MnHTV2FPT1KHUh?=
SK-NEP-1M4LvWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MYHJR|UxRTFwMkGxNVEh|ryPMVnTRW5IWkWU
SK-LMS-1NEDSSpJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M3LwZWlEPTB;MT6yNlIyOiEQvF2=NYXrcIRHW0GQR2LFVi=>
DELM163O2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NVjMVWVYUUN3ME2xMlI2PjR|IN88US=>M1fobnNCVkeURWK=
GT3TKBM1\mPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NYXSbm1DUUN3ME2xMlI5ODV5IN88US=>MVPTRW5IWkWU
MOLT-16MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NG\LTplKSzVyPUGuN|U1ODVizszNMkTxV2FPT1KHUh?=
CMKM{LLeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NHvCeFJKSzVyPUGuOFIyOTdizszNMYHTRW5IWkWU
NB5MofIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MmqwTWM2OD1zLk[0NlI6KM7:TR?=NIKwUJhUSU6JUlXS
NCI-H1963NXnRVJlKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M2fVS2lEPTB;MT63NFU5OyEQvF2=MXfTRW5IWkWU
KURAMOCHIMnvWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NHHiTmVKSzVyPUGuO|g6OTFizszNMmHqV2FPT1KHUh?=
TE-8NEPuU2hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M{nPemlEPTB;MT64NFM3QCEQvF2=MmnTV2FPT1KHUh?=
NCI-H1304M17Jc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NEnxdXZKSzVyPUGuPFMxPzNizszNM4fudnNCVkeURWK=
A101DMV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NUDPTmN1UUN3ME2xMlg4Ozl3IN88US=>M3Ljc3NCVkeURWK=
SCLC-21HNUe1N3A{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NWfHTGdoUUN3ME2xMlk4ODV5IN88US=>MlPBV2FPT1KHUh?=
GB-1NWDyO3ByT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MWfJR|UxRTJwMEG2OFch|ryPNFXVZpVUSU6JUlXS
KARPAS-45MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MVfJR|UxRTJwMEK2OVQh|ryPM1rJeXNCVkeURWK=
ATN-1M3TXOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7M{Dx[mlEPTB;Mj6wNlg2QCEQvF2=NGfRNW5USU6JUlXS
NCI-H720NXXFZldkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M{K1OWlEPTB;Mj6wOlI1PCEQvF2=NV2xc2V[W0GQR2LFVi=>
RPMI-6666Mn7LS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MXfJR|UxRTJwMU[yNFch|ryPMULTRW5IWkWU
NB17NHrNTJZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M2fPZ2lEPTB;Mj6yPVI4KM7:TR?=MlLQV2FPT1KHUh?=
IST-SL1NXrxUGdET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NUXNbIZCUUN3ME2yMlI6PzZ3IN88US=>M2SxVXNCVkeURWK=
SH-4MkS3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NYjoeIo5UUN3ME2yMlMzPDZ7IN88US=>MorjV2FPT1KHUh?=
K5NGjpbZlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M3Hr[mlEPTB;Mj60NFMyQSEQvF2=NV\FSHB[W0GQR2LFVi=>
OVCAR-4MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MYrJR|UxRTJwNE[xN{DPxE1?M4rPfXNCVkeURWK=
ACNM3n6cGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NV\ubmtCUUN3ME2yMlUxOjF|IN88US=>Mom4V2FPT1KHUh?=
TGWNFq4TnlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NUezW41{UUN3ME2yMlY2QDN{IN88US=>NUK3e2djW0GQR2LFVi=>
NCI-H2107MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M3vHT2lEPTB;Mj64N|cyOSEQvF2=Mo\1V2FPT1KHUh?=
NCI-H82MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NFPTS5ZKSzVyPUKuPFM5OzhizszNM1HVVnNCVkeURWK=
SK-N-FIMn3tS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M1noOmlEPTB;Mj64Olg3QCEQvF2=NVfZ[Vc4W0GQR2LFVi=>
LB1047-RCCNGHz[XJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MoXiTWM2OD1{Lki4NVI3KM7:TR?=NVmwRXRXW0GQR2LFVi=>
LU-134-AMX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MWXJR|UxRTJwOEmyOkDPxE1?MnHhV2FPT1KHUh?=
NCI-H209NHz4Z5lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MmHtTWM2OD1{LkmxNlU{KM7:TR?=NFjBTJNUSU6JUlXS
NOMO-1NXnC[2RIT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXT2eYpWUUN3ME2zMlAzOjd2IN88US=>NXfBXnNkW0GQR2LFVi=>
RH-1MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NXfENVBZUUN3ME2zMlE4OjlzIN88US=>NV[1U|BiW0GQR2LFVi=>
LOUCYNXPpV2ZyT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MXHJR|UxRTNwMUi2PVMh|ryPNFP4eIVUSU6JUlXS
TE-9Ml3VS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MWDJR|UxRTNwMk[3N|Yh|ryPMV3TRW5IWkWU
PF-382MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NIXF[ZpKSzVyPUOuN|U4PzhizszNMV;TRW5IWkWU
RPMI-8402MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MoWyTWM2OD1|LkW4OlA{KM7:TR?=MYfTRW5IWkWU
HELMXfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M4rIXGlEPTB;Mz62N|Ih|ryPM4\EWnNCVkeURWK=
NOS-1NVvlWW5DT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MnTPTWM2OD1|Lki0O|U1KM7:TR?=MmDEV2FPT1KHUh?=
ES1MlHzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NXq5O2sxUUN3ME2zMlkzOjl|IN88US=>M{\UNXNCVkeURWK=
NCI-H2171NI\tXpdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=Moj6TWM2OD1|LkmyOFI{KM7:TR?=M{HVNXNCVkeURWK=
NCI-H747M{PxT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NVThTYd[UUN3ME2zMlk1OjJzIN88US=>MXPTRW5IWkWU
MHH-NB-11NWrRUINsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=Ml7jTWM2OD1|Lkm1N|EzKM7:TR?=MUXTRW5IWkWU
MZ1-PCMmToS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M2nEfWlEPTB;Mz65PVI1KM7:TR?=MVnTRW5IWkWU
MMAC-SFMWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NXzYUnRkUUN3ME20MlAzPDZ5IN88US=>M4fh[XNCVkeURWK=
NMC-G1MXvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MlrWTWM2OD12LkKyO|I{KM7:TR?=Mn;mV2FPT1KHUh?=
SW872MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MWTJR|UxRTRwM{SzOEDPxE1?NEfGbXRUSU6JUlXS
TE-12NWLxW45oT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NX\QZpl4UUN3ME20MlU3Ozl2IN88US=>NUSxSZhHW0GQR2LFVi=>
LU-139NIDhRotIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NHPrSYxKSzVyPUSuOlE5OzVizszNNVXPUlJYW0GQR2LFVi=>
HC-1NYPRUHhFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NUPaOJBPUUN3ME20MlY6PDl2IN88US=>NUC2NnRJW0GQR2LFVi=>
COR-L279Mlf2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MnTJTWM2OD12Lke1PFkyKM7:TR?=Mo[zV2FPT1KHUh?=
SF268MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NYDvSGJoUUN3ME20Mlc6QTF4IN88US=>MV;TRW5IWkWU
MC-CARNYrESmlOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NWj5Vo1mUUN3ME21MlA3PzV5IN88US=>NXTxdlVQW0GQR2LFVi=>
TK10M4\W[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MlO5TWM2OD13LkO1OFY6KM7:TR?=NGT2c3VUSU6JUlXS
TE-1MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NFvWcmtKSzVyPUWuOFkxODRizszNNX34NXd3W0GQR2LFVi=>
NCI-H2126NVv6R3dUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NUHo[pE2UUN3ME21MlY1PTd2IN88US=>NVTjblc6W0GQR2LFVi=>
DaudiM4Gyd2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7MXzJR|UxRTVwNkmxNkDPxE1?NF\ue25USU6JUlXS
NCI-H1648M{TQPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NYTqfmpkUUN3ME21MlgyPDV2IN88US=>MYjTRW5IWkWU
OS-RC-2MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M3fZfmlEPTB;NT65PFU6PyEQvF2=M4rXV3NCVkeURWK=
DJM-1NFv6RVdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NXqxXIk2UUN3ME22MlM1PjZ4IN88US=>M3:1RnNCVkeURWK=
LS-1034MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NYTrVVNvUUN3ME22Mlc2PjZizszNNIri[|JUSU6JUlXS
NCI-H1581NUDm[|I5T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M4POTmlEPTB;Nj63PFQxPSEQvF2=MoDDV2FPT1KHUh?=
UACC-257MlyzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M{XHeGlEPTB;Nz6wOFUyOiEQvF2=Mnz0V2FPT1KHUh?=
KM-H2M1O4eGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MXXJR|UxRTdwMUi0OVch|ryPNHnmNJNUSU6JUlXS
NCI-H1436NHe5RpNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NHT6SWtKSzVyPUeuOlk6OzJizszNNF3mTFBUSU6JUlXS
IA-LMNW\FSWROT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MWHJR|UxRTdwOEW5JO69VQ>?MVzTRW5IWkWU
NCI-H526NXLnVYZGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NGHaeZNKSzVyPUiuNlU3OzdizszNMWfTRW5IWkWU
GCIYNV35WnhUT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NX[1To5PUUN3ME24MlM3QTZ3IN88US=>MlznV2FPT1KHUh?=
CP67-MELMoG2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NGrxbGxKSzVyPUiuOVMzPiEQvF2=NV\HZndKW0GQR2LFVi=>
KALS-1NFi2OlJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M{HlbWlEPTB;OD64N|g2OSEQvF2=Mn71V2FPT1KHUh?=
NCI-H1770MlO1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M4DOW2lEPTB;OD65NFI3PSEQvF2=MUfTRW5IWkWU
8-MG-BAMUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?Mn\iTWM2OD17LkOyPFQ1KM7:TR?=NWPQS5NzW0GQR2LFVi=>
KY821M1TyV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NUXmXFNRUUN3ME25Mlc4PDh2IN88US=>NV60SHo5W0GQR2LFVi=>
SNB75NEHNPFBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M3Xs[GlEPTB;MUCuNFc3KM7:TR?=NWr0S4xTW0GQR2LFVi=>
NCCITNHnTWFhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NEHHVYdKSzVyPUGxMlA2QDJizszNMYnTRW5IWkWU
SJSA-1MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MYfJR|UxRTFzLkK4PVEh|ryPMYnTRW5IWkWU
LB373-MEL-DNFP2PYdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M{jqdmlEPTB;MUGuN|gzPyEQvF2=NWDaR3FtW0GQR2LFVi=>
TALL-1MYDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NWexO4UxUUN3ME2xNU41ODV6IN88US=>NUHBblJEW0GQR2LFVi=>
NB69NWrIcoVFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NGO5TGtKSzVyPUGxMlc4ODVizszNMWDTRW5IWkWU
NCI-H1355MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MlmwTWM2OD1zMT65OFI3KM7:TR?=M4SzSHNCVkeURWK=
DMS-153NYDveXFsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MYTJR|UxRTF{LkC0NlYh|ryPNIi0R4VUSU6JUlXS
OPM-2Ml;jS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M2DSRWlEPTB;MUKuNVU6PiEQvF2=M{HSfnNCVkeURWK=
NB1NYnYSVFMT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M2HTTmlEPTB;MUKuNlkh|ryPMXPTRW5IWkWU
A3-KAWNUfDNWZVT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NFPJOo5KSzVyPUGyMlMzOzZizszNNYjyRot1W0GQR2LFVi=>
NCI-H1882NX\i[IdoT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXjFT|ZvUUN3ME2xNk41ODZ4IN88US=>MoDrV2FPT1KHUh?=
KG-1M3vnR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NV\lZ5dYUUN3ME2xNk43PTR3IN88US=>M2f1NnNCVkeURWK=
LC4-1MmLFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NELqVXRKSzVyPUGyMlc4ODZizszNMmfiV2FPT1KHUh?=
HCE-TMkf5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NGew[lVKSzVyPUGzMlAxPDlizszNNITxWYRUSU6JUlXS
NEC8MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NV;0b3NEUUN3ME2xN{4yODN6IN88US=>M2G4TXNCVkeURWK=
IST-MEL1Mn;4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NXm4WFU{UUN3ME2xN{42Pzh6IN88US=>MVHTRW5IWkWU
EW-3MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MmLiTWM2OD1zMz63OFAzKM7:TR?=MXrTRW5IWkWU
CTB-1NHv6[Y1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=Mk\lTWM2OD1zND6wN|I6KM7:TR?=M1f3bnNCVkeURWK=
LS-123MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?Mn;6TWM2OD1zND6xOVg5KM7:TR?=NVjjZWdNW0GQR2LFVi=>
NCI-H1417MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?Mme4TWM2OD1zND6zNFUzKM7:TR?=M1vocHNCVkeURWK=
MZ7-melNF;rNnFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MkTUTWM2OD1zND60OFM{KM7:TR?=NHzzVJZUSU6JUlXS
JiyoyeP-2003NGDkNHVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NX\iWJpFUUN3ME2xOU43OzJ4IN88US=>NX36c3VRW0GQR2LFVi=>
ES6NWLYcG9ST3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M37EZ2lEPTB;MU[uNlM3OSEQvF2=NX3PNndSW0GQR2LFVi=>
HHMlLXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MmjtTWM2OD1zNz6xPVY{KM7:TR?=M161ZnNCVkeURWK=
SF539NHPLV45Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NYPP[VFTUUN3ME2xO{46QTJ{IN88US=>MWDTRW5IWkWU
Calu-6NGG3dWxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MYHJR|UxRTF7LkKzPUDPxE1?NVm1ZoRRW0GQR2LFVi=>
SK-MM-2MnvJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MU\JR|UxRTF7LkW1OUDPxE1?NIjiOWtUSU6JUlXS
IST-MES1MU\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NYW1S4FGUUN3ME2xPU43PjZ|IN88US=>NF\TUFlUSU6JUlXS
GI-ME-NMl24S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NFOz[ZBKSzVyPUG5MlgzOjdizszNNX34UXNMW0GQR2LFVi=>
CAL-148M1zGNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NGnXU2ZKSzVyPUKwMlk6OzRizszNMYnTRW5IWkWU
EVSA-TNUHsWoRET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NYX5c3BoUUN3ME2yNU4yPDl7IN88US=>MmPzV2FPT1KHUh?=
LP-1M4LWWmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7Ml7aTWM2OD1{MT6zOFMzKM7:TR?=MkPCV2FPT1KHUh?=
BOKUMnjjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MkTXTWM2OD1{MT60OVM{KM7:TR?=NHfPUpVUSU6JUlXS
KLEMoD1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MV7JR|UxRTJ{LkG5NFMh|ryPMmXsV2FPT1KHUh?=
LB831-BLCNHj2cI5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MmDWTWM2OD1{NT6xOVI3KM7:TR?=MUfTRW5IWkWU
NCI-H889NULWfmtKT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MljhTWM2OD1{NT6xPVMyKM7:TR?=NHPV[mVUSU6JUlXS
REHMVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MY\JR|UxRTJ3LkS2O|Eh|ryPNGD4UHhUSU6JUlXS
KP-N-RT-BM-1M4DWbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NEj2Um1KSzVyPUK1MlQ4PTJizszNM{TtN3NCVkeURWK=
MPP-89NGTKOo5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M1qzNmlEPTB;MkWuOVMyPCEQvF2=NXT3epE6W0GQR2LFVi=>
no-11MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NV7rdoF3UUN3ME2yOU44PDdizszNM3G5UXNCVkeURWK=
NCI-H748NIDWS|NIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M4HLSWlEPTB;MkWuO|YzPyEQvF2=MY\TRW5IWkWU
LB2518-MELM4fMRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NFrPbIxKSzVyPUK3MlE4PzNizszNMXLTRW5IWkWU
TGBC1TKBNGHWPFFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MUXJR|UxRTJ5LkW1PFUh|ryPNUD0NVkzW0GQR2LFVi=>
MHH-PREB-1NF\kTWRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MXTJR|UxRTJ6LkC3N|Qh|ryPNYHuN4VvW0GQR2LFVi=>
MZ2-MELMmLKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M1Xa[GlEPTB;MkiuOlE1OyEQvF2=MWPTRW5IWkWU
U-266NYjodJR1T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=MVHJR|UxRTJ6Lk[zOlYh|ryPMnnmV2FPT1KHUh?=
SNU-C1NVTUeVk6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=NXjqZos5UUN3ME2yPE46PDNizszNMUPTRW5IWkWU
SW962MUnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NH;D[HlKSzVyPUOwMlI4PDdizszNMXLTRW5IWkWU
RajiMWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MX\JR|UxRTNyLkW1PVIh|ryPMUPTRW5IWkWU
KNS-42MmLCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NIXJdHhKSzVyPUOwMlg6PTZizszNMlP4V2FPT1KHUh?=
LB996-RCCNUXKSnJDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=M13J[mlEPTB;M{GuNVcxOiEQvF2=MoDMV2FPT1KHUh?=
CHP-126M{nveWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MlLQTWM2OD1|MT6xPVg1KM7:TR?=M4P2THNCVkeURWK=
RXF393M{DJ[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MoLUTWM2OD1|Mj60PVch|ryPMUjTRW5IWkWU
COLO-684MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?Mn70TWM2OD1|Mj62OFM5KM7:TR?=NEHrZ4VUSU6JUlXS
A704MnrES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NGXSXWpKSzVyPUOzMlU2OzhizszNNYX3bohFW0GQR2LFVi=>
A253MnHLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MnPjTWM2OD1|Mz61PFUzKM7:TR?=MV\TRW5IWkWU
KNS-81-FDNF7jd3ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=MlfzTWM2OD1|ND61OFU3KM7:TR?=Mmj0V2FPT1KHUh?=
TE-441-TNI\ZPWxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=NXLifoo3UUN3ME2zOE43OzdzIN88US=>MkPzV2FPT1KHUh?=
HCC2157M372TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NWXCZpc{UUN3ME2zOU41PjF7IN88US=>NFLQRVNUSU6JUlXS
ES3MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?NVzhWmkzUUN3ME2zOk43PzVizszNNF71[pJUSU6JUlXS
NCI-H1155MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MX;JR|UxRTN5LkixOUDPxE1?NEnVfI1USU6JUlXS
SNU-C2BMVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M3SzS2lEPTB;M{iuNVY2PCEQvF2=NHviT5pUSU6JUlXS
JARMXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MU\JR|UxRTN6LkK0OFkh|ryPMmn0V2FPT1KHUh?=
GDM-1M{OydWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NUjYPWNUUUN3ME2zPE46OTF4IN88US=>MlPBV2FPT1KHUh?=
KU812NFP2e|lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=Mn3uTWM2OD12MT61NFch|ryPMnfaV2FPT1KHUh?=
BC-1M4C3OWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MXTJR|UxRTR{Lk[3N|Eh|ryPNVvu[oFDW0GQR2LFVi=>
GI-1MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?M{fxNGlEPTB;NEKuPVE6OiEQvF2=MVnTRW5IWkWU
NCI-H1694MoS5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?MUfJR|UxRTR2Lkm0O|Ih|ryPM1\1NHNCVkeURWK=
DG-75NIizR2VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=M1rEXWlEPTB;NEWuNVU4PyEQvF2=NXHucXhQW0GQR2LFVi=>
COR-L88M37XeWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7MV\JR|UxRTR3LkK3O|gh|ryPNH3MOGJUSU6JUlXS
LS-513M1nQW2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7NV;IWVI6UUN3ME20OU46OTV4IN88US=>M1XvTnNCVkeURWK=
HD-MY-ZMkPjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?M2G0OmlEPTB;NE[uOFYyOiEQvF2=NIr1Z4xUSU6JUlXS
L-363MnvES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?NGfmNZlKSzVyPUS2Mlg5OSEQvF2=NV7Q[JZwW0GQR2LFVi=>
TE-6MVLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?MXzJR|UxRTR6LkS0OkDPxE1?NFPXO3ZUSU6JUlXS
NCI-H345M3G2bGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7NIrIZ3hKSzVyPUS4MlQ3QCEQvF2=NWDafIZmW0GQR2LFVi=>
TE-5NYDnZlJET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm=Mn3WTWM2OD12OT63NVE5KM7:TR?=NEXl[FJUSU6JUlXS

... 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]
Features

Protocol(Only for Reference)

Kinase Assay:

[3]

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 Assay:

[2]

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.

Animal Study:

[1]

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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Harrington EA, et al. Nat Med. 2004, 10(3), 262-267.

[2] Arlot-Bonnemains Y, et al. Endocr Relat Cancer. 2008, 15(2), 559-568.

view more

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-30)

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

view more

Chemical Information

Download VX-680 (Tozasertib, MK-0457) SDF
Molecular Weight (MW) 464.59
Formula

C23H28N8OS

CAS No. 639089-54-6
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 93 mg/mL (200.17 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
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 Name N-(4-(4-(5-methyl-1H-pyrazol-3-ylamino)-6-(4-methylpiperazin-1-yl)pyrimidin-2-ylthio)phenyl)cyclopropanecarboxamide

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.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related Aurora Kinase Products

  • Ro-3306

    RO-3306 is an ATP-competitive, and selective CDK1 inhibitor with Ki of 20 nM, >15-fold selectivity against a diverse panel of human kinases.

  • CCG-1423

    CCG-1423 is a specific RhoA pathway inhibitor, which inhibits SRF-mediated transcription.

  • ML141

    ML141 is a potent, selective and reversible non-competitive inhibitor of Rho family GTPase cdc42 with IC50 of 200 nM.

  • Alisertib (MLN8237)

    Alisertib (MLN8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM in a cell-free assay. It has >200-fold higher selectivity for Aurora A than Aurora B. Phase 3.

    Features:First orally available inhibitor of Aurora A.

  • Barasertib (AZD1152-HQPA)

    Barasertib (AZD1152-HQPA) is a highly selective Aurora B inhibitor with IC50 of 0.37 nM in a cell-free assay, ~3700 fold more selective for Aurora B over Aurora A. Phase 1.

  • Danusertib (PHA-739358)

    Danusertib (PHA-739358) is an Aurora kinase inhibitor for Aurora A/B/C with IC50 of 13 nM/79 nM/61 nM in cell-free assays, modestly potent to Abl, TrkA, c-RET and FGFR1, and less potent to Lck, VEGFR2/3, c-Kit, CDK2, etc. Phase 2.

  • ZM 447439

    ZM 447439 is a selective and ATP-competitive inhibitor for Aurora A and Aurora B with IC50 of 110 nM and 130 nM, respectively. It is more than 8-fold selective for Aurora A/B than MEK1, Src, Lck and has little effect against CDK1/2/4, Plk1, Chk1, etc.

    Features:An Aurora selective ATP-competitive inhibitor.

  • MLN8054

    MLN8054 is a potent and selective inhibitor of Aurora A with IC50 of 4 nM in Sf9 insect cell. It is more than 40-fold selective for Aurora A than Aurora B. Phase 1.

  • MK-5108 (VX-689)

    MK-5108 (VX-689) is a highly selective Aurora A inhibitor with IC50 of 0.064 nM in a cell-free assay and is 220- and 190-fold more selective for Aurora A than Aurora B/C, while it inhibits TrkA with less than 100-fold selectivity. Phase 1.

  • Aurora A Inhibitor I

    Aurora A Inhibitor I is a novel, potent, and selective inhibitor of Aurora A with IC50 of 3.4 nM in a cell-free assay. It is 1000-fold more selective for Aurora A than Aurora B.

    Features:Aurora A Inhibitor I is a novel, potent, and selective inhibitor to Aurora A.

Recently Viewed Items

Tags: buy VX-680 (Tozasertib, MK-0457) | VX-680 (Tozasertib, MK-0457) supplier | purchase VX-680 (Tozasertib, MK-0457) | VX-680 (Tozasertib, MK-0457) cost | VX-680 (Tozasertib, MK-0457) manufacturer | order VX-680 (Tozasertib, MK-0457) | VX-680 (Tozasertib, MK-0457) distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Contact Us