Tozasertib (VX-680, MK-0457)

Name: Tozasertib (VX-680, MK-0457)
Brand: Selleck Chemicals
SKU: S1048
Rating: 5 (110 reviews)

For research use only.

Catalog No.S1048

110 publications

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

CAS No. 639089-54-6

Tozasertib (VX-680, MK-0457) is a pan-Aurora inhibitor, mostly against Aurora A with K_i_app 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. The only exceptions are Fms-related tyrosine kinase-3 (FLT-3) and BCR-ABL tyrosine kinase, which are inhibited by the Tozasertib with both Ki of 30 nM. Tozasertib induces apoptosis and autophagy. Phase 2.

Selleck's Tozasertib (VX-680, MK-0457) has been cited by 110 publications

Science, 2021, 371(6535)eabc5386

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Cancer Cell, 2014, 26(3):414-427

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Cell Stem Cell, 2012, 11(2):179-94

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Cell, 2010, 6;142(3):444-55.

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J Cell Biol, 2021, 220(2)e202008029

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Cell Rep, 2021, 36(2):109343

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PLoS Biol, 2021, 19(1):e3001029

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Cancer Lett, 2021, 521:268-280

PubMed: 34481935 ( click the link to review the publication )

Sci Rep, 2021, 11(1):17029

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Cancer Commun (Lond), 2021, 10.1002/cac2.12190

PubMed: 34251762 ( click the link to review the publication )

Breast Cancer, 2021, 10.1007/s12282-021-01242-z

PubMed: 33813687 ( click the link to review the publication )

STAR Protoc, 2021, 2(3):100495

PubMed: 34195669 ( click the link to review the publication )

J Clin Invest, 2020, 139080

PubMed: 33016928 ( click the link to review the publication )

EMBO Rep, 2020, 3;21(4):e49700

PubMed: 32030856 ( click the link to review the publication )

Cancer Res, 2020, 80(18):3841-3854

PubMed: 32690724 ( click the link to review the publication )

Cancers (Basel), 2020, 12(11)E3172

PubMed: 33126775 ( click the link to review the publication )

Cancers (Basel), 2020, 12(9)E2697

PubMed: 32967224 ( click the link to review the publication )

Mol Cancer Ther, 2020, 10.1158/1535-7163.MCT-19-1017

PubMed: 32847978 ( click the link to review the publication )

Mol Cancer Ther, 2020, 19(4):1008-1017

PubMed: 31848297 ( click the link to review the publication )

Sci Adv, 2020, 6(29):eaba1941

PubMed: 32832623 ( click the link to review the publication )

Toxicol Sci, 2020, kfaa103

PubMed: 32617558 ( click the link to review the publication )

Cancer Res, 2019, 79(1):209-219

PubMed: 30389701 ( click the link to review the publication )

Cell Death Differ, 2019, 26(3):548-564

PubMed: 30050055 ( click the link to review the publication )
Cancers (Basel), 2019, 11(10)

PubMed: 31652588 ( click the link to review the publication )

Cell Death Dis, 2019, 10(6):385

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Cell Death Dis, 2019, 10(6):432

PubMed: 31160567 ( click the link to review the publication )

Cell Chem Biol, 2019, 26(3):390-399.e5

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FEBS J, 2019, 286(5):963-974

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Antiviral Res, 2019, 170:104572

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Toxicol Sci, 2019, 10.1093/toxsci/kfz123

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Sci Rep, 2019, 9(1):1897

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Analyst, 2019, 145(1):97-106

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J Pharm Biomed Anal, 2019, doi: 101016/jjpba2019112962

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Environ Mol Mutagen, 2019, 60(6):513-533

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J Pediatr Hematol Oncol, 2019, 41(6):e359-e370

PubMed: 30702467 ( click the link to review the publication )

Int J Mol Sci, 2018, 19(12)

PubMed: 30544932 ( click the link to review the publication )

Cell Signal, 2018, 52:137-146

PubMed: 30223016 ( click the link to review the publication )

SLAS Discov, 2018, 23(2):132-143

PubMed: 28957641 ( click the link to review the publication )

Anticancer Drugs, 2018, 29(10):1004-1010

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Oncotarget, 2018,

PubMed: 29560108 ( click the link to review the publication )

Neuron, 2017, 94(6):1142-1154

PubMed: 28641113 ( click the link to review the publication )

Nat Commun, 2017, 1;8(1):1232

PubMed: 29089541 ( click the link to review the publication )

Cancer Res, 2017, 77(2):494-508

PubMed: 28069801 ( click the link to review the publication )

Oncogene, 2017, 36(44):6177-6189

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Oncogenesis, 2017, 6(2):e298

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Toxicol Sci, 2017, 162(1):146-166

PubMed: 29106658 ( click the link to review the publication )

J Biol Chem, 2017, 292(36):15028-15038

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Cell Signal, 2017, 39:74-83

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PPAR Res, 2017, 2017:4313561

PubMed: 29056962 ( click the link to review the publication )

Nat Chem Biol, 2016, 10.1038/nchembio.2017

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Nat Commun, 2016, 7:10180

PubMed: 26782714 ( click the link to review the publication )

EMBO J, 2016, 35(8):803-19

PubMed: 26929011 ( click the link to review the publication )

Proc Natl Acad Sci U S A, 2016, 113(50):14366-14371

PubMed: 28182563 ( click the link to review the publication )

Elife, 2016, 5:e11402

PubMed: 26878753 ( click the link to review the publication )

Arch Toxicol, 2016, 291(10):4939-54

PubMed: 26404763 ( click the link to review the publication )

J Biol Chem, 2016, 10.1074/jbc.M116.722751

PubMed: 27226586 ( click the link to review the publication )

Cancer Biol Ther, 2016, 17(5):566-76

PubMed: 27082306 ( click the link to review the publication )

Exp Cell Res, 2016, 344(2):153-66

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Cell Cycle, 2016, 15(15):2009-18

PubMed: 27249336 ( click the link to review the publication )

Oncol Rep, 2016, 36(2):819-26

PubMed: 27373675 ( click the link to review the publication )

Biochem Biophys Res Commun, 2016, 473(1):212-8

PubMed: 27003257 ( click the link to review the publication )

Exp Hematol, 2016, 44(3):189-93

PubMed: 26706195 ( click the link to review the publication )

Tumour Biol, 2016, 37(11):14745-14755

PubMed: 27629142 ( click the link to review the publication )

Oncotarget, 2016, 7(18):26580-92

PubMed: 27058891 ( click the link to review the publication )

Nat Cell Biol, 2015, 17(1):31-43

PubMed: 25503564 ( click the link to review the publication )

Nat Commun, 2015, 6:7935

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Clin Cancer Res, 2015, 21(23):5338-48

PubMed: 26152738 ( click the link to review the publication )

Dev Cell, 2015, 33(6):703-16

PubMed: 26051540 ( click the link to review the publication )

Dev Cell, 2015, 33(5):522-34

PubMed: 26004507 ( click the link to review the publication )

Proc Natl Acad Sci U S A, 2015, 112(19):5875-82

PubMed: 25883264 ( click the link to review the publication )

Mol Cancer Ther, 2015, 14(2):419-28

PubMed: 25522764 ( click the link to review the publication )
Oncol Rep, 2015, 34(2):803-10

PubMed: 26044736 ( click the link to review the publication )

PLoS One, 2015, 10(7):e0134306

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BMC Res Notes, 2015, 8:484

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Mol Cancer Ther, 2015, 14(6):1354-64

PubMed: 25873592 ( click the link to review the publication )

J Mol Cell Biol, 2014, 6(3):240-54

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Biochim Biophys Acta, 2014, 1843(5):934-44

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Hum Gene Ther, 2014, 25(7):599-608

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Am J Physiol Lung Cell Mol Physiol, 2014, 307(2):L173-85

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Cell Cycle, 2014, 13(12):1885-901

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PLoS One, 2014, 9(9):e108758

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PLoS One, 2014, 9(7):e102741

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Oncol Lett, 2014, 7(1):121-124

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Oncotarget, 2014, 5(17):7498-511

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Cancer Res, 2013, 73(22):6722-33

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Cancer Res, 2013, 73(20):6310-22

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Arthritis Rheum, 2013,

PubMed: 23653330 ( click the link to review the publication )

Mol Cancer Res, 2013, 12(3):433-9

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Mol Cancer Res, 2013, 11(11):1326-36

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J Cell Sci, 2013, 126(Pt 5):1235-46

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J Cell Mol Med, 2013, 17(2):265-76

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Vet Comp Oncol, 2013, 10.1111/vco.12018

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Oncotarget, 2013,

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Eur J Cancer, 2012, 48(15):2417-30

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Oncogene, 2012, 31(31):3584-96

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J Med Chem, 2012, 55(17):7392-416

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Brain Pathol, 2012, 23(3):244-53

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J Neurosci, 2012, 32(32):11050-66

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Biochem Pharmacol, 2012, 83(9):1217-28

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Biochem J, 2012, 447(1):93-102

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Exp Cell Res, 2012, 318(4):336-49

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Cytoskeleton, 2012, 69(10):840-53

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J Biomol Screen, 2012, 18(4):388-99

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Pediatr Surg Int, 2012, 28(6):579-89

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Curr Biol, 2011, 21(16):1356-65

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Cancer Res, 2011, 71(23):7207-15

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J Biol Chem, 2011, 286(42):36304-15

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Biochem J, 2011, 440(1):85-93

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Mol Cancer Ther, 2010, 9(5):1318-27

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Purity & Quality Control

Choose Selective Aurora Kinase Inhibitors

Biological Activity

Description

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	Activity Description	PMID
BE-13	NEPFcFlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NGm1UZJKSzVyPUCuNFA{OzhizszN	Mn;wQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
RS4-11	NXzadWdKT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			M1P2R2lEPTB;MD6wNFQxPCEQvF2=	NYHh[GlPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
MFH-ino	MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MUjJR\|UxRTBwMEC5PUDPxE1?	MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
NTERA-S-cl-D1	NFrs[I1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NFjsW4ZKSzVyPUCuNFE1OzRizszN	NIf0dIc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
697	MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			M1m5fmlEPTB;MD6wNlQ4OSEQvF2=	MnKwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
NALM-6	NV23NI4xT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			M1HLUmlEPTB;MD6wNlU2OiEQvF2=	NHnCS4U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
ES8	M{PYNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			M37KNmlEPTB;MD6wOFYyOyEQvF2=	MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
HUTU-80	MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			M2D6bmlEPTB;MD6wOVI6QSEQvF2=	MoDxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
MV-4-11	MnrBS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NIXRfY1KSzVyPUCuNFc4QDJizszN	NWm3SWtqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
MONO-MAC-6	MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MkTGTWM2OD1yLkC3PFc6KM7:TR?=	NVnPNolYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
LC-2-ad	MnfOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MlPJTWM2OD1yLkC4O\|g6KM7:TR?=	M{PJVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
BL-41	NGPGSIlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MW\JR\|UxRTBwMUC0OFUh\|ryP	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
A4-Fuk	MkHpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NIHrOJZKSzVyPUCuNVE2PjNizszN	NGLaXHo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
SW954	MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NXPCbmxNUUN3ME2wMlEzOjJ7IN88US=>	MlLqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
BV-173	MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MVTJR\|UxRTBwMUK2OFEh\|ryP	MkH1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
TE-11	NH7neWhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M1fOSmlEPTB;MD6xOFk5OiEQvF2=	MmjaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
SK-UT-1	MVXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			M2DCOGlEPTB;MD6xOVk3PSEQvF2=	NYrIRpJnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
SIG-M5	NHrleXVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M2LFdWlEPTB;MD6xOlcxPyEQvF2=	M4nUSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
OCUB-M	MmLKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MnrRTWM2OD1yLkG2PVg{KM7:TR?=	M2fzUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
K052	NH70S4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M3HrRWlEPTB;MD6xPVQ5KM7:TR?=	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
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SW982	NXTtSWpwT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NXLSUYo3UUN3ME2wMlIyOzhizszN	MmDaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
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HOP-62	MV;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NGWxVXZKSzVyPUCuPFY{OjlizszN	MnHNQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
TGBC24TKB	NVrVb45tT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			M1LwZWlEPTB;MD64OlM5PSEQvF2=	M1P1N\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
HCE-4	M1\xOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NF7oNWNKSzVyPUCuPFgxPjNizszN	MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
ALL-PO	NH7hT4VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NVLuUIU3UUN3ME2wMlg5OTd3IN88US=>	NELpemU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
KGN	NUTGOHk1T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NVPWPFlSUUN3ME2wMlg6QTl3IN88US=>	NVrOU\|ZvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
ML-2	NU\4V2hqT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			MmSxTWM2OD1yLkmwNlU6KM7:TR?=	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
ES4	M3zweWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			M3OyOWlEPTB;MD65NVEzQCEQvF2=	NFXzenM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
SF126	MljMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			M1jxSGlEPTB;MD65OFgyQSEQvF2=	NYfF[5B2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
SK-N-DZ	NGL5TldIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NYXvbZN6UUN3ME2wMlk3OTh7IN88US=>	MmXCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
HCC1187	MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NFHjcZRKSzVyPUGuNFA2ODVizszN	MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
DU-4475	NH7D[IZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NEXYXYhKSzVyPUGuNFE4PTZizszN	MonhQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
NKM-1	MmfNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NHjBelRKSzVyPUGuNFI4PzVizszN	NHraW3E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
HL-60	NH3lUoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MYnJR\|UxRTFwME[1O\|Qh\|ryP	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
SBC-1	MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			M1Tke2lEPTB;MT6xNlU1OiEQvF2=	M1f4PVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
TE-10	NULhNYVjT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			MoHxTWM2OD1zLkGyPVQ3KM7:TR?=	NUXGd3l5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
ETK-1	NFnCblVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NFfLOm1KSzVyPUGuNVM3OTNizszN	NXz0e25qRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
HAL-01	MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NVe4eJF7UUN3ME2xMlE3PzB7IN88US=>	NYfScm1WRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
BB65-RCC	M1LSXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MoflTWM2OD1zLkG4NFA2KM7:TR?=	NFHTOm49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
EW-1	NHS0SFNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MULJR\|UxRTFwMUi1OlIh\|ryP	M134e\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
SK-NEP-1	NHu2W\|JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MV7JR\|UxRTFwMkGxNVEh\|ryP	Mnu4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
SK-LMS-1	NUH3TFV3T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NXrlSYZnUUN3ME2xMlIzOjF{IN88US=>	M1HiPFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
DEL	Mmr1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			Moj4TWM2OD1zLkK1OlQ{KM7:TR?=	MmnNQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
GT3TKB	MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NHH2fnRKSzVyPUGuNlgxPTdizszN	MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
MOLT-16	M3PaTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NYPaVoNCUUN3ME2xMlM2PDB3IN88US=>	NXLiNW5TRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
CMK	M4DmbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MmH4TWM2OD1zLkSyNVE4KM7:TR?=	NYTyeI45RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
NB5	MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			Ml7BTWM2OD1zLk[0NlI6KM7:TR?=	NUTERpA2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
NCI-H1963	MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			M3jNVGlEPTB;MT63NFU5OyEQvF2=	M2\1bFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
KURAMOCHI	MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NUHzWVJEUUN3ME2xMlc5QTFzIN88US=>	MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
TE-8	NHzKSWRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MXTJR\|UxRTFwOECzOlgh\|ryP	NWG1[3l5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
NCI-H1304	NV;IVIxxT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NU\yNol[UUN3ME2xMlg{ODd\|IN88US=>	MoexQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
A101D	MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MYTJR\|UxRTFwOEezPVUh\|ryP	MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
SCLC-21H	MnnaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			M2\TdmlEPTB;MT65O\|A2PyEQvF2=	M1;5ZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
GB-1	NFzS[mZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NV60TpFCUUN3ME2yMlAyPjR5IN88US=>	NXTnUmR4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
KARPAS-45	NYTTdHJUT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NF3DdXFKSzVyPUKuNFI3PTRizszN	NFjveHo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
ATN-1	NIrNPXJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MX3JR\|UxRTJwMEK4OVgh\|ryP	NH7ZTmc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
NCI-H720	NISwOItIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			Mof1TWM2OD1{LkC2NlQ1KM7:TR?=	NIfIfFA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
RPMI-6666	M{Hncmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			M4\BUmlEPTB;Mj6xOlIxPyEQvF2=	NV;zfGY1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
NB17	M3[2ZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			M3nvSGlEPTB;Mj6yPVI4KM7:TR?=	MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
IST-SL1	MmS2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			M3z6T2lEPTB;Mj6yPVc3PSEQvF2=	NIHEUGg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
SH-4	Ml60S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NIDm[3VKSzVyPUKuN\|I1PjlizszN	NYn5RYRORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
K5	NYLXUGlCT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NFjQe4pKSzVyPUKuOFA{OTlizszN	NXHzTmNzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
OVCAR-4	MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MYPJR\|UxRTJwNE[xN{DPxE1?	NHXLNVU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
ACN	NIfPR4pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MWXJR\|UxRTJwNUCyNVMh\|ryP	NUTOboIzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
TGW	NY\QOHE4T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			Ml:xTWM2OD1{Lk[1PFMzKM7:TR?=	MlTMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
NCI-H2107	MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MYnJR\|UxRTJwOEO3NVEh\|ryP	NH\FOnE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
NCI-H82	Mlm4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MnjxTWM2OD1{LkizPFM5KM7:TR?=	MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
SK-N-FI	M3nvNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MlLoTWM2OD1{Lki2PFY5KM7:TR?=	MlOyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
LB1047-RCC	NXHnWIRGT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			MkHBTWM2OD1{Lki4NVI3KM7:TR?=	MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
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NCI-H2171	MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NWTUbI04UUN3ME2zMlkzPDJ\|IN88US=>	M1ztSlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
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MMAC-SF	MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			Ml;4TWM2OD12LkCyOFY4KM7:TR?=	NYL5eHI{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
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SW872	MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MX3JR\|UxRTRwM{SzOEDPxE1?	MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
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LU-139	MojwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MmXtTWM2OD12Lk[xPFM2KM7:TR?=	NVXLWGIzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
HC-1	NYfPem9lT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			MYDJR\|UxRTRwNkm0PVQh\|ryP	MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
COR-L279	NIj6XYlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M{D1WmlEPTB;ND63OVg6OSEQvF2=	NVvDfVFoRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
SF268	NFPWPXZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NW[wfJMxUUN3ME20Mlc6QTF4IN88US=>	NGezTJQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
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NCI-H2126	MYjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MkjJTWM2OD13Lk[0OVc1KM7:TR?=	M{f6WFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
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NCI-H1648	NF21ZXNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M2TwemlEPTB;NT64NVQ2PCEQvF2=	NV\rfGZRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
OS-RC-2	NFvsNFBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NXjRdnVPUUN3ME21Mlk5PTl5IN88US=>	MnvBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
DJM-1	NWq1PFZvT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			M1PRPWlEPTB;Nj6zOFY3PiEQvF2=	NIfFPYU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
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NCI-H1581	NXzJd5FIT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			MnXMTWM2OD14Lke4OFA2KM7:TR?=	NYTBUZg5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
UACC-257	Mo\4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MYHJR\|UxRTdwMES1NVIh\|ryP	M2L3SVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
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NCI-H1436	MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MmTKTWM2OD15Lk[5PVMzKM7:TR?=	M3r1RVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
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KALS-1	MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			Mn7rTWM2OD16LkizPFUyKM7:TR?=	M13rUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
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TC32	NXyy[XRoeUiWUzDhd5NigQ>?			NHr6W4VyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBVSzN{IHPlcIx{	MlHjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
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A549	M{TiemFvfGmycn;sbYZmemG2aY\lJIF{e2G7		NU\1UZF[PDhiaILz	MVTBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEF3NEmgZ4VtdHNiYX\0[ZIhPDhiaILzJIJ6KE2WVDDhd5NigSxiSVO1NF0{PS56zszN	NWjRT4dkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{C3NlgyOTJpPkOwO\|I5OTF{PD;hQi=>
LoVo	NITPboNCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NUTpfHNxPDhiaILz	M2rxNGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTH;Wc{Bk\WyuczDh[pRmeiB2ODDodpMh[nliTWTUJIF{e2G7LDDJR\|UxRTR3LkROwG0>	NWTQU\|NKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{C3NlgyOTJpPkOwO\|I5OTF{PD;hQi=>
HeLa	NYDvSmx1SW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		NV7VZmdoPDhiaILz	NIPLNnJCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjlUIEh[2WubIOgZYZ1\XJiNEigbJJ{KGK7IF3UWEBie3OjeTygTWM2OD12Nj6y{txO	MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODd{OEGxNkc,OzB5MkixNVI9N2F-

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	DLK / p-MKK7 / MKK7 / p-JNK / JNK ; PubMed: 23431148 Proc Natl Acad Sci U S A Western blot of the DLK pathway members in RGCs (retinal ganglion cells) 4 h after immunopanning in the presence of 0, 0.03, 0.06, 0.125, 0.25, 0.5, 1, or 2 μM tozasertib. p-AURKA / AURKA / Survivin ; PubMed: 28218735 Oncogenesis BGC823 cells were incubated with indicated doses of VX-680 for 24 h before subjected to western blotting with the indicated antibodies. Densitometry was used to quantify the Survivin and GAPDH levels. The relative expression shown (right panel) are means±s.e.m. of the ratios of Survivin to GAPDH. YAP; PubMed: 31160567 Cell Death Dis Western blot analysis of YAP protein level in A549 cells treated with indicated doses of VX-680 for 24 h. p-AKT / p-GSK3β / Cleaved caspase-3 / Cleaved PARP ; PubMed: 21600017 J Transl Med NB4-R2 cells were collected, lysed and subjected to Western blot analysis with cleaved caspase-3, cleaved-PARP, pAkt-1 (Ser473), pGSK-3β (Ser9) specific antibodies. GAPDH was used as a loading control. Data shown is a representative of three independent experiments.	23431148 28218735 31160567 21600017
Immunofluorescence	α-tubulin / Aurora-A ; PubMed: 21600017 J Transl Med The morphology of mitotic spindle was shown by immunofluorescence staining with anti-α-tubulin antibody and anti-Aur-A antibodies. Microtubules were stained as green, Aur-A protein as red, and nucleus as blue.	21600017
Growth inhibition assay	Cell viability; PubMed: 21600017 J Transl Med VX-680 significantly suppresses the proliferation in a number of leukemic cell types. OCI-AML3, NB4, HL-60 and ML-1 cells were incubated with increasing doses of VX-680 (1, 2, 5 and 10 nM) for 24 hr. Cell viability was measured by MTT assay. Data summarized three independent experiments, p < 0.05, *p < 0.01, compared to control.	21600017

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]	- Collapse 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]/K_d), where [S] = [ATP] = 2.2 mM, and K_d (of ATP to Abl) = 70 μM. These values are calculated assuming a K_d (ATP) of 70 μM for wild type and H396P Abl kinase domain.
Cell Research: ^[2]	- Collapse 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]	- Collapse Animal Models: Female athymic NCr-nu mice bearing HL-60 leukemia cells Dosages: 50 mg/kg, 75 mg/kg Administration: Administered via i.p. (Only for Reference)

References

[4] Cheetham GM, et al. Cancer Lett. 2007, 251(2), 323-329.

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Solubility (25°C)

In vitro	DMSO	93 mg/mL (200.17 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 5% DMSO+30% PEG 300+2% Tween 80+ddH2O For best results, use promptly after mixing.	3.75 mg/mL

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

Chemical Information Download Tozasertib (VX-680, MK-0457) SDF

Molecular Weight	464.59
Formula	C₂₃H₂₈N₈OS
CAS No.	639089-54-6
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CC1=CC(=NN1)NC2=CC(=NC(=N2)SC3=CC=C(C=C3)NC(=O)C4CC4)N5CCN(CC5)C

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Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL， Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation：Take μL DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2021-09-06)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT00290550	Terminated	Drug: MK0457	Carcinoma Non-Small-Cell Lung	Merck Sharp & Dohme Corp.	June 2006	Phase 2
NCT00111683	Completed	Drug: MK0457	Chronic Myelogenous Leukemia in Blast Crisis\|Lymphocytic Leukemia B Cell Acute\|Myelodysplastic Syndromes\|Myelogenous Leukemia Chronic	Merck Sharp & Dohme Corp.	June 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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Aurora Kinase Signaling Pathway Map

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.
Pan Aurora Kinase Inhibitors

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.

Related Aurora Kinase Products

Ro-3306 ^New

RO-3306 is an ATP-competitive, and selective CDK1 inhibitor with K_i of 20 nM, >15-fold selectivity against a diverse panel of human kinases. RO-3306 enhances p53-mediated Bax activation and mitochondrial apoptosis.
ML141 ^New

ML141 (CID-2950007) is demonstrated to be a potent, selective and reversible non-competitive inhibitor of Cdc42 GTPase suitable for in vitro assays, with IC50 of 200 nM and selectivity against other members of the Rho family of GTPases (Rac1, Rab2, Rab7). ML141 is associated with an increase in p38 activation and may induce p38-dependent apoptosis/senescence. ML141 also protects neuroblastoma cells from metformin-induced apoptosis.
Salirasib ^New

Salirasib (Farnesylthiosalicylic acid, FTS) is a potent competitive prenylated protein methyltransferase (PPMTase) inhibitor with K_i of 2.6 μM, which inhibits _Ras methylation. Salirasib exerts antitumor effects and induces autophagy. Salirasib exerts antitumor effects and induces autophagy. Phase 2.
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. Alisertib induces cell cycle arrest, apoptosis and autophagy. Phase 3.

Features:First orally available inhibitor of Aurora A.
Barasertib (AZD1152-HQPA)

Barasertib (AZD1152-HQPA, AZD2811, INH-34) 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. Danusertib induces apoptosis, cell cycle arrest, and autophagy. 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. MK-5108 (VX-689) induces autophagy. Phase 1.
Aurora A Inhibitor I (TC-S 7010)

Aurora A Inhibitor I (TC-S 7010) 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. Aurora A Inhibitor I (TC-S 7010) triggers apoptosis through the ROS-mediated UPR signaling pathway.

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

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Tozasertib (VX-680, MK-0457)