Tozasertib (VX-680, MK-0457)

Name: Tozasertib (VX-680, MK-0457)
Brand: Selleck Chemicals
SKU: S1048
Rating: 5 (102 reviews)

For research use only.

Catalog No.S1048

102 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 102 publications

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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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PLoS Biol, 2021, 19(1):e3001029

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

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

STAR Protoc, 2021, 2(3):100495

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J Clin Invest, 2020, 139080

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

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

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

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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

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Toxicol Sci, 2020, kfaa103

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

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

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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

PubMed: 31097686 ( click the link to review the publication )

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

PubMed: 30702769 ( click the link to review the publication )

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)

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Cell Signal, 2018, 52:137-146

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

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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

PubMed: 28739871 ( click the link to review the publication )

Cell Signal, 2017, 39:74-83

PubMed: 28780319 ( click the link to review the publication )

Nat Chem Biol, 2016, 10.1038/nchembio.2017

PubMed: 26829474 ( click the link to review the publication )

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

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

PubMed: 27138904 ( click the link to review the publication )

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

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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

PubMed: 26228240 ( click the link to review the publication )

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

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

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

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Oncol Rep, 2015, 34(2):803-10

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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

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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,

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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	MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NFz6[JhKSzVyPUCuNFA{OzhizszN	NHvydnE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
RS4-11	NHvWdlhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NWnPOJRTUUN3ME2wMlAxPDB2IN88US=>	M4fq[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
MFH-ino	MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NE\hdJBKSzVyPUCuNFA6QSEQvF2=	MlK4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
NTERA-S-cl-D1	M1LJOWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MlLlTWM2OD1yLkCxOFM1KM7:TR?=	M3j2R\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
697	MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			M{nBNWlEPTB;MD6wNlQ4OSEQvF2=	NWLlb2dDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
NALM-6	MmPMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NFWzSIJKSzVyPUCuNFI2PTJizszN	M3PNUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
ES8	NFL6OplIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NF7PUnJKSzVyPUCuNFQ3OTNizszN	Mki1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
HUTU-80	MljpS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MmfkTWM2OD1yLkC1Nlk6KM7:TR?=	MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
MV-4-11	M1PaXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MknCTWM2OD1yLkC3O\|gzKM7:TR?=	MnXRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
MONO-MAC-6	NVLJbnA{T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			MYHJR\|UxRTBwMEe4O\|kh\|ryP	M4nWPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
LC-2-ad	MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MnPiTWM2OD1yLkC4O\|g6KM7:TR?=	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
BL-41	M{fQU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MnWxTWM2OD1yLkGwOFQ2KM7:TR?=	NVHO[mVkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
A4-Fuk	NGDyRodIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M4\mUGlEPTB;MD6xNVU3OyEQvF2=	NEjtTnA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
SW954	MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MWHJR\|UxRTBwMUKyNlkh\|ryP	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
BV-173	NFT2XIZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NUjZUno5UUN3ME2wMlEzPjRzIN88US=>	MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
TE-11	M{P1NGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			M2LufWlEPTB;MD6xOFk5OiEQvF2=	M{PlT\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
SK-UT-1	NF\Ue5hIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M4SycWlEPTB;MD6xOVk3PSEQvF2=	Mlz4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
SIG-M5	MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MnTaTWM2OD1yLkG2O\|A4KM7:TR?=	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
OCUB-M	MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NGX0XmZKSzVyPUCuNVY6QDNizszN	MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
K052	MoDoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NXX1b4d2UUN3ME2wMlE6PDhizszN	MlPOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
VA-ES-BJ	M4LwVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NH:0cYxKSzVyPUCuNlAxQDZizszN	MoXFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
SW982	MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MX7JR\|UxRTBwMkGzPEDPxE1?	MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
LB647-SCLC	M3W1WWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NX\GN4tqUUN3ME2wMlIyPTJ\|IN88US=>	NVrsdW1MRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
PSN1	MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			M1;YS2lEPTB;MD6yNlAzPiEQvF2=	NHi1Rok9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
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HCE-4	NYKzfIFIT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NGfueIhKSzVyPUCuPFgxPjNizszN	NH\MU2g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
ALL-PO	M2jYb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7			Mki1TWM2OD1yLki4NVc2KM7:TR?=	Mn35QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
KGN	NXnWZ4l4T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NHLRWZhKSzVyPUCuPFk6QTVizszN	M3nOVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
ML-2	NGfqSIhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MUTJR\|UxRTBwOUCyOVkh\|ryP	NGjN[mg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
ES4	MX3Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NHX1cJZKSzVyPUCuPVEyOjhizszN	Mlj1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
SF126	M3\te2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7			M3\N[mlEPTB;MD65OFgyQSEQvF2=	M2fRU\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
SK-N-DZ	MnGyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			M3jD[GlEPTB;MD65OlE5QSEQvF2=	NYS0TIpnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
HCC1187	NWrMNVFGT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			M4PydWlEPTB;MT6wNFUxPSEQvF2=	MoTIQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
DU-4475	M{PzTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NV\XXnZEUUN3ME2xMlAyPzV4IN88US=>	MnfXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
NKM-1	MlqxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NVzQUFJVUUN3ME2xMlAzPzd3IN88US=>	M{HZRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
HL-60	MV\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			M{XBSGlEPTB;MT6wOlU4PCEQvF2=	MoT4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
SBC-1	M1LH[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NEnOO2tKSzVyPUGuNVI2PDJizszN	NYD4VIRKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
TE-10	MnOzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NG\OXm1KSzVyPUGuNVI6PDZizszN	M2TaW\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
ETK-1	NWHzVZhqT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			MX3JR\|UxRTFwMUO2NVMh\|ryP	NHTHN5o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
HAL-01	MUXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NIrLc2VKSzVyPUGuNVY4ODlizszN	M3fscVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
BB65-RCC	MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NVG5dVFCUUN3ME2xMlE5ODB3IN88US=>	NYnOfmJ5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
EW-1	Mm\LS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NHr2TpJKSzVyPUGuNVg2PjJizszN	NGnrR2g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
SK-NEP-1	MlHYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MVnJR\|UxRTFwMkGxNVEh\|ryP	MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
SK-LMS-1	MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			M2nxS2lEPTB;MT6yNlIyOiEQvF2=	M2DQdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
DEL	M1\DVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NGWxPFBKSzVyPUGuNlU3PDNizszN	MoC0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
GT3TKB	MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NGnMXYhKSzVyPUGuNlgxPTdizszN	M{TyflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
MOLT-16	Mn3KS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MoPNTWM2OD1zLkO1OFA2KM7:TR?=	NY\YT3B1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
CMK	NYX0UW5XT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			M3HremlEPTB;MT60NlEyPyEQvF2=	MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
NB5	M2Lw[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NH\1RWVKSzVyPUGuOlQzOjlizszN	M1jjeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
NCI-H1963	MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NUTqZ\|Y2UUN3ME2xMlcxPTh\|IN88US=>	MnzjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
KURAMOCHI	NFz0NIlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NVzHZ2F7UUN3ME2xMlc5QTFzIN88US=>	Mn\WQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
TE-8	Mmm0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			Mn:zTWM2OD1zLkiwN\|Y5KM7:TR?=	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
NCI-H1304	MlvlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			M2rYZmlEPTB;MT64N\|A4OyEQvF2=	MkLSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
A101D	M4DIXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NIHOOlFKSzVyPUGuPFc{QTVizszN	MnnIQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
SCLC-21H	NFLuTVhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NXLDSZllUUN3ME2xMlk4ODV5IN88US=>	NYfmU3I1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
GB-1	M{n5XWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MUHJR\|UxRTJwMEG2OFch\|ryP	MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
KARPAS-45	NXjUZo5QT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NGfNc3hKSzVyPUKuNFI3PTRizszN	NFX2e\|U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
ATN-1	MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NWfJWnc1UUN3ME2yMlAzQDV6IN88US=>	MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
NCI-H720	NWjINYNMT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NWe4WZJUUUN3ME2yMlA3OjR2IN88US=>	NIn0WVI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
RPMI-6666	MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MkXBTWM2OD1{LkG2NlA4KM7:TR?=	M{DUXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
NB17	MnL5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MlXtTWM2OD1{LkK5Nlch\|ryP	NGT1dJY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
IST-SL1	NFSzVnRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MYLJR\|UxRTJwMkm3OlUh\|ryP	NHXVeVY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
SH-4	NEK4UlhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MkjGTWM2OD1{LkOyOFY6KM7:TR?=	NHfScVU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
K5	NFz2clZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M1XsXmlEPTB;Mj60NFMyQSEQvF2=	NHfNVXI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
OVCAR-4	M1jGN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MVHJR\|UxRTJwNE[xN{DPxE1?	NH7EemY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
ACN	NEK0ZlNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NULtelVbUUN3ME2yMlUxOjF\|IN88US=>	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
TGW	MWDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MWLJR\|UxRTJwNkW4N\|Ih\|ryP	MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
NCI-H2107	NF7p[pBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NF[w[XVKSzVyPUKuPFM4OTFizszN	MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
NCI-H82	M3vnfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MWHJR\|UxRTJwOEO4N\|gh\|ryP	NEDNRYE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
SK-N-FI	NIP3TmlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MXrJR\|UxRTJwOE[4Olgh\|ryP	MnPJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
LB1047-RCC	MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MkTaTWM2OD1{Lki4NVI3KM7:TR?=	M1XHW\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
LU-134-A	MnrtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			M3r4TWlEPTB;Mj64PVI3KM7:TR?=	NFnyeIQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
NCI-H209	M{jWOGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NVr0eG96UUN3ME2yMlkyOjV\|IN88US=>	MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
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NCI-H2126	MXXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NF\lfIlKSzVyPUWuOlQ2PzRizszN	M3z0ZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
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NCI-H1648	NHvCUGNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MWHJR\|UxRTVwOEG0OVQh\|ryP	NXjz[oxuRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNPTd{OEe4M{c,W0GQR2LFVlww[T5?
OS-RC-2	NGrYW\|BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M4\Cb2lEPTB;NT65PFU6PyEQvF2=	MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
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NCI-H1581	NIjOeZNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MWnJR\|UxRTZwN{i0NFUh\|ryP	MnfZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMOVczQDd6Lze+V2FPT1KHUkyvZV4>
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NCI-H1436	MnXXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MlruTWM2OD15Lk[5PVMzKM7:TR?=	NGHBcpI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmw2PzJ6N{ivK\|5USU6JUlXSQE9iRg>?
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NCI-H526	MmTxS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MYrJR\|UxRThwMkW2N\|ch\|ryP	M4LPV\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFU4Ojh5OD:nQnNCVkeURWK8M4E,
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CP67-MEL	MonPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NXLyW5hQUUN3ME24MlU{OjZizszN	MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
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NCI-H1770	NGTNOmxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M{\KW2lEPTB;OD65NFI3PSEQvF2=	MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQly1O\|I5PzhxJ{7TRW5IWkWUPD;hQi=>
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A431	NHKw[FFCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NVz6ZmxJPzJiaILz	MVrBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEF2M{GgZ4VtdHNiYYPz[ZN{\WRiYYOgZ4VtdCC4aXHibYxqfHliYX\0[ZIhPzJiaILzJIJ6KEOFS{igZZN{[XluIFnDOVA:OC5{NN88US=>	MkjQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4OEGwOlYoRjJ2NkixNFY3RC:jPh?=
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HCT8	MkHzR5l1d3SxeHnjbZR6KGG\|c3H5		NV3RWWs3PDhiaILz	NYfwPG1CS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hUEOWODDj[YxteyCjZoTldkA1QCCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwQVQ1NjcQvF2=	M4L3dlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEGyPVY4Lz5{NUixNlk3PzxxYU6=
Hela	Mof6SpVv[3Srb36gZZN{[Xl?			NWHVfGx7UW6qaXLpeIlwdiCxZjDy[YNwdWKrbnHueEBCfXKxcnGgRUBscW6jc3Wg[IVzcX[nZDDmdo9uKGi3bXHuJGhmdGFiY3XscJMhfXOrbnegb4VueHSrZHWgZZMhe3Wkc4TyZZRmKGmwIIDy[ZNmdmOnIH;mJHtkNTN{UG3BWHAtKEurPUCuNFAz\|ryP	NEHoTGM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{i4OFY6Pyd-Mke4PFQ3QTd:L3G+
NCI-H23	M4XhSWFvfGmycn;sbYZmemG2aY\lJIF{e2G7			NIHVPI1CdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF7DTU1JOjNiY3XscJMhcGG{Yn;ybY5oKEuUQWOgS\|EzSyCvdYThcpQh[XR?	M4HCO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6MEO4PVQxLz5{OECzPFk1ODxxYU6=
NCI-H358	Mo\2RY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?			NHiyN4tCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF7DTU1JOzV6IHPlcIx{KGijcnLvdolv\yCNUlHTJGcyOkNibYX0ZY51KGG2	NHX5b\|E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OECzPFk1OCd-MkiwN\|g6PDB:L3G+
U937	MUnBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		MY[0PEBpenN?	M13xUmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iVUmzO{Bk\WyuczDh[pRmeiB2ODDodpMh[nliQ1PLPEBie3OjeTygTWM2OD1yLkCzOu69VQ>?	Mm\BQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl\|NUixOFcoRjJ7M{W4NVQ4RC:jPh?=
K562	M3TqNWFvfGmycn;sbYZmemG2aY\lJIF{e2G7		NG[zOno1QCCqcoO=	MUTBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEt3NkKgZ4VtdHNiYX\0[ZIhPDhiaILzJIJ6KEOFS{igZZN{[XluIFnDOVA:OC5yN{pOwG0>	MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTN3OEG0O{c,Ojl\|NUixOFc9N2F-
MDA-MB-231	MVrBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		M1PnWFQ5KGi{cx?=	M4DqXmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTVTBMW1DNTJ\|MTDj[YxteyCjZoTldkA1QCCqcoOgZpkhS0ONODDhd5NigSxiSVO1NF0xNjF{N988US=>	NGLnWlA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUO1PFE1Pyd-MkmzOVgyPDd:L3G+
A431	NVzsS29oSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		M2fOVlQ5KGi{cx?=	NVrlbHhZSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDBOFMyKGOnbHzzJIFnfGW{IES4JIhzeyCkeTDDR2s5KGG\|c3H5MEBKSzVyPUCuNlTPxE1?	M2TnRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7M{W4NVQ4Lz5{OUO1PFE1PzxxYU6=
MCF7	NHvlUmFCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		M3iyZ\|Q5KGi{cx?=	M2fEc2FvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTVPGO{Bk\WyuczDh[pRmeiB2ODDodpMh[nliQ1PLPEBie3OjeTygTWM2OD1zLkROwG0>	MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTN3OEG0O{c,Ojl\|NUixOFc9N2F-
HeLa	MnPIRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		NHe4[Wk1QCCqcoO=	MnruRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCKZVzhJINmdGy\|IHHmeIVzKDR6IHjyd{BjgSCFQ1u4JIF{e2G7LDDJR\|UxRTJwOUROwG0>	M4PGNVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7M{W4NVQ4Lz5{OUO1PFE1PzxxYU6=
HCT116	NGrkeFBCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		MXm0PEBpenN?	M1L2dGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFPUNVE3KGOnbHzzJIFnfGW{IES4JIhzeyCkeTDDR2s5KGG\|c3H5MEBKSzVyPUSuN\|LPxE1?	M2Hv[FxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7M{W4NVQ4Lz5{OUO1PFE1PzxxYU6=
TC32	M1nSRpFJXFNiYYPzZZk>			MmXTdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFSFM{KgZ4VtdHN?	MmPWQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
A673	MVXxTHRUKGG\|c3H5			MnX3dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEF4N{OgZ4VtdHN?	MnTKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-MC	NFjrNIpyUFSVIHHzd4F6			MljvdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFONLV6tUWMh[2WubIO=	NWDMSW4yRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB-EBc1	NYnIbZRleUiWUzDhd5NigQ>?			NEj6XVJyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKtSWJkOSClZXzsdy=>	NFHReYk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SK-N-SH	MYHxTHRUKGG\|c3H5			M3PpNJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMXNJKGOnbHzz	NV7tS5NHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB1643	MVrxTHRUKGG\|c3H5			MofwdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6EMU[0N{Bk\Wyucx?=	MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
LAN-5	NEL4XZNyUFSVIHHzd4F6			Mnu1dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEyDTj21JINmdGy\|	MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
BT-12	M4j3[pFJXFNiYYPzZZk>			M3;jeZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCEVD2xNkBk\Wyucx?=	NFfoSnQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
Rh18	MnXjdWhVWyCjc4PhfS=>			Mn\RdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKqMUigZ4VtdHN?	NEj2Zpk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
OHS-50	MYXxTHRUKGG\|c3H5			MXLxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhV0iVLUWwJINmdGy\|	Mm\vQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
RD	M4[xS5FJXFNiYYPzZZk>			NVrveWlbeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLEJINmdGy\|	MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
MG 63 (6-TG R)	MYXxTHRUKGG\|c3H5			M3v5bZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCPRzC2N{ApPi2WRzDSLUBk\Wyucx?=	M2nIW\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Rh30	M{PCNpFJXFNiYYPzZZk>			NEPBTIpyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUnizNEBk\Wyucx?=	MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Rh41	MVTxTHRUKGG\|c3H5			NXf5Z4JVeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLoOFEh[2WubIO=	NXrufJRSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB1643	NF22PHlyUFSVIHHzd4F6			NEnQeppyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBPSjF4NEOgZ4VtdHN?	NWfSO\|NtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
A673	MXrxTHRUKGG\|c3H5			NF35dXJyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBCPjd\|IHPlcIx{MQ>?	NH\HXZQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SK-N-MC	M33rRpFJXFNiYYPzZZk>			NWDCSGlTeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhW0tvTj3NR{Bk\Wyucx?=	NUfocYtnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
DAOY	M{X1eJFJXFNiYYPzZZk>			M{jwXpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJGRCV1liY3XscJM>	MoK5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
TC32	M{\lb5FJXFNiYYPzZZk>			MlPPdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgWGM{OiClZXzsdy=>	NWjIcIdyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
MG 63 (6-TG R)	MX7xTHRUKGG\|c3H5			M2TPNZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJG1IKDZ\|IDi2MXRIKFJrIHPlcIx{	NHOzV2M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
U-2 OS	MX;xTHRUKGG\|c3H5			NWHxdHR2eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhXS1{IF;TJINmdGy\|	MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Rh41	NIjnPIdyUFSVIHHzd4F6			MXvxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDSbFQyKGOnbHzz	NUX2VHVWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh30	M1rneZFJXFNiYYPzZZk>			NHruZoJyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBTcDNyIHPlcIx{	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Saos-2	NFf2cYpyUFSVIHHzd4F6			M2\ofZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHNid3NvMjDj[Yxtew>?	NXPTfVVGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
OHS-50	NGTlSnlyUFSVIHHzd4F6			NFO3OmhyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBQUFNvNUCgZ4VtdHN?	M4\nPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-SH	M4HReJFJXFNiYYPzZZk>			MXPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDTT{1PNVOKIHPlcIx{	MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
L929sA	Mn;hSpVv[3Srb36gZZN{[Xl?		M2C3RVI1KGi{cx?=	NGDtNHRKdmirYnn0bY9vKG:oIFH1doshdW:3c3WgUFkzQXODIHPlcIx{KHS{YX7z[oVkfGWmIIfpeIghcHWvYX6gSoF{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDpckBk\WyuIHfyc5d1cCCjZoTldkAzPCCqcoOgbY4heHKnc3XuZ4Uhd2ZiVF7GJIJ6KEixZXPod5QhOzN\|NEKgd5RicW6rbnetZoF{\WRibXnjdo9{[2:yaXOgZZN{[XluIFnDOVA:OC57N988US=>	Ml[3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{ezPFYoRjJ7NEO3N\|g3RC:jPh?=
L929sA	NWfxVXZoTnWwY4Tpc44h[XO\|YYm=		NYDuXFJuOC53IHjydy=>	MX7Jcohq[mm2aX;uJI9nKFKLUFuxJIlvKG2xdYPlJGw6Ojm\|QTDj[YxteyC2cnHud4Zm[3SnZDD3bZRpKGi3bXHuJGZieyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJIlvKFSQRj3pcoR2[2WmIH7lZ5JweHSxc3nzJJBz\XS{ZXH0[YQh\m:{IECuOUBpenNiZn;scI94\WRiYomgWG5HKGGwZDD6WmFFNm[vazDh[IRqfGmxbjDt[YF{fXKnZDDh[pRmeiB\|IHjyd{BjgSCKb3XjbJN1KDN\|M{SyM5Bzd3CrZHn1cUBqd2SrZHWgd5RicW6rbnetZoF{\WRiYYPzZZktKEmFNUC9NE46QM7:TR?=	Mo\1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{ezPFYoRjJ7NEO3N\|g3RC:jPh?=
L929sA	Mk\YSpVv[3Srb36gZZN{[Xl?		MXqyOEBpenN?	M{jJS2lvcGmkaYTpc44hd2ZiUlnQT\|EhcW5ibX;1d4UhVDl{OYPBJINmdGy\|IITyZY5{\mWldHXkJJdqfGhiaIXtZY4hTmG\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hcW5iVF7GMYlv\HWlZXSgcoVkem:ydH;zbZMheHKndILlZZRm\CCob4KgNlQhcHK\|IH\vcIxwf2WmIHL5JHRPTiCjbnSgfnZCTC6obXugZYRlcXSrb36gcYVie3W{ZXSgZYZ1\XJiMzDodpMh[nliSH;lZ4h{fCB\|M{O0Nk9xem:yaXTpeY0hcW:maXTlJJN1[WmwaX7nMYJie2WmIHHzd4F6NCCLQ{WwQVEvODMQvF2=	NUTWVnVwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|c{QDZpPkK5OFM4Ozh4PD;hQi=>
L929sA	MXnGeY5kfGmxbjDhd5NigQ>?		MV[yOEBpenN?	MWnJcohq[mm2aX;uJI9nKEG3cnugcY92e2ViTEmyPZNCKGOnbHzzJJRz[W6\|ZnXjeIVlKHerdHigbJVu[W5iRnHzJIF{e2W\|c3XkJIF{KGmwY4LlZZNmKGmwIH71Z4xm[XJiYYLlZUBi\nSncjCyOEBpenNiaX6gdJJme2WwY3Wgc4YhXE6IIHL5JGhw\WOqc4SgN\|M{PDJic4ThbY5qdmdvYnHz[YQhdWmlcn;zZ49xcWNiYYPzZZktKEmFNUC9NU4xPs7:TR?=	NUS4PZFzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|c{QDZpPkK5OFM4Ozh4PD;hQi=>
HCT116	M{jtVWN6fG:2b4jpZ4l1gSCjc4PhfS=>		NW\LSVhjPDhiaILz	NGLydGJEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBJS1RzMU[gZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKGOnbHygeoli[mmuaYT5JIFnfGW{IES4JIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTB;MD60Oe69VQ>?	NH3LT4s9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEG0N\|QzOyd-M{CxOFM1OjN:L3G+
HCT15	Mn34R5l1d3SxeHnjbZR6KGG\|c3H5		M1TJUFQ5KGi{cx?=	NGmyWVBEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBJS1RzNTDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gbY4h[2WubDD2bYFjcWyrdImgZYZ1\XJiNEigbJJ{KGK7IF3UWEBie3OjeTygTWM2OD1zLkKz{txO	M{X3RlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMUSzOFI{Lz5\|MEG0N\|QzOzxxYU6=
HCT116	MYDGeY5kfGmxbjDhd5NigQ>?	NILqcZMyODBibl2=	NIT5U5YzPCCqcoO=	MWLJcohq[mm2aX;uJI9nKGO7dH;rbY5me2m\|IHnuJIh2dWGwIFjDWFEyPiClZXzsd{BifCBzMECgcm0h[W[2ZYKgNlQhcHK\|IHL5JJBzd3CrZHn1cUBqd2SrZHWvVm5ie2Vic4ThbY5qdmdvYnHz[YQh\myxdzDjfZRwdWW2cnnjJIFv[Wy7c3nz	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODF2M{SyN{c,OzBzNEO0NlM9N2F-
HCT116	MXvGeY5kfGmxbjDhd5NigQ>?	M{jEbVEhfU1?	NX31e4xyOjRiaILz	NFm5N3JKdmirYnn0bY9vKG:oIHP5eI9scW6nc3nzJIlvKGi3bXHuJGhEXDFzNjDj[YxteyCjdDCxJJVOKGGodHXyJFI1KGi{czDifUBxem:yaXTpeY0hcW:maXTlM3JP[XOnIIP0ZYlvcW6pLXLhd4VlKG[ub4egZ5l1d22ndILpZ{BidmGueYPpdy=>	MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODF2M{SyN{c,OzBzNEO0NlM9N2F-
HCT116	MXXGeY5kfGmxbjDhd5NigQ>?	NHe1ZnQyKHWP	M1jUOFMhcHK\|	NUjJSHR7UW6qaXLpeIlwdiCxZjDBeZJwemFiQjDpckBpfW2jbjDIR3QyOTZiY3XscJMh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJIhqe3SxbnWgTFMheGixc4Doc5J6dGG2aX;uJIF1KFOnckGwJJJme2mmdXWgeZAhfG9iMTD1UUBi\nSncjCzJIhzeyCkeTDX[ZN1\XKwIHLsc5Qh[W6jbInzbZM>	MnHDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzBzNEO0NlMoRjNyMUSzOFI{RC:jPh?=
HCT116	M13kOGZ2dmO2aX;uJIF{e2G7		M2rxRVMhcHK\|	NH\ifI9KdmirYnn0bY9vKG:oIFH1do9z[SCDIIDoc5NxcG:{eXzheIlwdiCjdDDUbJIzQDhicnXzbYR2\SCrbjDoeY1idiCKQ2SxNVYh[2WubIOgeZAhfG9iMTD1UUBi\nSncjCzJIhzeyCkeTDX[ZN1\XKwIHLsc5Qh[W6jbInzbZM>	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODF2M{SyN{c,OzBzNEO0NlM9N2F-
HCT116	MWXGeY5kfGmxbjDhd5NigQ>?		NYK2TFNYOyCqcoO=	NEjLfWJKdmirYnn0bY9vKG:oIFH1do9z[SCEIIDoc5NxcG:{eXzheIlwdiCjdDDUbJIzOzJicnXzbYR2\SCrbjDoeY1idiCKQ2SxNVYh[2WubIOgeZAhfG9iMTD1UUBi\nSncjCzJIhzeyCkeTDX[ZN1\XKwIHLsc5QhdWW2aH;k	NUS2VpdRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CxOFM1OjNpPkOwNVQ{PDJ\|PD;hQi=>
Sf9	NHvKNmlHfW6ldHnvckBie3OjeR?=			NIXqeJRKdmirYnn0bY9vKG:oIFfTWE11[WepZXSgRXVTV1KDIFGgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO\|ZXSgbY4h[mGldXzveolzfXNiaX7m[YN1\WRiU3[5JINmdGy\|IIXzbY5oKE2EUDDhd{B{fWK\|dILheIUtKEmFNUC9NE4xOjQQvF2=	M3jTb\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMkO0PVg4Lz5\|MEKzOFk5PzxxYU6=
HeLa	NECyNlhHfW6ldHnvckBie3OjeR?=		NH:5[3YyOiCqcoO=	NFLFTo5KdmirYnn0bY9vKG:oIFH1do9z[SCDIIDoc5NxcG:{eXzheIlwdiCjdDDUbJIzQDhicnXzbYR2\SCrbjDoeY1idiCKZVzhJINmdGy\|IHHmeIVzKDF{IHjyd{BjgSCHTFnTRUwhUUN3ME2wMlAyO87:TR?=	NIfBNnY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEWwNlEyPSd-M{C1NFIyOTV:L3G+
HeLa	Mo\LSpVv[3Srb36gZZN{[Xl?		MV[xNkBpenN?	MoSxTY5pcWKrdHnvckBw\iCDdYLvdoEhSiCyaH;zdIhwenmuYYTpc44h[XRiVHjyNlMzKHKnc3nkeYUhcW5iaIXtZY4hUGWOYTDj[YxteyCjZoTldkAyOiCqcoOgZpkhTUyLU1GsJGlEPTB;MD6xOFjPxE1?	NXXX[21URGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{C1NFIyOTVpPkOwOVAzOTF3PD;hQi=>
A549	NFPxUIdCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NEGzcmM1QCCqcoO=	MlfYRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCDNUS5JINmdGy\|IHHmeIVzKDR6IHjyd{BjgSCPVGSgZZN{[XluIFfJOVA:OzVwON88US=>	MnjyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB3MEKxNVUoRjNyNUCyNVE2RC:jPh?=
LoVo	MYnBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		MXq0PEBpenN?	MVPBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEyxVn:gZ4VtdHNiYX\0[ZIhPDhiaILzJIJ6KE2WVDDhd5NigSxiR1m1NF01PS5\|zszN	NIK3NGc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEWwNlEyPSd-M{C1NFIyOTV:L3G+
HeLa	Mkn1RY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		NXTCVVhrPDhiaILz	MoewRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCKZVzhJINmdGy\|IHHmeIVzKDR6IHjyd{BjgSCPVGSgZZN{[XluIFfJOVA:PDZwMt88US=>	M2rx[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyNUCyNVE2Lz5\|MEWwNlEyPTxxYU6=
HeLa	M1m2[WNmdGxiY4njcIUh[XO\|YYm=	MnflOUB2VQ>?	MkTZNVIhcHK\|	MVHD[YxtKGO7Y3zlJIFzemW\|dDDpckBpfW2jbjDI[WxiKGOnbHzzJIF{e2W\|c3XkJIF{KGSnY4LlZZNmKGmwIHP5Z4xqdiCEMTDwdo91\WmwIHX4dJJme3Orb36gZZQhPSC3TTDh[pRmeiBzMjDodpMh[nliV3XzeIVzdiCkbH;0JIFv[Wy7c3nz	MmToQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB3MEKxNVUoRjNyNUCyNVE2RC:jPh?=
HeLa	MWPD[YxtKGO7Y3zlJIF{e2G7	M2rOW\|UhfU1?	MV2xNkBpenN?	M1nKTGNmdGxiY4njcIUh[XK{ZYP0JIlvKGi3bXHuJGhmVGFiY3XscJMh[XO\|ZYPz[YQh[XNiZHXjdoVie2ViaX6gZ4RkOiCycn;0[YlvKGW6cILld5Nqd25iYYSgOUB2VSCjZoTldkAyOiCqcoOgZpkhX2W\|dHXyckBjdG:2IHHuZYx6e2m\|	NGnpe289[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEWwNlEyPSd-M{C1NFIyOTV:L3G+
HeLa	M4XJV2Z2dmO2aX;uJIF{e2G7	MmezOUB2VQ>?	M2rGSFEzKGi{cx?=	MmPmTY5pcWKrdHnvckBw\iCDdYLvdoEhSSCyaH;zdIhwenmuYYTpc44h[XRiVHjyNlg5KHKnc3nkeYUhcW5iaIXtZY4hUGWOYTDj[YxteyCjdDC1JJVOKGGodHXyJFEzKGi{czDifUBY\XO2ZYLuJIJtd3RiYX7hcJl{cXN?	NUPMRVdyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{C1NFIyOTVpPkOwOVAzOTF3PD;hQi=>
HeLa	NF7QNHZHfW6ldHnvckBie3OjeR?=	Mln4OUB2VQ>?	NULkUWxiOTJiaILz	MVHJcohq[mm2aX;uJI9nKEG3cn;yZUBDKHCqb4PwbI9zgWyjdHnvckBifCCWaIKyN\|IhemW\|aXT1[UBqdiCqdX3hckBJ\UyjIHPlcIx{KGG2IEWgeW0h[W[2ZYKgNVIhcHK\|IHL5JHdme3Sncn6gZoxwfCCjbnHsfZNqew>?	M3PBelxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyNUCyNVE2Lz5\|MEWwNlEyPTxxYU6=
A549	M4HHWmFvfGmycn;sbYZmemG2aY\lJIF{e2G7		M3iy[lQ5KGi{cx?=	MkTGRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCDNUS5JINmdGy\|IHHmeIVzKDR6IHjyd{BjgSCPVGSgZZN{[XluIFnDOVA:OzVwON88US=>	NF\jOFg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEeyPFEyOid-M{C3NlgyOTJ:L3G+
LoVo	NX7NSppCSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		M1LHOlQ5KGi{cx?=	M2DIOGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iTH;Wc{Bk\WyuczDh[pRmeiB2ODDodpMh[nliTWTUJIF{e2G7LDDJR\|UxRTR3LkROwG0>	MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODd{OEGxNkc,OzB5MkixNVI9N2F-
HeLa	NV;3fFl7SW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		M4HpUVQ5KGi{cx?=	M1PWdmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSHXMZUBk\WyuczDh[pRmeiB2ODDodpMh[nliTWTUJIF{e2G7LDDJR\|UxRTR4LkNOwG0>	Ml3kQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB5MkixNVIoRjNyN{K4NVEzRC:jPh?=

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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

In vivo Formulation Calculator (Clear solution)

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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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Bio Calculators

Molarity Calculator

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The Serial Dilution Calculator Equation

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Molecular Weight Calculator

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Definitions of molecular mass, molecular weight, molar mass and molar weight:

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Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2021-05-17)

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)