Panobinostat (LBH589)

Name: Panobinostat (LBH589)
Brand: Selleck Chemicals
SKU: S1030
Rating: 5 (313 reviews)

For research use only.

Catalog No.S1030 Synonyms: NVP-LBH589

313 publications

Panobinostat (LBH589) Chemical Structure

CAS No. 404950-80-7

Panobinostat (LBH589, NVP-LBH589) is a novel broad-spectrum HDAC inhibitor with IC50 of 5 nM in a cell-free assay. Panobinostat (LBH589) induces autophagy and apoptosis. Panobinostat effectively disrupts HIV latency in vivo. Phase 3.

Selleck's Panobinostat (LBH589) has been cited by 313 publications

Nat Med, 2021, 10.1038/s41591-020-01212-6

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Cell Stem Cell, 2021, 28(1):48-62.e6

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Cell, 2020, S0092-8674(20)31394-5

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Nat Biotechnol, 2020, 10.1038/s41587-019-0388-4

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Cancer Cell, 2019, 36(2):179-193

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Cancer Cell, 2019, 36(5):528-544

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Cell, 2019, 36(2):179-193

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Cancer Cell, 2019, 35(5):782-797

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Nat Immunol, 2019, 20(7):835-851

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Nat Med, 2018, 24(11):1752-1761

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Cell, 2018, 173(6):1413-1425

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Nat Genet, 2018, 50(10):1442-1451

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Cancer Discov, 2017, 7(12):1450-1463

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Cancer Cell, 2016, 29(3):311-323

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Nat Med, 2015, 10.1038/nm.3855

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Nat Biotechnol, 2011, 29(3):255-65

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Nat Commun, 2021, 12(1):5056

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Neuro Oncol, 2021, 23(3):376-386

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Cancer Res, 2021, canres.0955.2021

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Cell Rep, 2021, 36(9):109643

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Elife, 2021, 10e63810

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Oncogene, 2021, 10.1038/s41388-021-01931-1

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Sci China Life Sci, 2021, 10.1007/s11427-020-1855-4

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Int J Cancer, 2020, 10.1002/ijc.33046

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PLoS Pathog, 2020, 16(3):e1008442

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Cancer Discov, 2020, CD-20-0756

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Am J Cancer Res, 2020, 10(6):1827-1843

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Mol Cancer Res, 2020, 18(7):1004-1017

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Front Oncol, 2020, 10:296

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Int J Mol Sci, 2020, 21(21)E8300

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Sci Rep, 2020, 10(1):3470

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Fluids Barriers CNS, 2020, 2;17(1):37

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HIV Med, 2020, 21(11):747-757

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Sci China Life Sci, 2020, 10.1007/s11427-020-1736-5

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Exp Hematol, 2020, 81:32-41

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J Thromb Haemost, 2020, 10.1111/jth.15012

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Cancer Chemother Pharmacol, 2020, 10.1007/s00280-019-04021-y

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Blood Adv, 2020, 4(18):4393-4405

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Cancer Lett, 2020, S0304-3835(20)30652-2

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EBioMedicine, 2020, 102853

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Oncogene, 2020, 10.1038/s41388-020-01408-7

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Br J Cancer, 2020, 10.1038/s41416-020-01191-y

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Mol Cancer Ther, 2020, 19(2):637-649

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Cancer Manag Res, 2020, 12:4429-4439

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Cancer Cell, 2020, 38(1):44-59.e9

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Commun Biol, 2020, 3(1):363

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Blood Adv, 2020, 4(5):819-829

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Cancer Cell, 2020, 38(6):872-890.e6

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J Med Chem, 2020, 10.1021/acs.jmedchem.9b01888

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Cancer Immunol Res, 2020, 8(6):794-805

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Cell Res, 2019, 29(4):286-304

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Nat Commun, 2019, 10(1):3319

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Clin Cancer Res, 2019, 10.1158/1078-0432

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Leukemia, 2019, 10.1038/s41375-019-0525-6

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Proc Natl Acad Sci U S A, 2019, 116(26):12986-12995

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Neuro Oncol, 2019, 10.1093/neuonc/noz215

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Cancer Immunol Res, 2019, 7(2):230-243

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Cancer Res, 2019, 79(11):2947-2961

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Haematologica, 2019, 10.3324/haematol.2018.211110

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Clin Infect Dis, 2019, 10.1093/cid/ciz108

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J Immunother Cancer, 2019, 7(1):33

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Cell Rep, 2019, 29(9):2783-2795

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Elife, 2019, 10.7554/eLife.44306

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Oncogene, 2019, 38(15):2690-2705

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J Exp Clin Cancer Res, 2019, 38(1):185

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Breast Cancer Res, 2019, 21(1):134

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Acta Pharm Sin B, 2019, 9(5):937-951

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Mol Cancer Ther, 2019, 18(5):900-908

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Biochim Biophys Acta Mol Basis Dis, 2019, 1865(6):1666-1676

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AIDS, 2019, 33(2):199-209

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Biomolecules, 2019, 9(5)

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J Neurochem, 2019, 10.1111/jnc.14935

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Mol Pharm, 2019, 16(5):1813-1826

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J Cell Physiol, 2019, 234(10):18970-18984

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Eur J Nutr, 2019, 10.1007/s00394-019-01925-6

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J Virol, 2019, 93(24)

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Antimicrob Agents Chemother, 2019, 63(2)

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Epigenetics Chromatin, 2019, 12(1):18

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Int J Mol Sci, 2019, 20(12)

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J Biol Chem, 2019, 294(12):4437-4449

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Apoptosis, 2019, 24(1-2):184-197

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Mol Carcinog, 2019, 58(12):2230-2240

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Mol Carcinog, 2019, 58(2):234-246

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Virus Res, 2019, 269:197631

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J Nanobiotechnology, 2019, 17(1):69

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Nat Commun, 2018, 9(1):4866

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Proc Natl Acad Sci U S A, 2018, 115(8):E1867-E1875

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Cancer Res, 2018, 78(5):1155-1168

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Oncogene, 2018, 37(6):722-731

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Cancer Lett, 2018, 417:152-160

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Sci Signal, 2018, 11(557)

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EBioMedicine, 2018, 28:80-89

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Cell Death Dis, 2018, 9(10):944

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Mol Cancer Ther, 2018, 17(2):381-392

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Mol Cancer Ther, 2018, 17(12):2767-2779

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Cell Oncol (Dordr), 2018, 41(2):201-212

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J Immunol, 2018, 201(3):1086-1096

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J Virol, 2018, 92(13)

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J Virol, 2018, 92(6)

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Int J Mol Sci, 2018, 19(8)

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Sci Rep, 2018, 8(1):9472

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J Proteome Res, 2018, 17(4):1436-1451

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Biomed Pharmacother, 2018, 100:509-520

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J Cell Biochem, 2018, 119(5):4193-4204

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Retrovirology, 2018, 15(1):36

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J Ethnopharmacol, 2018, 211:267-277

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Exp Cell Res, 2018, 363(2):196-207

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PLoS One, 2018, 13(12):e0208147

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Dis Markers, 2018, 2018:3810108

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Cell Biochem Funct, 2018, 36(8):398-407

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Anticancer Drugs, 2018, 29(1):61-74

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Curr Protoc Pharmacol, 2018, 81(1):e41

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Oncotarget, 2018, 9(92):36530-36541

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F1000Res, 2018, 7:1906

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Oncotarget, 2018, 9(47):28586-28598

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Nat Commun, 2017, 8(1):728

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Cancer Res, 2017, 77(11):3027-3039

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Int J Cancer, 2017, 141(9):1921-1931

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Oncogene, 2017, 36(50):6850-6862

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Stem Cell Reports, 2017,

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Cell Death Dis, 2017,

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Plant Physiol, 2017, 175(4):1760-1773

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Arch Toxicol, 2017, 91(2):839-864

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Cancer Discov, 2017, 7(12):1450-1463

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Mol Cancer Ther, 2017, 16(2):285-299

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Br J Haematol, 2017, 178(5):728-738

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Epigenetics, 2017, 12(2):105-112

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Int J Nanomedicine, 2017, 12:1385-1399

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J Biol Chem, 2017, 292(9):3683-3691

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J Pharmacol Exp Ther, 2017, 363(2):211-220

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Mol Biol Cell, 2017, 28(26):3756-3772

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J Neuropathol Exp Neurol, 2017,

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Exp Cell Res, 2017, 350(1):218-225

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Int J Parasitol Drugs Drug Resist, 2017, 7(1):42-50

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PLoS One, 2017, 12(10):e0186620

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Horm Cancer, 2017, 8(4):257-267

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Leuk Res, 2017, 56:36-43

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SLAS Discov, 2017, 22(5):507-515

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Methods Mol Biol, 2017, 1510:11-22

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Blood Adv, 2017, 1(19):1575-1583

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Oncotarget, 2017, 8(50):87307-87316

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Genom Data, 2017, 12:14-16

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Oncotarget, 2017, 8(11):17833-17848

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JCI Insight, 2017, 2(1):e85811

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Oncotarget, 2017, 9(3):3908-3921

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Oncotarget, 2017, 8(18):30019-30029

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Oncotarget, 2017, 8(34):56747-56757

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Blood, 2016, 127(10):1325-35

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Clin Cancer Res, 2016, 22(10):2534-44

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Proc Natl Acad Sci U S A, 2016, 113(46):13162-13167

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Int J Cancer, 2016, 139(1):194-204

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Oncogene, 2016, 35(46):6026-6037

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Mol Oncol, 2016, 10(5):735-750

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ACS Chem Biol, 2016, 11(10):2685-2692

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Mol Pharm, 2016, 13(11):3724-3735

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J Cell Physiol, 2016, 231(3):650-8

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Sci Rep, 2016, 6:38407

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J Biol Chem, 2016, 291(16):8745-55

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Biomed Pharmacother, 2016, 84:1393-1405

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Retrovirology, 2016, 13(1):36

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J Cancer Res Clin Oncol, 2016, 142(11):2263-73

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Leuk Lymphoma, 2016, 57(11):2644-52

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JCI Insight, 2016, 1(5):e85061

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Oncotarget, 2016,

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Ann Rheum Dis, 2015, 10.1136/annrheumdis-2014-206258

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Purity & Quality Control

Choose Selective HDAC Inhibitors

Biological Activity

Description

Targets

HDAC (MOLT-4 cells) ^[1]	HDAC (Reh cells) ^[1]
5 nM	20 nM

In vitro

LBH589 induces apoptosis among MOLT-4 and Reh cells in a time- and dose-dependent manner. Moreover, LBH589 is more potent in MOLT-4 than in Reh cells. LBH589 markedly prevents the growth of both MOLT-4 and Reh cells in a dose-dependent manner at 48 hours. LBH589 treatment causes a 2- to 3-fold increase in the number of cells in the G2/M phase of the cell cycle compared with the control cells. LBH589 is associated with induction of histone H3K9 and histone H4K8 acetylation as well as decreasing levels of c-Myc expression in a dose-dependent manner. LBH589 treatment also increases the levels of p21 expression. LBH589 treatment also decreases the levels of c-Myc after an initial increase at the lowest dose (10 nM) in Reh cells. In addition, LBH589 gives rise to substantial increases in mRNA levels of proapoptosis and DNA repair genes. LBH589 induces increased levels of acetylated histone H3 and H4 at the GADD45G promoter. ^[1] Besides, LBH589 inhibits growth of non small cell lung cancer cell lines (such as human H1299, L55 and A549 with IC50 of 5 nM, 11 nM and 30 nM, respectively), mesothelioma (such as human OK-6 and Ok-5 with IC50 of 5 nM and 7 nM, respectively) and small cell lung cancer cell lines (such as human RG-1 and LD-T with IC50 of 4 nM and 5 nM, respectively). ^[2]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
HT29	MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NHi2[Y8xNTFyIN88US=>	NGf0SlMxNTRiZB?=		M1fPWYlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHLveIghfGmvZT2gZY5lKGSxc3Wt[IVx\W6mZX70JI1idm6nch?=	Mn3wQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ5MEK3PFQoRjJ4N{CyO\|g1RC:jPh?=
HepG2	MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M4rjdlAuOTBizszN	NVLkPZd7OC12IHS=		MmP4bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYn;0bEB1cW2nLTDhcoQh\G:\|ZT3k[ZBmdmSnboSgcYFvdmW{	NWjwfmJnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[3NFI4QDRpPkK2O\|AzPzh2PD;hQi=>
HT29	NULueZRWTnWwY4Tpc44hSXO\|YYm=	MVO1NOKhdk1?	NVy1foFWOjRvN{KgbC=>		M4fYbIlv\HWlZXSgZYN1cX[jdHnvckBw\iClYYPwZZNmKDNiYX\0[ZIhPDkEoHlCpC=>	MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjdyMke4OEc,OjZ5MEK3PFQ9N2F-
HepG2	Mn;1SpVv[3Srb36gRZN{[Xl?	MnjhOVDDqG6P	MX2yOE04OiCq		MknTbY5lfWOnZDDhZ5RqfmG2aX;uJI9nKGOjc4Dhd4UhOyCjZoTldkAzPMLiaNMg	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjdyMke4OEc,OjZ5MEK3PFQ9N2F-
HCC827	NGW0U\|JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NFnrc\|M2NzdwNT:xNEBvVQ>?	NEjtb5g4OsLiaB?=	Ml3uSG1UVw>?	NFG1V5FmdmijbnPld{B1cGViYX70bZBzd2yrZnXyZZRqfmViZX\m[YN1KG:oIHXycI91cW6rYh?=	NWn3XZpMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[2O\|U1QDRpPkK2Olc2PDh2PD;hQi=>
A549	MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NXv1OoNyOTBxMUWvNlAhdk1?	M3rsUFczyqCq	MYHEUXNQ	MoPt[Y5p[W6lZYOgeIhmKGGwdHnwdo9tcW[ncnH0bZZmKGWoZnXjeEBw\iCncnzveIlvcWJ?	NIqwVYI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{Nk[3OVQ5PCd-Mk[2O\|U1QDR:L3G+
NCI-H460	MlXES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NX;qbZlvOTBxMkCvN\|Ahdk1?	MUi3NuKhcA>?	MUTEUXNQ	NGfUdndmdmijbnPld{B1cGViYX70bZBzd2yrZnXyZZRqfmViZX\m[YN1KG:oIHXycI91cW6rYh?=	NXL0NmVURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[2O\|U1QDRpPkK2Olc2PDh2PD;hQi=>
J89GFP	Mn70S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MmXTSG1UV8Li	MXfFR\|UxRTR7Lki1JOKyKDF{Lk[1JI5O	M4\hTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NU[zOVY5Lz5{NkW2N\|U3QDxxYU6=
THP89GFP	MojSS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MlPLSG1UV8Li	NFG3R5JGSzVyPUG5MlM1KMLzIE[uOFMhdk1?	MnrGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3NkO1OlgoRjJ4NU[zOVY5RC:jPh?=
SK-NEP-1	Mnq5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M4L3dFAvODIkgKOxNE4xKM7:TR?=	MYmyOEBp	MnPGSG1UV8Li	MULJR\|UxRTd4LkO0JI5O	NEPk[Y89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkG3OlIyQSd-Mk[xO\|YzOTl:L3G+
G401	NX2zZ41mT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	Mli1NE4xOeLCk{GwMlAh\|ryP	M{m2TlI1KGh?	NGj2dG9FVVORwrC=	MWLJR\|UxRTF2Mz6wNkBvVQ>?	M3fYdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUe2NlE6Lz5{NkG3OlIyQTxxYU6=
SK-NEP-1	MoD5R4VtdCCYaXHibYxqfHliQYPzZZk>	Mn60OVAhdk1?	Mkm1NgKBmzRiZB?=	MlP1SG1UV8Li	MYDy[YR2[2W\|IHPlcIwhe3W{dnn2ZYwhcW5iYTD0bY1mKGSncHXu[IVvfCCvYX7u[ZI>	MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF5NkKxPUc,OjZzN{[yNVk9N2F-
G401	MknjR4VtdCCYaXHibYxqfHliQYPzZZk>	MV21NEBvVQ>?	M1nNTVHjiJN2IHS=	M{fHNGROW00EoB?=	NEf2fIFz\WS3Y3XzJINmdGxic4Xyeol3[WxiaX6gZUB1cW2nIHTldIVv\GWwdDDtZY5v\XJ?	M3XCUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUe2NlE6Lz5{NkG3OlIyQTxxYU6=
SK-NEP-1	NE\zXoRCeG:ydH;zbZMhSXO\|YYm=	NV;nblNFPTBxMUCwJI5O	MWSyOEBp	NX3I[2ZYTE2VT9Mg	MnnNbY5lfWOnczDj[YxtKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?	MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF5NkKxPUc,OjZzN{[yNVk9N2F-
G401	MVjBdI9xfG:\|aYOgRZN{[Xl?	MoXwOVAwOTByIH7N	NX\XcZNrOjRiaB?=	M3zqSWROW00EoB?=	MnXubY5lfWOnczDj[YxtKGGyb4D0c5NqeyCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?	M3O5XlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUe2NlE6Lz5{NkG3OlIyQTxxYU6=
SK-NEP-1	NFnrVJRHfW6ldHnvckBCe3OjeR?=	Mn3FOVAwOTByIH7N	NFr3UIgzPCCq	MUjEUXNQyqB?	MVPzbI94eyC2aHWgbY5lfWO2aX;uJI9nKESQQTDmdoFodWWwdHH0bY9v	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF5NkKxPUc,OjZzN{[yNVk9N2F-
G401	M3K2Z2Z2dmO2aX;uJGF{e2G7	MnzOOVAwOTByIH7N	MlLhNlQhcA>?	NX3jWZgxTE2VT9Mg	NGnte3h{cG:5czD0bIUhcW6mdXP0bY9vKG:oIFTORUBnemGpbXXueIF1cW:w	MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF5NkKxPUc,OjZzN{[yNVk9N2F-
SK-NEP-1	NILtfZpHfW6ldHnvckBCe3OjeR?=	NHT3RWw2OC9zMECgcm0>	MmPSNlQhcA>?	MUfEUXNQyqB?	MXPpcoR2[2W\|IHPlcIwh[3mlbHWg[Il{d3KmZYNCpC=>	NYDZZlFiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xO\|YzOTlpPkK2NVc3OjF7PD;hQi=>
G401	NVvBPJkyTnWwY4Tpc44hSXO\|YYm=	M2POU\|UxNzFyMDDuUS=>	M2PybVI1KGh?	NXvjZ2V5TE2VT9Mg	MnTEbY5lfWOnczDj[YxtKGO7Y3zlJIRqe2:{ZHXyxsA>	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF5NkKxPUc,OjZzN{[yNVk9N2F-
RPMI 8226	MnOwR4VtdCCVdYL2bZZidCCDc4PhfS=>	NXfufIxPOi92L{[gcm0>	NYH5c2xTPDkkgJno		NF;hNnpqdmS3Y3XzJIEhe2mpbnnmbYNidnRiZHXjdoVie2ViaX6geIhmKGOnbHyg[5Jwf3Sq	NWjke25nRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wNFAzQTJpPkK2NFAxOjl{PD;hQi=>
OPM2	MoHJR4VtdCCVdYL2bZZidCCDc4PhfS=>	NX3lemg1Oi92L{[gcm0>	MXS0PQKBkWh?		NIDo[49qdmS3Y3XzJIEhe2mpbnnmbYNidnRiZHXjdoVie2ViaX6geIhmKGOnbHyg[5Jwf3Sq	NWL1Omw2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wNFAzQTJpPkK2NFAxOjl{PD;hQi=>
U266	NH:2fmZE\WyuIGP1dpZqfmGuIFHzd4F6	MUGyM\|QwPiCwTR?=	MVG0PQKBkWh?		M3O1VIlv\HWlZYOgZUB{cWewaX\pZ4FvfCCmZXPy[YF{\SCrbjD0bIUh[2WubDDndo94fGh?	NUjLUlA{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wNFAzQTJpPkK2NFAxOjl{PD;hQi=>
H929	MWPD[YxtKFO3co\peoFtKEG\|c3H5	MWiyM\|QwPiCwTR?=	M{XLVFQ56oDLaB?=		M{XBVYlv\HWlZYOgZUB{cWewaX\pZ4FvfCCmZXPy[YF{\SCrbjD0bIUh[2WubDDndo94fGh?	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjByMEK5Nkc,OjZyMECyPVI9N2F-
RPMI 8226	Mor6RZBweHSxc3nzJGF{e2G7	NVrtTZVFPOLCiX7N	NFr3O3UzPC92ODDo		M2j5N4lv\HWlZYOgZ4VtdCCjcH;weI9{cXNiaX6gZUB1cW2nLXTldIVv\GWwdDDtZY5v\XJ?	NXG2d4RkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wNFAzQTJpPkK2NFAxOjl{PD;hQi=>
HCC827	M{PxSGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MXOxNEBvVQ>?	M3;Cc\|Q5KGh?	NXH1fYVSTE2VTx?=	M3q2fIVvcGGwY3XzJINqe3CuYYTpckB{\W6\|aYTpeol1gcLi	M3q1VlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OUS0OlE4Lz5{NUm0OFYyPzxxYU6=
NCI-H23	NVjRVWI3T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NIf1bpoyOCCwTR?=	NV:4RnA{PDhiaB?=	M2TGTWROW09?	Mm\i[Y5p[W6lZYOgZ4l{eGyjdHnuJJNmdnOrdHn2bZR6yqB?	NWjxN2tYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW5OFQ3OTdpPkK1PVQ1PjF5PD;hQi=>
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ACHN	NFrVT4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MlrNNVAwOjVxNUCgcm0>	Mk\5OFghcA>?		MX3pcohq[mm2czDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uh\GWyZX7k[Y51KG2jbn7ldkB{gW6ncnfpd5Rq[2GubImge4l1cCC{aYTvcoF3cXJ?	MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTJ5OUG5NUc,OjV{N{mxPVE9N2F-
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Caki-1	M3\6XGFxd3C2b4Ppd{BCe3OjeR?=	MoC2OVAhdk1?	M2myUFQ5KGh?		M2HuV4lv\HWlZYOgZ4VtdCCjcH;weI9{cXNiY3;tZolv\WRicnn0c45ifmm{	Mny4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV{N{mxPVEoRjJ3Mke5NVkyRC:jPh?=
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ACHN	MmXlR49td267IF\vdo1ifGmxbjDBd5NigQ>?	MkiyOVAhdk1?	M3X2fFcuOTRiZB?=	NFOzSFFFVVOR	Mofxd5VxeHKnc4Pl[EBkd2yxbomg[o9zdWG2aX;uJJNq\26rZnnjZY51dHliY3;tZolv\WRid3n0bEB4cXSqIHLvdpRmgm:vaXKgxsA>	MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTF5NkO1OEc,OjVzN{[zOVQ9N2F-
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ACHN	MoHsRZBweHSxc3nzJGF{e2G7	M2TpXVUxKG6P	NHX0R\|Y1QCCq	NWjnWHdtTE2VTx?=	NIPydZlqdmS3Y3XzJINmdGxiYYDvdJRwe2m\|	MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTF5NkO1OEc,OjVzN{[zOVQ9N2F-
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PC3-AR	NU[zSVN2T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NWnkeGtEOC1zMECgcm0>	M1y1SlI1NzR6IHi=		M4PaRYlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgbY4hfGinIFeyUUBxcGG\|ZR?=	NHntNow9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEG2N\|I{OCd-MkSxOlMzOzB:L3G+
PC3	NGHFW3dHfW6ldHnvckBCe3OjeR?=	MWewMVExOCCwTR?=	NIH4SWozPCCq		NF;KR4x{fXCycnXzd4V{KGW6cILld5Nqd25ib3[gZYN1cX[jdHXkJGFVVSxiQXv0JIFv\CCHcnuxM\|IheHKxdHXpci=>	M1\rWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MU[zNlMxLz5{NEG2N\|I{ODxxYU6=
PC3-AR	MnH3SpVv[3Srb36gRZN{[Xl?	MVewMVExOCCwTR?=	NXLzbodwOjRiaB?=		NVLxbldje3WycILld5NmeyCneIDy[ZN{cW:wIH;mJIFkfGm4YYTl[EBCXE1uIFHreEBidmRiRYLrNU8zKHC{b4TlbY4>	NFTQOZc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEG2N\|I{OCd-MkSxOlMzOzB:L3G+
OS-RC-2	NVrr[nZmS2WubDDWbYFjcWyrdImgRZN{[Xl?	NY\ke3h7OC1zMECwJI5O	Mny0NlQwPDhxN{KgbC=>	MkezSG1UVw>?	M1:1e4Rm[3KnYYPld{Bk\WyuII\pZYJqdGm2eTDpckBjd3SqIITpcYUuKGGwZDDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>	M4HzUlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MUS0O\|M4Lz5{NEG0OFc{PzxxYU6=
OS-RC-2	MlHGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M3HxVVUxKG6P	M2LRNVQ5KGh?	M4fxd2ROW09?	M2XuNolv\HWlZYOgS\|IwVSCjcoLld5Q>	NIqzVm89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEG0OFc{Pyd-MkSxOFQ4Ozd:L3G+
OS-RC-2	MV3BdI9xfG:\|aYOgRZN{[Xl?	MXq1NEBvVQ>?	M1O1VVQ5KGh?	M1TqWmROW09?	Ml\GbY5lfWOnczDj[YxtKGGyb4D0c5Nqew>?	NV21W\|VuRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSxOFQ4OzdpPkK0NVQ1PzN5PD;hQi=>
SK-N-AS	MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NIezRpgx6oDVOECgcm0>	M1TvNVQ5KGh?		NGDVbXlKSzVyPUK3MlQhdk1?	MmD3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyOUi3PVkoRjJ2MEm4O\|k6RC:jPh?=
SK-N-DZ	NV3sWVBjT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MofPNQKBmzhyIH7N	Mmj3OFghcA>?		M4DoW2lEPTB;MkGuPUBvVQ>?	NV\Cb25FRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPVg4QTlpPkK0NFk5Pzl7PD;hQi=>
SK-N-SH	M{LXdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NF\0clAx6oDVOECgcm0>	MUW0PEBp		M2P5XGlEPTB;N{KuN{BvVQ>?	MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB7OEe5PUc,OjRyOUi3PVk9N2F-
SK-N-BE	NH3QXYpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MXmw5qCUQDBibl2=	MknhOFghcA>?		MknJTWM2OD15NT60JI5O	MnXYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyOUi3PVkoRjJ2MEm4O\|k6RC:jPh?=
SK-N-AS	MUfBdI9xfG:\|aYOgRZN{[Xl?	NYHHWJFkOOLCk{iwJI5O	NIfCdIc1QCCq		MVTwc5RmdnSueTDpcoR2[2WmIHHwc5B1d3OrczDpckBiKGSxc3Wt[IVx\W6mZX70JIZie2irb36=	MnP0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyOUi3PVkoRjJ2MEm4O\|k6RC:jPh?=
SK-N-DZ	NWXGdoZrSXCxcITvd4l{KEG\|c3H5	M{LiblDjiJN6MDDuUS=>	NEDibG41QCCq		MXnwc5RmdnSueTDpcoR2[2WmIHHwc5B1d3OrczDpckBiKGSxc3Wt[IVx\W6mZX70JIZie2irb36=	NXvBU\|FrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPVg4QTlpPkK0NFk5Pzl7PD;hQi=>
SK-N-SH	NFvXWZNCeG:ydH;zbZMhSXO\|YYm=	Mkj6NQKBmzRyIH7N	NVXvSoFYPDhiaB?=		NVfa[HpveG:2ZX70cJkhcW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCoYYPobY9v	MlzVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyOUi3PVkoRjJ2MEm4O\|k6RC:jPh?=
SK-N-BE	MYLBdI9xfG:\|aYOgRZN{[Xl?	M4L3XVDjiJN2MDDuUS=>	NGHBeHg1QCCq		NW\jUphpeG:2ZX70cJkhcW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCoYYPobY9v	M1;hUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEm4O\|k6Lz5{NEC5PFc6QTxxYU6=
SK-N-AS	M3:wSmZ2dmO2aX;uJGF{e2G7	NHqyZ2kx6oDVOECgcm0>	M{XifVQ5KGh?		M4ftbolv\HWlZYOgZUBld3OnLXTldIVv\GWwdDDjcIVifmGpZTDv[kBk[XOyYYPlJFMh[W6mIGDBVnA>	MlTwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyOUi3PVkoRjJ2MEm4O\|k6RC:jPh?=
SK-N-DZ	NF\LSVJHfW6ldHnvckBCe3OjeR?=	MoriNQKBmzhyIH7N	Mo\6OFghcA>?		MnrnbY5lfWOnczDhJIRwe2VvZHXw[Y5l\W62IHPs[YF3[WenIH;mJINie3Cjc3WgN{BidmRiUFHSVC=>	NV\pUoVKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPVg4QTlpPkK0NFk5Pzl7PD;hQi=>
SK-N-SH	MYXGeY5kfGmxbjDBd5NigQ>?	M4LxclDjiJN2MDDuUS=>	NVTFSpNGPDhiaB?=		MV3pcoR2[2W\|IHGg[I9{\S2mZYDlcoRmdnRiY3zlZZZi\2Vib3[gZ4F{eGG\|ZTCzJIFv\CCSQWLQ	NH7hdnk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEC5PFc6QSd-MkSwPVg4QTl:L3G+
SK-N-BE	MX7GeY5kfGmxbjDBd5NigQ>?	MnHFNQKBmzRyIH7N	MlnMOFghcA>?		MkntbY5lfWOnczDhJIRwe2VvZHXw[Y5l\W62IHPs[YF3[WenIH;mJINie3Cjc3WgN{BidmRiUFHSVC=>	M{PQdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEm4O\|k6Lz5{NEC5PFc6QTxxYU6=
HCC-LM3	MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NX[1fXJDOS1zMECwJI5O	MViyOE81QC95MjDo	MmH6SG1UVw>?	NXXQdoNPcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZo91cCC2aX3lMUBidmRiZH;z[U1l\XCnbnTlcpQhdWGwbnXy	NUfEVY1oRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPVM6PTZpPkK0NFk{QTV4PD;hQi=>
HepG2	MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NED6V5cyNTFyMECgcm0>	NYDGTJh{OjRxNEivO\|IhcA>?	MmP2SG1UVw>?	NYfjNJc3cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZo91cCC2aX3lMUBidmRiZH;z[U1l\XCnbnTlcpQhdWGwbnXy	MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB7M{m1Okc,OjRyOUO5OVY9N2F-
SMMC-7721	MmD5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MoK2NU0yODByIH7N	MUSyOE81QC95MjDo	M3TJO2ROW09?	MXvpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCkb4ToJJRqdWVvIHHu[EBld3OnLXTldIVv\GWwdDDtZY5v\XJ?	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB7M{m1Okc,OjRyOUO5OVY9N2F-
HCC-LM3	M3G3VmFxd3C2b4Ppd{BCe3OjeR?=	MUe1NEBvVQ>?	M{TCO\|Q5KGh?	NGfPW3dFVVOR	M4LFRolv\HWlZYOgZ4VtdCCjcH;weI9{cXNic3nncolncWOjboTsfUBqdiCjIHPhd5Bie2VvZHXw[Y5l\W62IH3hco5meiCkeTDjcIVifmGpZTDv[kBk[XOyYYPld{A{NCB6IHHu[EA6	M2rIUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEmzPVU3Lz5{NEC5N\|k2PjxxYU6=
HepG2	M1LHPGFxd3C2b4Ppd{BCe3OjeR?=	NHz4fm42OCCwTR?=	MnfwOFghcA>?	NGHofoZFVVOR	NV\oPWpkcW6mdXPld{Bk\WyuIHHwc5B1d3OrczDzbYdvcW[rY3HueIx6KGmwIHGgZ4F{eGG\|ZT3k[ZBmdmSnboSgcYFvdmW{IHL5JINt\WG4YXflJI9nKGOjc4Dhd4V{KDNuIEigZY5lKDl?	MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB7M{m1Okc,OjRyOUO5OVY9N2F-
SMMC-7721	NEm2SZdCeG:ydH;zbZMhSXO\|YYm=	NYW0ZlRrPTBibl2=	NFnoW241QCCq	Mn7VSG1UVw>?	M2LKZolv\HWlZYOgZ4VtdCCjcH;weI9{cXNic3nncolncWOjboTsfUBqdiCjIHPhd5Bie2VvZHXw[Y5l\W62IH3hco5meiCkeTDjcIVifmGpZTDv[kBk[XOyYYPld{A{NCB6IHHu[EA6	NFzifVc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEC5N\|k2Pid-MkSwPVM6PTZ:L3G+
HCC-LM3	NGHINGVHfW6ldHnvckBCe3OjeR?=	NUHSUYdKPTBxMUCwJI5O	M2jUN\|I1KGh?	MknsSG1UVw>?	MWPk[YNz\WG\|ZYOgeIhmKGyndnXsd{Bw\iCyLWPURXQ{KGGwZDDwMWFsfMLi	NHvQNZA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEC5N\|k2Pid-MkSwPVM6PTZ:L3G+
HepG2	NELib2tHfW6ldHnvckBCe3OjeR?=	NGn3NI82OC9zMECgcm0>	MVKyOEBp	M13WV2ROW09?	NIjIcFNl\WO{ZXHz[ZMhfGinIHzleoVteyCxZjDwMXNVSVR\|IHHu[EBxNUGtdNMg	MnHhQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyOUO5OVYoRjJ2MEmzPVU3RC:jPh?=
SMMC-7721	Ml7xSpVv[3Srb36gRZN{[Xl?	M1XnOFUxNzFyMDDuUS=>	NXvXXXBpOjRiaB?=	M3\2WGROW09?	MoLQ[IVkemWjc3XzJJRp\SCuZY\lcJMhd2ZicD3TWGFVOyCjbnSgdE1Cc3UEoB?=	M4XGdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEmzPVU3Lz5{NEC5N\|k2PjxxYU6=
HCC-LM3	MnfFSpVv[3Srb36gRZN{[Xl?	MnLzOVAwOTByIH7N	NY\mU5VYOjRiaB?=	MnT5SG1UVw>?	MUDkc5dvemWpdXzheIV{KEKlbD34UEBmgHC{ZYPzbY9v	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB7M{m1Okc,OjRyOUO5OVY9N2F-
HepG2	NEjPdnBHfW6ldHnvckBCe3OjeR?=	MoTNOVAwOTByIH7N	MmfqNlQhcA>?	M4HPSGROW09?	NGrS[mlld3ewcnXneYxifGW\|IFLjcE15VCCneIDy[ZN{cW:w	M{LBfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEmzPVU3Lz5{NEC5N\|k2PjxxYU6=
SMMC-7721	M4rlXWZ2dmO2aX;uJGF{e2G7	MWW1NE8yODBibl2=	NGKwbHczPCCq	NXnrW29MTE2VTx?=	M3fQN4Rwf26{ZXf1cIF1\XNiQnPsMZhNKGW6cILld5Nqd25?	MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB7M{m1Okc,OjRyOUO5OVY9N2F-
FaDu	Mm[4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MXKxNFDjiIWwTR?=	MnvzPE8yOC9zMjDo		Mnew[Il{eGyjeXXkJIEhe2mpbnnmbYNidnRiYX7kJJBzd2yxbnfl[EBIOi:PIHHydoV{fCCjdDC4JIFv\CBzMvMAiYgheG:\|dDDy[Yxm[XOn	M4PUVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEK2OFgzLz5{NECyOlQ5OjxxYU6=
FaDu	NYrJNGZYTnWwY4Tpc44hSXO\|YYm=	M1PCVlExOOLChX7N	NIWyTpYzNzRxOD:xNkBp		NUP2Vow3cW6mdXPl[EBxOjGZYX[xM2NqeDIEoHX4dJJme3Orb36=	NXXWS4ZjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNlY1QDJpPkK0NFI3PDh{PD;hQi=>
PC-3	M{HaPGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M2i1eVAuOTBizszN	NXrLeVhCOjRxNEivO\|IhcA>?		NV34ZoN7cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZo91cCC2aX3lMUBidmRiZH;z[U1l\XCnbnTlcpQhdWGwbnXy	M2nzdVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OUmxNlE3Lz5{M{m5NVIyPjxxYU6=
LNCaP	NHOxU2RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M173c\|AuPSEQvF2=	NEOzN4QzPC92OD:3NkBp		NXyxNGI3cW6qaXLpeJMh[2WubDDndo94fGhiaX6gZo91cCC2aX3lMUBidmRiZH;z[U1l\XCnbnTlcpQhdWGwbnXy	NWDa[oFGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5PVEzOTZpPkKzPVkyOjF4PD;hQi=>
RWPE-1	MnzzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M3zOclAuOjBizszN	MkL1NlQwPDhxN{KgbC=>		Mmn5bY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYn;0bEB1cW2nLTDhcoQh\G:\|ZT3k[ZBmdmSnboSgcYFvdmW{	MoX2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7OUGyNVYoRjJ\|OUmxNlE3RC:jPh?=
Capan-1	NF7mR4dHfW6ldHnvckBCe3OjeR?=	NGrwfYMzPS93MD:xNFAhdk1?	MoPNPE8zPC92ODDo	NVLnRmh4TE2VTx?=	NXnGUYpj\G:5boLl[5Vt[XSnZDDSc44hdVKQQTDhcoQheHKxdHXpckBmgHC{ZYPzbY9vKGGwZDDkc5dve3S{ZXHtJJNq\26jbHnu[y=>	MlfPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7MkK4PFYoRjJ\|OUKyPFg3RC:jPh?=
L3.6pl	NGjtZ\|ZHfW6ldHnvckBCe3OjeR?=	NWDmbFZ3OjVxNUCvNVAxKG6P	NEDoXHQ5NzJ2L{S4JIg>	NHjjRYpFVVOR	NFz1NWZld3ewcnXneYxifGWmIGLvckBuWk6DIHHu[EBxem:2ZXnuJIV5eHKnc4Ppc44h[W6mIHTve45{fHKnYX2gd4lodmGuaX7n	NVz3Z\|IxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5NlI5QDZpPkKzPVIzQDh4PD;hQi=>
CFPAC-1	NGXDcoxHfW6ldHnvckBCe3OjeR?=	NX;meWJjOjVxNUCvNVAxKG6P	MkTwPE8zPC92ODDo	NW\sRphYTE2VTx?=	MW\kc5dvemWpdXzheIVlKFKxbjDtVm5CKGGwZDDwdo91\WmwIHX4dJJme3Orb36gZY5lKGSxd37zeJJm[W1ic3nncoFtcW6p	M3TaRVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OUKyPFg3Lz5{M{myNlg5PjxxYU6=
Capan-1	MmmwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MXmyOU82OC9zMECgcm0>	MmPrOFghcA>?	MkHwSG1UVw>?	NHvDeXhz\WS3Y3XzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz	MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzl{Mki4Okc,OjN7MkK4PFY9N2F-
L3.6pl	MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NYXneYxyOjVxNUCvNVAxKG6P	M3uxT\|Q5KGh?	NYTkenNZTE2VTx?=	M2\xepJm\HWlZYOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>	M1fsUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OUKyPFg3Lz5{M{myNlg5PjxxYU6=
CFPAC-1	Mn3mS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MWCyOU82OC9zMECgcm0>	NH3zSXU1QCCq	NGP0RXBFVVOR	NE[5NnRz\WS3Y3XzJINmdGxiZ4Lve5RpKGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzl{Mki4Okc,OjN7MkK4PFY9N2F-
Capan-1	MUjBdI9xfG:\|aYOgRZN{[Xl?	NVzlenpXOjVxNUCvNVAxKG6P	M3v0OFQ5KGh?	NE\jeWNFVVOR	MkX3bY5lfWOnczDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>	M4nLfVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OUKyPFg3Lz5{M{myNlg5PjxxYU6=
L3.6pl	M3TPbGFxd3C2b4Ppd{BCe3OjeR?=	MnLKNlUwPTBxMUCwJI5O	MYG0PEBp	NFfKPVFFVVOR	MYTpcoR2[2W\|IHPlcIwh\3Kxd4ToJIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy	NFvUPZk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{myNlg5Pid-MkO5NlI5QDZ:L3G+
CFPAC-1	MXfBdI9xfG:\|aYOgRZN{[Xl?	NH7qcmIzPS93MD:xNFAhdk1?	NVHvdnA{PDhiaB?=	NVvGVmVsTE2VTx?=	Mn7DbY5lfWOnczDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>	NYe3V4NRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5NlI5QDZpPkKzPVIzQDh4PD;hQi=>
HN22	Ml:zS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NGP6VIgxNTJyIH7N	MnuxNlQwPDhiaB?=	NH\uSmJFVVOR	NGfJNHBqdmirYnn0d{Bk\WyuII\pZYJqdGm2eTDpckBjd3SqIITpcYUuKGGwZDDkc5NmNSCmZYDlcoRmdnRibXHucoVz	NYjtWXJVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO4O\|czOzVpPkKzPFc4OjN3PD;hQi=>
HSC4	MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M2m1flAuOjBibl2=	NVX5S5dnOjRxNEigbC=>	NIXsT5RFVVOR	NGrUVIpqdmirYnn0d{Bk\WyuII\pZYJqdGm2eTDpckBjd3SqIITpcYUuKGGwZDDkc5NmNSCmZYDlcoRmdnRibXHucoVz	NYP5cYxqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO4O\|czOzVpPkKzPFc4OjN3PD;hQi=>
HN22	NX;NcHk2SXCxcITvd4l{KEG\|c3H5	NX7NVHhiOC1{MDDuUS=>	M{DGdlQ5KGh?	MVHEUXNQ	M4rPbYlv\HWlZYOgZ4VtdCCjcH;weI9{cXN?	NFLJN2M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{i3O\|I{PSd-MkO4O\|czOzV:L3G+
HSC4	M3TQe2Fxd3C2b4Ppd{BCe3OjeR?=	M36zXVAuOjBibl2=	MmTYOFghcA>?	Mkj0SG1UVw>?	NX\zRmRrcW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?=	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzh5N{KzOUc,OjN6N{eyN\|U9N2F-
HN22	NFrReFVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MWiwMVIxKG6P	NFn1c2c1QCCq	Mm\1SG1UVw>?	MWnpcoR2[2W\|IFexJJBp[XOnIHPlcIwh[3mlbHWgZZJz\XO2wrC=	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzh5N{KzOUc,OjN6N{eyN\|U9N2F-
HSC4	NH7K[nVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MVqwMVIxKG6P	MoTMOFghcA>?	NYXxPXB4TE2VTx?=	MX;pcoR2[2W\|IFexJJBp[XOnIHPlcIwh[3mlbHWgZZJz\XO2wrC=	MlnlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN6N{eyN\|UoRjJ\|OEe3NlM2RC:jPh?=
HN22	MXTGeY5kfGmxbjDBd5NigQ>?	NHKw[IIxNTJyIH7N	M{DXdlQ5KGh?	M1TxcmROW09?	MXLzeZBxemW\|c3XzJHNxOSCneIDy[ZN{cW:wwrC=	MnPVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN6N{eyN\|UoRjJ\|OEe3NlM2RC:jPh?=
HSC4	MWHGeY5kfGmxbjDBd5NigQ>?	MoGyNE0zOCCwTR?=	NEjlR5I1QCCq	MnPxSG1UVw>?	M{DnNZN2eHC{ZYPz[ZMhW3BzIHX4dJJme3Orb39CpC=>	MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzh5N{KzOUc,OjN6N{eyN\|U9N2F-
Cal62	MljIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				Mk[5TWM2OD1\|MzFCtUA1KG6P	M4rkdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OEK0NFY1Lz5{M{iyOFA3PDxxYU6=
Hth7	NEfYW3dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=				MoDCTWM2OD1zNTFCtUAzKG6P	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzh{NEC2OEc,OjN6MkSwOlQ9N2F-
Hth83	Mle4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				NUG5OnoxUUN3ME2zOEDDuSB3IH7N	NEnYOJY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{iyOFA3PCd-MkO4NlQxPjR:L3G+
C643	Mmj4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				NX7pT5VvUUN3ME23NUDDuSBzMDDuUS=>	NW\M[WpSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO4NlQxPjRpPkKzPFI1ODZ2PD;hQi=>
SW1736	NHLNfYRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=				MlPrTWM2OD1\|NTFCtUA5KG6P	MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzh{NEC2OEc,OjN6MkSwOlQ9N2F-
T241	M1\YO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7				NG[xVZBKSzVyPU[1JOKyKDdibl2=	MoSwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN6MkSwOlQoRjJ\|OEK0NFY1RC:jPh?=
T351	M1\uO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7				NFzlTpZKSzVyPUWwJOKyKDFyIH7N	NHXiZ4g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{iyOFA3PCd-MkO4NlQxPjR:L3G+
BHP2-7	NUe0eZdST3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=				M3zOXGlEPTB;M{egxtEhPiCwTR?=	M2r0WlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OEK0NFY1Lz5{M{iyOFA3PDxxYU6=
T238	MnLDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				MWTJR\|UxRTFuNUCwJOKyKDJyMDDuUS=>	MnraQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN6MkSwOlQoRjJ\|OEK0NFY1RC:jPh?=
HCT8	MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		MmXkO\|IhcA>?	NEPyOYRFVVOR	NWOxdZZ2UUN3ME2xNk466oDLwsJihKkyNjlibl2=	M4P2U\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|Mkm5N\|g5Lz5{M{K5PVM5QDxxYU6=
H630	MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		NETyOI44OiCq	NUjGdYdJTE2VTx?=	NWjoPFJ{UUN3ME2xNk416oDLwsJihKk{NjFibl2=	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzJ7OUO4PEc,OjN{OUmzPFg9N2F-
cH630 5-FU-res	MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		NYGydm13PzJiaB?=	NVXJcYgzTE2VTx?=	NFvDeJBKSzVyPUG1MlXjiIoEsfMAjVEvOiCwTR?=	MlzMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN{OUmzPFgoRjJ\|Mkm5N\|g5RC:jPh?=
HCT116	MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		MXG3NkBp	MW\EUXNQ	MXvJR\|UxRTFyLkhihKnDueLCiUKuNkBvVQ>?	NIfSOJQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{K5PVM5QCd-MkOyPVk{QDh:L3G+
HCT116 p53−/−	MnSzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		NG\ZN\|I4OiCq	M1i0dWROW09?	MkHCTWM2OD16LkdihKnDueLCiUGuO{BvVQ>?	NHf5TmY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{K5PVM5QCd-MkOyPVk{QDh:L3G+
dHCT116 p21−/−	MVnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		M1vwc\|czKGh?	NGrlNmVFVVOR	M1X6TGlEPTB;NT655qCKyrIkgJmxMlMhdk1?	NYiyOItZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOyPVk{QDhpPkKzNlk6Ozh6PD;hQi=>
HT29	NHHkdoJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		MnfqO\|IhcA>?	NH7OV2dFVVOR	NWTLfFY{UUN3ME2xOk4{6oDLwsJihKkzNjNibl2=	NFTBRnQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{K5PVM5QCd-MkOyPVk{QDh:L3G+
LoVo	MoTES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		M3:2NFczKGh?	MXfEUXNQ	NFfJdZBKSzVyPUWuNgKBkcLz4pEJNE43KG6P	NHGyV449[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{K5PVM5QCd-MkOyPVk{QDh:L3G+
RKO	NUX1cphXT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		NIfnd204OiCq	MUTEUXNQ	MVzJR\|UxRTdwOfMAjeKy6oDLMj6yJI5O	MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzJ7OUO4PEc,OjN{OUmzPFg9N2F-
SW480	NHXjOWVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		MU[3NkBp	NVflXpJnTE2VTx?=	NXv1dY9SUUN3ME2xO{426oDLwsJihKkxNjhibl2=	MlP5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN{OUmzPFgoRjJ\|Mkm5N\|g5RC:jPh?=
eSW620	NWT0d\|R1T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		MmjaO\|IhcA>?	NWC1e5RpTE2VTx?=	NGLTU3dKSzVyPUmuNgKBkcLz4pEJNk4yKG6P	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzJ7OUO4PEc,OjN{OUmzPFg9N2F-
S2	NGqxXZFHfW6ldHnvckBie3OjeR?=				NU\OU2pLUW6qaXLpeIlwdiCxZjDQcIF{dW:maYXtJIZidGOrcHHyeY0hUESDQ{Gg[ZhxemW\|c3XkJIlvKES{b4PvdIhqdGFibXXsZY5w\2G\|dHXyJHMzKGOnbHzzMEBKSzVyIE2gNE4xODF6IN88UU4>	NELiVoI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUOxO\|Q2OCd-MUmzNVc1PTB:L3G+
COLO205	NXTiW2dGSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		NWrkdXBiQTZiaILz		NWDYOo5MSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDDU2xQOjB3IHPlcIx{KGGodHXyJFk3KGi{czDifUBk\WyudHn0[ZIhQTZiYYPzZZktKEmFNUCgQUAxNjBzODFOwG0v	M13nZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzNkO0OFMxLz5{MU[zOFQ{ODxxYU6=
PC3	NF7qT4tCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		MoPjPVYhcHK\|		NFzyPVdCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGDDN{Bk\WyuczDh[pRmeiB7NjDodpMh[nliY3XscJRqfGW{IEm2JIF{e2G7LDDJR\|UxKD1iMD6wNlQh\|ryPLh?=	NX;ZT3N[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG2N\|Q1OzBpPkKxOlM1PDNyPD;hQi=>
A2780	NXn5VJBtSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		M1;sbFk3KGi{cx?=		NUHQbnQ2SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDBNlc5OCClZXzsd{Bi\nSncjC5OkBpenNiYomgZ4VtdHSrdHXyJFk3KGG\|c3H5MEBKSzVyIE2gNE4xOzVizszNMi=>	NXq5Rm8xRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG2N\|Q1OzBpPkKxOlM1PDNyPD;hQi=>
HCT116	M2\PRWFvfGmycn;sbYZmemG2aY\lJIF{e2G7		MnewPVYhcHK\|		M3fTcmFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFPUNVE3KGOnbHzzJIFnfGW{IEm2JIhzeyCkeTDj[YxtfGm2ZYKgPVYh[XO\|YYmsJGlEPTBiPTCwMlA1QCEQvF2u	MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTZ\|NESzNEc,OjF4M{S0N\|A9N2F-
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Raji	MkPMR5l1d3SxeHnjbZR6KGG\|c3H5		MlftNlQhcHK\|		Mnj1R5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gVoFrcSClZXzsd{Bie3Onc4Pl[EBieyCpcn;3eIghcW6qaXLpeIlwdiCjZoTldkAzPCCqcoOgZpkhVVSWIHHzd4F6	NEXJS\|M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{G4OlY4Pid-MkexPFY3PzZ:L3G+
Ramos	NUfTZZJXS3m2b4TvfIlkcXS7IHHzd4F6		NYPkVINnOjRiaILz		NWTSNVdGS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hWmGvb4OgZ4VtdHNiYYPz[ZN{\WRiYYOg[5Jwf3SqIHnubIljcXSrb36gZYZ1\XJiMkSgbJJ{KGK7IF3UWEBie3OjeR?=	MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzF6Nk[3Okc,OjdzOE[2O\|Y9N2F-
U266	NF3VNYNEgXSxdH;4bYNqfHliYYPzZZk>		NXLye5d5OjRiaILz		NHXacWVEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBWOjZ4IHPlcIx{KGG\|c3Xzd4VlKGG\|IHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDJ2IHjyd{BjgSCPVGSgZZN{[Xl?	MoG5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjdzOE[2O\|YoRjJ5MUi2Olc3RC:jPh?=
RPMI8226	MkD6R5l1d3SxeHnjbZR6KGG\|c3H5		MX[yOEBpenN?		NH;TdYxEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBTWE2LOEKyOkBk\WyuczDhd5Nme3OnZDDhd{Boem:5dHigbY5pcWKrdHnvckBi\nSncjCyOEBpenNiYomgUXRVKGG\|c3H5	MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPzF6Nk[3Okc,OjdzOE[2O\|Y9N2F-
HBL1	MVPDfZRwfG:6aXPpeJkh[XO\|YYm=		MVeyOEBpenN?		M3rrNWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJGhDVDFiY3XscJMh[XO\|ZYPz[YQh[XNiZ4Lve5RpKGmwaHnibZRqd25iYX\0[ZIhOjRiaILzJIJ6KE2WVDDhd5NigQ>?	MoPxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjdzOE[2O\|YoRjJ5MUi2Olc3RC:jPh?=
MM1S	Mof3R5l1d3SxeHnjbZR6KGG\|c3H5		NFv6WnozPCCqcoO=		MkPUR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUW0yWyClZXzsd{Bie3Onc4Pl[EBieyCpcn;3eIghcW6qaXLpeIlwdiCjZoTldkAzPCCqcoOgZpkhVVSWIHHzd4F6	MnPSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjdzOE[2O\|YoRjJ5MUi2Olc3RC:jPh?=
OCI-LY1	NHzKOIFEgXSxdH;4bYNqfHliYYPzZZk>		MVWyOEBpenN?		NHHn[2lEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBQS0lvTGmxJINmdGy\|IHHzd4V{e2WmIHHzJIdzd3e2aDDpcohq[mm2aX;uJIFnfGW{IEK0JIhzeyCkeTDNWHQh[XO\|YYm=	NYrI[oFwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkexPFY3PzZpPkK3NVg3Pjd4PD;hQi=>
SUDHL4	NWnhN3pFS3m2b4TvfIlkcXS7IHHzd4F6		NYPE[mxrOjRiaILz		NFrVWo5EgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBUXUSKTESgZ4VtdHNiYYPz[ZN{\WRiYYOg[5Jwf3SqIHnubIljcXSrb36gZYZ1\XJiMkSgbJJ{KGK7IF3UWEBie3OjeR?=	M2TlNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5MUi2Olc3Lz5{N{G4OlY4PjxxYU6=
MV4-11	NEjOSGtHfW6ldHnvckBie3OjeR?=	MVu1NEBvVQ>?	MUGyOEBpenN?		MX\JcoR2[3Srb36gc4YhUESDQ{[g[IVoemGmYYTpc44hcW5iaIXtZY4hVVZ2LUGxJINmdGy\|IHH0JFUxKG6PIHHmeIVzKDJ2IHjyd{BjgSCZZYP0[ZJvKGKub4SgcYV1cG:m	MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTV6OUS0NUc,Ojl3OEm0OFE9N2F-
MV4-11	NFX2NIRHfW6ldHnvckBie3OjeR?=	NX3aS4Z6PTBibl2=	MmPxNkB1dyB{NDDodpM>		NF\SWoxKdmirYnn0bY9vKG:oIFjERWM3KGmwIHj1cYFvKE2YND2xNUBk\WyuczDhd5Nme3OnZDDhd{BqdmS3Y4Tpc44hd2ZiYXzwbIEufHWkdXzpckBpgXCncnHj[ZR6dGG2aX;uJIF1KDVyIH7NJIFnfGW{IEKgeI8hOjRiaILzJIJ6KFenc4Tldo4h[myxdDDt[ZRpd2R?	Mn2wQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl3OEm0OFEoRjJ7NUi5OFQyRC:jPh?=
MV4-11	M1;RbGNmdGxiY4njcIUh[XK{ZYP0JIF{e2G7	NXjxfIo3OzBidH:gOVAhdk1?	MlXCNlQhcHK\|		NFTKeWhE\WyuIHP5Z4xmKGG{cnXzeEBqdiCqdX3hckBOXjRvMUGgZ4VtdHNiYYPz[ZN{\WRiYYOgZYNkfW23bHH0bY9vKGG2IIP1Zk1IOSCyaHHz[UBifCB\|MDD0c{A2OCCwTTDh[pRmeiB{NDDodpMh[nlicILvdIllcXWvIHnv[Ill\SC\|dHHpcolv\y2kYYPl[EBndG:5IHP5eI9u\XS{aXOgcYV1cG:m	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTV6OUS0NUc,Ojl3OEm0OFE9N2F-
MV4-11	MU\BdI9xfG:\|aYOgZZN{[Xl?	MV6zNEBvVQ>?	M1TrNFI1KHSxIES4JIhzew>?		MYrJcoR2[3Srb36gc4Yh[XCxcITvd4l{KGmwIHj1cYFvKE2YND2xNUBk\WyuczDheEA{OCCwTTDh[pRmeiB{NDD0c{A1QCCqcoOgZpkhSW6wZYjpckBXNVCLIIP0ZYlvcW6pIHLhd4VlKG[ub4egZ5l1d22ndIL5	MnzZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl5M{i5OVMoRjJ7N{O4PVU{RC:jPh?=

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	DNMT1 / EZH2; PubMed: 19279403 Cancer Biol Ther Western blot of DNMT1 and EZH2 in K562 and LAMA84 following 24 hours treatment with the indicated doses of panobinostat (PS). The levels of β-actin served as the loading control. caspase-8 / cleaved caspase-8 / Sp1; PubMed: 27738323 Oncotarget The indicated MM cell lines were cultured for 24 hours in the absence or presence of panobinostat at the indicated concentrations. Then, the protein levels of caspase-8, cleaved caspase 8 and Sp1 were analyzed by Western blotting. c-Myc / IRF4; PubMed: 27738323 Oncotarget RPMI8226 cells were cultured for 24 hours in the absence or presence of panobinostat at the indicated concentrations. Then, the protein levels of cMyc and IRF4 were analyzed by Western blotting. Ac-H3 / cleaved caspase-3 / CCND1 / ID1 / ID2 / ID3 / ID4 / Synaptophysin / NeuroD1; PubMed: 28915627 Oncotarget Immunoblotting of whole cell lysates prepared from MB cells treated with panobinostat. The representative western blot result shows panobinostat clearly regulated acetyl-Histone H3 (Ac-H3), cleaved caspase-3, CCND1, IDs, synaptophysin and NeuroD1. RAD51 / BRCA1 / CHK1 / RPL13a; PubMed: 24244429 PLoS One CTS, OCI-AML3 or U937 AML cells were treated with variable concentrations of panobinostat for 48 h. Whole cell lysates were subjected to Western blotting to measure protein levels for BRCA1, CHK1, and RAD51 in the cells. H3K9AC / H3K18AC / H3K56AC / H3 / H4K8AC / H4K16AC / H4 / p21 / p27 / cleaved PARP; PubMed: 31071955 Int J Mol Sci Immunoblot analyses of histone acetylation (H3K9AC, H3K18AC, H3K56AC, H4K8AC and H4K16AC), cell cycle arrest (p27 and p27) and apoptotic-related protein (C-Caspase 3 and C-PARP) expression following various panobinostat treatments for 6 h and 24 h on K562 cells. H3, H4 and GAPDH immunoblots served as internal controls.	19279403 27738323 28915627 24244429 31071955
Immunofluorescence	Synaptophysin / NACM; PubMed: 28915627 Oncotarget Panobinostat treated cells are positive for (B) synaptophysin (red) and (C) NCAM (red). Scale bars, 50 μm. α-tubulin / Acetyl-α-tubulin; PubMed: 29983882 Oncotarget CLBL-1 cells were treated with 10 nM of panobinostat for 24 h and then microtubules were visualized by immunofluorescence labeling using antibodies against tubulin and acetylated tubulin (ac-tubulin) using the appropriate excitation and emission filters as described in the material and methods section. Representative microphotographs with tubulin and ac-tubulin labeling (green) and DAPI stained-nuclei (blue) at 100× magnification are shown. Scale bar, 5 μm. BiP; PubMed: 23544167 Transl Oncol Immunofluorescence analysis of BiP after 24 and 48 hours of treatment in HepG2 (upper panel) and Hep3B (lower panel) cells with 0.1 µM panobinostat and 10 nM thapsigargin, showing an increase and a different protein distribution in panobinostat-treated cells, comparable to 10 nM thapsigargin effect, used as a positive control. Immunofluorescence analysis has been performed under identical settings. Nuclei were stained with Hoechst 33342. Magnification is x630, and scale bar represents 10 µm. ATF4; PubMed: 23544167 Transl Oncol HepG2 (left panel) and Hep3B (right panel) cells were treated for 24 and 48 hours with 0.1 µM panobinostat and the immunofluorescence results show an increase of ATF4 and its nuclear localization in both cell lines. Immunofluorescence analysis has been performed under identical settings. Nuclei were stained with Hoechst 33342. Magnification is x630, and scale bar represents 10 µm. IRE1α / S724-IRE1α; PubMed: 23544167 Transl Oncol Analysis of IRE1α/XBP1 involvement. Immunofluorescence results of IRE1α and its phosphorylated form in HepG2 (A) and Hep3B (B) cell lines after 24 and 48 hours of treatment with 0.1 µM panobinostat. The results indicate that panobinostat induces an increase of both the total and the phosphorylated form of IRE1α and a spotted distribution of this protein (enlargement showed for phospho-IRE1α, B). Immunofluorescence analysis has been performed under identical settings. Nuclei were stained with Hoechst 33342. Magnification is x630, and scale bar represents 10 µm.	28915627 29983882 23544167
Growth inhibition assay	Cell viability; PubMed: 27738323 Oncotarget The indicated MM cell lines were cultured in triplicate in the absence or presence of panobinostat at the indicated concentrations. After culturing for 48 hours, cell viability was measured by a WST-8 cell proliferation assay. Results were expressed as the mean +/− SD.	27738323

In vivo

In lung cancer and mesothelioma animal models, LBH589 markedly decreases tumor growth by 62%. LBH589 is equally effective in immunocompetent and severe combined immunodeficien-cymice, suggesting that the inhibition of tumor growth by LBH589 is not due to direct immunologic effects. Daily LBH589, given i.p. at 20 mg/kg for 5 days per week, leading to an average decrease in growth of 70%. Compared with the corresponding control tumors, LBH589 leads to a 53% decrease for H526-derived tumors, an 81% decrease for BK-T-derived tumors, a 76% decrease for RG-1- derived tumors, and a 70% decrease for H69-derived tumors. In contrast to the lack of tumor regression notes in NSCLC and Meso-derived xenografted tumors that are treated under identical conditions and doses, LBH589 results in dramatic tumor regression in SCLC-derived tumors and RG-1-derived tumor. ^[2]

Protocol

Cell Research:^[1]

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Cell lines: MOLT-4 cell lines and Reh (pre-B cells)
Concentrations: 50 nM
Incubation Time: 48 hours
Method: Untreated and LBH589-treated cells [human Ph- acute lymphoblastic leukemia MOLT-4 (T cells) and Reh (pre-B cells)] are stained with annexin V and propidium iodide using annexin V-FITC apoptosis detection kit I. The percentage of apoptotic and nonviable cells is determined by flow cytometry. At least 5 × 10⁴ cells are collected with a CyAn ADP Violet cytometer. Percentage apoptosis is calculated considering all the annexin V-positive plus the annexin V/PI-positive cells; percentage loss of cell viability is calculated considering all the annexin V-positive plus the PI-positive and the annexinV/PI-positive cells.
(Only for Reference)

Animal Research:^[2]

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Animal Models: Severe combined immunodeficiency (SCID) mice with M30 (10⁷ cells) or A549 (5 × 10⁶ cells), H69 (2.5 × 10⁶ cells), BK-T (6.5 × 10⁶), H526 (10 × 10⁶), and RG1 (10 × 10⁶) cells
Dosages: 10 mg/kg, 20 mg/kg
Administration: Administered via i.p. injection
(Only for Reference)

References

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Solubility (25°C)

In vitro	DMSO	69 mg/mL (197.46 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 2% DMSO+48% PEG 300+2% Tween 80+ddH2O For best results, use promptly after mixing.	5mg/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 Panobinostat (LBH589) SDF

Molecular Weight	349.43
Formula	C₂₁H₂₃N₃O₂
CAS No.	404950-80-7
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	NVP-LBH589
Smiles	CC1=C(C2=CC=CC=C2N1)CCNCC3=CC=C(C=C3)C=CC(=O)NO

In vivo Formulation Calculator (Clear solution)

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Working concentration： mg/ml；

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.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

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Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2021-09-06)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04341311	Active not recruiting	Drug: Marizomib\|Drug: Panobinostat	Diffuse Intrinsic Pontine Glioma\|Pediatric Brainstem Glioma\|Pediatric Brainstem Gliosarcoma Recurrent\|Pediatric Cancer\|Pediatric Brain Tumor\|Diffuse Glioma	Dana-Farber Cancer Institute\|Celgene\|Secura Bio Inc.	August 10 2020	Phase 1
NCT03632317	Withdrawn	Drug: Panobinostat\|Drug: Everolimus	Glioma\|Diffuse Intrinsic Pontine Glioma	University of Michigan Rogel Cancer Center	October 2019	Phase 2
NCT03982134	Withdrawn	Drug: PDR001\|Drug: Panobinostat	Melanoma\|Non Small Cell Lung Cancer	Muhammad Furqan\|Novartis Pharmaceuticals\|University of Iowa	September 2019	Phase 1
NCT04326764	Recruiting	Drug: Panobinostat	Acute Myeloid Leukaemia (AML)\|Myelodysplastic Syndromes (MDS)	Goethe University\|Jan J. Cornelissen (HOVON-SAKK)\|Sebastian Giebel (PALG)	July 24 2018	Phase 3
NCT03515915	Unknown status	--	Patients With Recurrent or Refractory Multiple Myeloma	University Hospital Montpellier\|Poitiers University Hospital	April 23 2018	--

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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Frequently Asked Questions

Question 1:
How to reconstitute the compound for in vivo mice study?
Answer:
We recommend the vehicle is 2 % DMSO, 2 % Tween 80, 48%PEG300, 48% water. The compound is first dissolved in DMSO, then add Tween, PEG300, water in sequence.

HDAC Signaling Pathway Map

HDAC Inhibitors with Unique Features

Selective HDAC Inhibitor

Rocilinostat (ACY-1215) : HDAC5-selective, IC50=5 nM.
Most Potent HDAC Inhibitor

Quisinostat (JNJ-26481585) : HDAC1, IC50=0.11 nM; HDAC2, IC50=0.33 nM.
FDA-approved HDAC Inhibitor

Vorinostat (SAHA, MK0683) : Approved by FDA for cutaneous T cell lymphoma.
Newest HDAC Inhibitor

RG2833 (RGFP109) ^New : Brain-penetrant HDAC inhibitor with IC50 of 60 nM and 50 nM for HDAC1 and HDAC3, respectively.

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Vorinostat (SAHA)

Vorinostat (suberoylanilide hydroxamic acid, SAHA, MK0683) is an HDAC inhibitor with IC50 of ~10 nM in a cell-free assay. Vorinostat abrogates productive HPV-18 DNA amplification.
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Entinostat (MS-275, SNDX-275) strongly inhibits HDAC1 and HDAC3 with IC50 of 0.51 μM and 1.7 μM in cell-free assays, compared with HDACs 4, 6, 8, and 10. Entinostat induces autophagy and apoptosis. Phase 3.
Trichostatin A (TSA)

Trichostatin A (TSA) is an HDAC inhibitor with IC50 of ~1.8 nM in cell-free assays.
Romidepsin (FK228, Depsipeptide)

Romidepsin (FK228, Depsipeptide, FR 901228, NSC 630176) is a potent HDAC1 and HDAC2 inhibitor with IC50 of 36 nM and 47 nM in cell-free assays, respectively. Romidepsin (FK228/depsipeptide) controls growth and induces apoptosis in neuroblastoma tumor cells.

Features:More effective than other classical HDAC inhibitors such as TSA, TPX, and butyrate.
Tubastatin A

Tubastatin A is a potent and selective HDAC6 inhibitor with IC50 of 15 nM in a cell-free assay. It is selective against all the other isozymes (1000-fold) except HDAC8 (57-fold). Tubastatin A promotes autophagy and increases apoptosis.
Mocetinostat (MGCD0103)

Mocetinostat (MGCD0103, MG0103) is a potent HDAC inhibitor with most potency for HDAC1 with IC50 of 0.15 μM in a cell-free assay, 2- to 10- fold selectivity against HDAC2, 3, and 11, and no activity to HDAC4, 5, 6, 7, and 8. Mocetinostat (MGCD0103) induces apoptosis and autophagy. Phase 2.

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Panobinostat (LBH589)