Panobinostat (LBH589)

Name: Panobinostat (LBH589)
Brand: Selleck Chemicals
SKU: S1030
Rating: 5 (289 reviews)

For research use only.

Catalog No.S1030 Synonyms: NVP-LBH589

289 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 289 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 Cell, 2016, 29(3):311-323

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Nat Med, 2015, 10.1038/nm.3855

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Cell, 2014, 20;159(5):1110-1125.

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

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Cancer Biol Ther, 2021, 22(1):66-78

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

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PLoS One, 2021, 16(1):e0237554

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Blood, 2020, 10.1182/blood.2019004332

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Nat Commun, 2020, 11(1):6425

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Nat Commun, 2020, 11(1):583

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Sci Immunol, 2020, 5(50):eabb5168

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Int J Cancer, 2020, 10.1002/ijc.33046

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

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Mol Cancer Res, 2020, 10.1158/1541-7786.MCR-19-0669

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Front Oncol, 2020, 10:296

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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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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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Cancers (Basel), 2019, 11(10)

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PLoS Pathog, 2019, 15(8):e1007991

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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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Front Immunol, 2019, 9:3162

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

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Mol Cancer Ther, 2019, 18(1):185-195

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Mol Cancer Ther, 2019, 18(8):1439-1450

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Oncologist, 2019, 24(8):e740-e748

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

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J Biomed Nanotechnol, 2019, 15(5):979-992

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Epigenetics, 2019, 10.1080/15592294.2019.1656156

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

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J Nanobiotechnology, 2019, 17(1):69

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Nat Commun, 2018, 9(1):4866

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Int J Cancer, 2018, 143(6):1388-1401

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Oncogene, 2018, 37(50):6414-6424

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

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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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Int J Radiat Oncol Biol Phys, 2018, 100(1):174-187

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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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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(5):2191-2208

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

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

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Methods Mol Biol, 2017, 1510:127-148

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

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Nucleic Acids Res, 2016, 45(3):1159-1176

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EMBO Mol Med, 2016, 8(2):117-38

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

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

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Nat Commun, 2015, 3;6:10091

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Cancer Res, 2015,

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Mol Oncol, 2015, 9(7):1447-1457

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Mol Pharm, 2015, 12(7):2469-76

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Antimicrob Agents Chemother, 2015, 59(7):3984-94

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Sci Rep, 2015, 5:16445

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Cancer Biol Ther, 2015, 16(12):1784-93

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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	NXKxN2lRT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NV\5eopVOC1zMDFOwG0>	MUOwMVQh\A>?		MlrObY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYn;0bEB1cW2nLTDhcoQh\G:\|ZT3k[ZBmdmSnboSgcYFvdmW{	MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjdyMke4OEc,OjZ5MEK3PFQ9N2F-
HepG2	MojRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NGTLb3UxNTFyIN88US=>	MVSwMVQh\A>?		NYDIWohvcW6qaXLpeJMh[2WubDDndo94fGhiaX6gZo91cCC2aX3lMUBidmRiZH;z[U1l\XCnbnTlcpQhdWGwbnXy	Mnz4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ5MEK3PFQoRjJ4N{CyO\|g1RC:jPh?=
HT29	MoP4SpVv[3Srb36gRZN{[Xl?	NUjOS\|d5PTEEoH7N	NFrUNWMzPC15MjDo		NUXzdVNtcW6mdXPl[EBi[3SrdnH0bY9vKG:oIHPhd5Bie2ViMzDh[pRmeiB2ONMgbOKh	NHj4epU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkewNlc5PCd-Mk[3NFI4QDR:L3G+
HepG2	MmPxSpVv[3Srb36gRZN{[Xl?	NYXnUItPPTEEoH7N	MWGyOE04OiCq		NHG5c4VqdmS3Y3XkJIFkfGm4YYTpc44hd2ZiY3HzdIF{\SB\|IHHmeIVzKDJ2wrDoxsA>	MnPaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ5MEK3PFQoRjJ4N{CyO\|g1RC:jPh?=
HCC827	M{DTcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NWPpcXlbPS95LkWvNVAhdk1?	MljjO\|LDqGh?	M{DxcGROW09?	NFzjdYNmdmijbnPld{B1cGViYX70bZBzd2yrZnXyZZRqfmViZX\m[YN1KG:oIHXycI91cW6rYh?=	NGf3VY89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{Nk[3OVQ5PCd-Mk[2O\|U1QDR:L3G+
A549	MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NHjRVVAyOC9zNT:yNEBvVQ>?	MnPrO\|LDqGh?	M1XxTmROW09?	M3TjN4VvcGGwY3XzJJRp\SCjboTpdJJwdGmoZYLheIl3\SCnZn\lZ5Qhd2ZiZYLsc5Rqdmmk	M3L1S\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4Nke1OFg1Lz5{Nk[3OVQ5PDxxYU6=
NCI-H460	NEDDXZdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MUGxNE8zOC9\|MDDuUS=>	NV[5SYUyPzMEoHi=	MkDHSG1UVw>?	Mo\o[Y5p[W6lZYOgeIhmKGGwdHnwdo9tcW[ncnH0bZZmKGWoZnXjeEBw\iCncnzveIlvcWJ?	M4rETVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4Nke1OFg1Lz5{Nk[3OVQ5PDxxYU6=
J89GFP	NFzWVIdIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NEXjNW9FVVORwrC=	Mo[2SWM2OD12OT64OUDDuSBzMj62OUBvVQ>?	Mn\QQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ3NkO1OlgoRjJ4NU[zOVY5RC:jPh?=
THP89GFP	NIXWUpJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			M4jXOWROW00EoB?=	NFfmeHJGSzVyPUG5MlM1KMLzIE[uOFMhdk1?	NXnCTZFURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[1OlM2PjhpPkK2OVY{PTZ6PD;hQi=>
SK-NEP-1	MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MmfvNE4xOeLCk{GwMlAh\|ryP	MnXvNlQhcA>?	NHu1UmFFVVORwrC=	MVfJR\|UxRTd4LkO0JI5O	NF7lZYY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkG3OlIyQSd-Mk[xO\|YzOTl:L3G+
G401	NX\kd3lqT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MmDjNE4xOeLCk{GwMlAh\|ryP	MVSyOEBp	NIPSUZFFVVORwrC=	NVzaNZY1UUN3ME2xOFMvODJibl2=	MkT4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzN{[yNVkoRjJ4MUe2NlE6RC:jPh?=
SK-NEP-1	NXrrbY92S2WubDDWbYFjcWyrdImgRZN{[Xl?	M3\mUVUxKG6P	NELneGwy6oDVNDDk	MoK5SG1UV8Li	MmfudoVlfWOnczDj[YxtKHO3co\peoFtKGmwIHGgeIlu\SCmZYDlcoRmdnRibXHucoVz	Mn;4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzN{[yNVkoRjJ4MUe2NlE6RC:jPh?=
G401	NFjlSoxE\WyuIG\pZYJqdGm2eTDBd5NigQ>?	MYm1NEBvVQ>?	M2juSVHjiJN2IHS=	MkXXSG1UV8Li	MUny[YR2[2W\|IHPlcIwhe3W{dnn2ZYwhcW5iYTD0bY1mKGSncHXu[IVvfCCvYX7u[ZI>	M4XGTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUe2NlE6Lz5{NkG3OlIyQTxxYU6=
SK-NEP-1	MnLoRZBweHSxc3nzJGF{e2G7	NV7kSZlQPTBxMUCwJI5O	Mnr6NlQhcA>?	M{fuUWROW00EoB?=	NIC4OWFqdmS3Y3XzJINmdGxiYYDvdJRwe2m\|IHnuJIEh\G:\|ZT3k[ZBmdmSnboSgcYFvdmW{	M13Q[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUe2NlE6Lz5{NkG3OlIyQTxxYU6=
G401	NVvOTpM3SXCxcITvd4l{KEG\|c3H5	MVi1NE8yODBibl2=	M4jJTFI1KGh?	MYXEUXNQyqB?	M1vOW4lv\HWlZYOgZ4VtdCCjcH;weI9{cXNiaX6gZUBld3OnLXTldIVv\GWwdDDtZY5v\XJ?	NVHWS4lSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xO\|YzOTlpPkK2NVc3OjF7PD;hQi=>
SK-NEP-1	M1[4eWZ2dmO2aX;uJGF{e2G7	M4SxfVUxNzFyMDDuUS=>	MWqyOEBp	MoPvSG1UV8Li	NV3aOIt2e2ixd4OgeIhmKGmwZIXjeIlwdiCxZjDEUmEh\nKjZ33lcpRifGmxbh?=	NWfuU5NmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xO\|YzOTlpPkK2NVc3OjF7PD;hQi=>
G401	Ml3RSpVv[3Srb36gRZN{[Xl?	Ml\zOVAwOTByIH7N	M2H4WlI1KGh?	NIrqNndFVVORwrC=	MnLVd4hwf3NidHjlJIlv\HWldHnvckBw\iCGTlGg[pJi\22nboTheIlwdg>?	M{fZWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUe2NlE6Lz5{NkG3OlIyQTxxYU6=
SK-NEP-1	M325SWZ2dmO2aX;uJGF{e2G7	NVTjT4JPPTBxMUCwJI5O	MoD3NlQhcA>?	M2jKPWROW00EoB?=	MoG2bY5lfWOnczDj[YxtKGO7Y3zlJIRqe2:{ZHXyxsA>	MoLLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzN{[yNVkoRjJ4MUe2NlE6RC:jPh?=
G401	M3;1RWZ2dmO2aX;uJGF{e2G7	MmT5OVAwOTByIH7N	MmPhNlQhcA>?	NWL1WYNUTE2VT9Mg	MnPqbY5lfWOnczDj[YxtKGO7Y3zlJIRqe2:{ZHXyxsA>	M17oPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUe2NlE6Lz5{NkG3OlIyQTxxYU6=
RPMI 8226	NFmyb2VE\WyuIGP1dpZqfmGuIFHzd4F6	M2K0elIwPC94IH7N	MkXaOFjjiImq		M1ftUYlv\HWlZYOgZUB{cWewaX\pZ4FvfCCmZXPy[YF{\SCrbjD0bIUh[2WubDDndo94fGh?	Mlz0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyMECyPVIoRjJ4MECwNlkzRC:jPh?=
OPM2	MkfwR4VtdCCVdYL2bZZidCCDc4PhfS=>	NYL4TGVnOi92L{[gcm0>	NGfXblU1QOLCiXi=		MY\pcoR2[2W\|IHGgd4lodmmoaXPhcpQh\GWlcnXhd4UhcW5idHjlJINmdGxiZ4Lve5Rp	M2HWdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MECwNlkzLz5{NkCwNFI6OjxxYU6=
U266	Ml7sR4VtdCCVdYL2bZZidCCDc4PhfS=>	MlTwNk81NzZibl2=	Ml;3OFjjiImq		M17tUIlv\HWlZYOgZUB{cWewaX\pZ4FvfCCmZXPy[YF{\SCrbjD0bIUh[2WubDDndo94fGh?	M17XdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MECwNlkzLz5{NkCwNFI6OjxxYU6=
H929	NGLTPXdE\WyuIGP1dpZqfmGuIFHzd4F6	MWCyM\|QwPiCwTR?=	NVracoRDPDkkgJno		Mo[xbY5lfWOnczDhJJNq\26rZnnjZY51KGSnY4LlZZNmKGmwIITo[UBk\WyuIHfyc5d1cA>?	M{jXZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MECwNlkzLz5{NkCwNFI6OjxxYU6=
RPMI 8226	NImxSpVCeG:ydH;zbZMhSXO\|YYm=	MXq05qCKdk1?	Mof2NlQwPDhiaB?=		NGTpbGFqdmS3Y3XzJINmdGxiYYDvdJRwe2m\|IHnuJIEhfGmvZT3k[ZBmdmSnboSgcYFvdmW{	Mmq1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyMECyPVIoRjJ4MECwNlkzRC:jPh?=
HCC827	NHHvTXBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MnfWNVAhdk1?	M4jWUVQ5KGh?	Mly1SG1UVw>?	NWDjeWk5\W6qYX7j[ZMh[2m\|cHzheIlvKHOnboPpeIl3cXS7wrC=	NY\XXZZ1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW5OFQ3OTdpPkK1PVQ1PjF5PD;hQi=>
NCI-H23	NYPVZZU4T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	M2W4VlExKG6P	NV\0SlRvPDhiaB?=	MlPvSG1UVw>?	NV\xdGdE\W6qYX7j[ZMh[2m\|cHzheIlvKHOnboPpeIl3cXS7wrC=	MonPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV7NES2NVcoRjJ3OUS0OlE4RC:jPh?=
AML3	MkTxSpVv[3Srb36gRZN{[Xl?	MVqwMVEh\|ryP	NEfuUmwzPMLiaB?=		NVXZS3oxcW6mdXPld{BFVkFiZoLh[41mdnSjdHnvcuKhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>	M1jlSlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkGyPVQyLz5{NU[xNlk1OTxxYU6=
ML-1	NYHZeHFQTnWwY4Tpc44hSXO\|YYm=	NHjO[pkxNTFizszN	NEXFbZMzPMLiaB?=		MmnwbY5lfWOnczDEUmEh\nKjZ33lcpRifGmxbtMgbY4h[SCmb4PlMYRmeGWwZHXueEBu[W6wZYK=	M3zLWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkGyPVQyLz5{NU[xNlk1OTxxYU6=
RPMI-8226vr10	NX;4TotiTnWwY4Tpc44hSXO\|YYm=	MoLsNE0yKM7:TR?=	NXPOe5dNOjUEoHi=		NFnVRY9qdmS3Y3XzJGRPSSCocnHncYVvfGG2aX;uxsBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>	M4fzT\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkGyPVQyLz5{NU[xNlk1OTxxYU6=
ML-1	MlLMSpVv[3Srb36gRZN{[Xl?	Mk\6NUDPxE1?	NV\yfo5ZOjUEoHi=		MlrGbY5kemWjc3XzJINie3Cjc3WtN{Bi[3Srdnn0fUA1NW[xbHS=	NYfidWlrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2NVI6PDFpPkK1OlEzQTRzPD;hQi=>
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OS-RC-2	NGDrW4VCeG:ydH;zbZMhSXO\|YYm=	M{PrWFUxKG6P	MVK0PEBp	NUjle3hDTE2VTx?=	MkPsbY5lfWOnczDj[YxtKGGyb4D0c5Nqew>?	MnzmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzNES3N\|coRjJ2MUS0O\|M4RC:jPh?=
SK-N-AS	MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MWqw5qCUQDBibl2=	NYCyZpVNPDhiaB?=		NVf1Tow3UUN3ME2yO{41KG6P	NHWzclk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEC5PFc6QSd-MkSwPVg4QTl:L3G+
SK-N-DZ	MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M4e1d\|DjiJN6MDDuUS=>	NFTYUZA1QCCq		NXPEfZdIUUN3ME2yNU46KG6P	MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB7OEe5PUc,OjRyOUi3PVk9N2F-
SK-N-SH	NG\KZ29Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NHzNepAx6oDVOECgcm0>	NFq1foY1QCCq		M2PrWWlEPTB;N{KuN{BvVQ>?	MoX5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyOUi3PVkoRjJ2MEm4O\|k6RC:jPh?=
SK-N-BE	NU\3XFh6T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	M4PQUlDjiJN6MDDuUS=>	MUm0PEBp		NXSyeWhMUUN3ME23OU41KG6P	NWLWTHlsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPVg4QTlpPkK0NFk5Pzl7PD;hQi=>
SK-N-AS	MUXBdI9xfG:\|aYOgRZN{[Xl?	NXrWZllMOOLCk{iwJI5O	Mmf2OFghcA>?		MWrwc5RmdnSueTDpcoR2[2WmIHHwc5B1d3OrczDpckBiKGSxc3Wt[IVx\W6mZX70JIZie2irb36=	NH31Tpk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEC5PFc6QSd-MkSwPVg4QTl:L3G+
SK-N-DZ	MoHCRZBweHSxc3nzJGF{e2G7	MUWw5qCUQDBibl2=	M{HOPVQ5KGh?		NXKzcIdXeG:2ZX70cJkhcW6mdXPl[EBieG:ydH;zbZMhcW5iYTDkc5NmNWSncHXu[IVvfCCoYYPobY9v	NH;kfJM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEC5PFc6QSd-MkSwPVg4QTl:L3G+
SK-N-SH	NIm0eWhCeG:ydH;zbZMhSXO\|YYm=	MV[w5qCUPDBibl2=	NFnWdpg1QCCq		MnHrdI91\W62bImgbY5lfWOnZDDhdI9xfG:\|aYOgbY4h[SCmb4PlMYRmeGWwZHXueEBn[XOqaX;u	M4rQcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEm4O\|k6Lz5{NEC5PFc6QTxxYU6=
SK-N-BE	MnLtRZBweHSxc3nzJGF{e2G7	M2HPdVDjiJN2MDDuUS=>	Mlj0OFghcA>?		MYnwc5RmdnSueTDpcoR2[2WmIHHwc5B1d3OrczDpckBiKGSxc3Wt[IVx\W6mZX70JIZie2irb36=	NHL4XFM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEC5PFc6QSd-MkSwPVg4QTl:L3G+
SK-N-AS	NWj5cG8{TnWwY4Tpc44hSXO\|YYm=	NH6wNXYx6oDVOECgcm0>	MoS4OFghcA>?		MVvpcoR2[2W\|IHGg[I9{\S2mZYDlcoRmdnRiY3zlZZZi\2Vib3[gZ4F{eGG\|ZTCzJIFv\CCSQWLQ	NYfYW\|J3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPVg4QTlpPkK0NFk5Pzl7PD;hQi=>
SK-N-DZ	M{nkV2Z2dmO2aX;uJGF{e2G7	M3n0TFDjiJN6MDDuUS=>	M{D0XVQ5KGh?		NXTMcoNjcW6mdXPld{BiKGSxc3Wt[IVx\W6mZX70JINt\WG4YXflJI9nKGOjc4Dhd4UhOyCjbnSgVGFTWA>?	NF3XUJU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEC5PFc6QSd-MkSwPVg4QTl:L3G+
SK-N-SH	M2GxVGZ2dmO2aX;uJGF{e2G7	MYWw5qCUPDBibl2=	NUj3XHd3PDhiaB?=		MWnpcoR2[2W\|IHGg[I9{\S2mZYDlcoRmdnRiY3zlZZZi\2Vib3[gZ4F{eGG\|ZTCzJIFv\CCSQWLQ	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB7OEe5PUc,OjRyOUi3PVk9N2F-
SK-N-BE	NGT2boVHfW6ldHnvckBCe3OjeR?=	NUT0SlV7OOLCk{SwJI5O	MnK1OFghcA>?		MmPKbY5lfWOnczDhJIRwe2VvZHXw[Y5l\W62IHPs[YF3[WenIH;mJINie3Cjc3WgN{BidmRiUFHSVC=>	Ml3jQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyOUi3PVkoRjJ2MEm4O\|k6RC:jPh?=
HCC-LM3	NUjp[3JTT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NELmSIYyNTFyMECgcm0>	M4XzR\|I1NzR6L{eyJIg>	MUjEUXNQ	MlTQbY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYn;0bEB1cW2nLTDhcoQh\G:\|ZT3k[ZBmdmSnboSgcYFvdmW{	NUTmWWh{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPVM6PTZpPkK0NFk{QTV4PD;hQi=>
HepG2	MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M2TK[lEuOTByMDDuUS=>	NIXtNFYzPC92OD:3NkBp	NFTCTWVFVVOR	M2XkeIlvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHLveIghfGmvZT2gZY5lKGSxc3Wt[IVx\W6mZX70JI1idm6nch?=	NUDuZldQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPVM6PTZpPkK0NFk{QTV4PD;hQi=>
SMMC-7721	NEPrPXJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MmnpNU0yODByIH7N	MVSyOE81QC95MjDo	M4DGWmROW09?	M1zmR4lvcGmkaYTzJINmdGxiZ4Lve5RpKGmwIHLveIghfGmvZT2gZY5lKGSxc3Wt[IVx\W6mZX70JI1idm6nch?=	NFvyc5U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEC5N\|k2Pid-MkSwPVM6PTZ:L3G+
HCC-LM3	MlvHRZBweHSxc3nzJGF{e2G7	MkDLOVAhdk1?	MXi0PEBp	M332TGROW09?	NHjxXXdqdmS3Y3XzJINmdGxiYYDvdJRwe2m\|IIPp[45q\mmlYX70cJkhcW5iYTDjZZNx[XOnLXTldIVv\GWwdDDtZY5v\XJiYomgZ4xm[X[jZ3Wgc4Yh[2G\|cHHz[ZMhOyxiODDhcoQhQQ>?	NYC3VYE6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPVM6PTZpPkK0NFk{QTV4PD;hQi=>
HepG2	M1;wWGFxd3C2b4Ppd{BCe3OjeR?=	MWK1NEBvVQ>?	NGrsT5U1QCCq	NFz5WYdFVVOR	MnrNbY5lfWOnczDj[YxtKGGyb4D0c5NqeyC\|aXfubYZq[2GwdHz5JIlvKGFiY3HzdIF{\S2mZYDlcoRmdnRibXHucoVzKGK7IHPs[YF3[WenIH;mJINie3Cjc3XzJFMtKDhiYX7kJFk>	MlnVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyOUO5OVYoRjJ2MEmzPVU3RC:jPh?=
SMMC-7721	MW\BdI9xfG:\|aYOgRZN{[Xl?	Mmq2OVAhdk1?	MWe0PEBp	NHLDOVdFVVOR	NFz1eVRqdmS3Y3XzJINmdGxiYYDvdJRwe2m\|IIPp[45q\mmlYX70cJkhcW5iYTDjZZNx[XOnLXTldIVv\GWwdDDtZY5v\XJiYomgZ4xm[X[jZ3Wgc4Yh[2G\|cHHz[ZMhOyxiODDhcoQhQQ>?	MmTCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyOUO5OVYoRjJ2MEmzPVU3RC:jPh?=
HCC-LM3	M2HRO2Z2dmO2aX;uJGF{e2G7	NHX5VmU2OC9zMECgcm0>	MWSyOEBp	MoLGSG1UVw>?	M1HTdIRm[3KnYYPld{B1cGVibHX2[Yx{KG:oIICtV3RCXDNiYX7kJJAuSWu2wrC=	NUe5TVlnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPVM6PTZpPkK0NFk{QTV4PD;hQi=>
HepG2	MkXTSpVv[3Srb36gRZN{[Xl?	MnTNOVAwOTByIH7N	MYqyOEBp	NGnKVJlFVVOR	MnXx[IVkemWjc3XzJJRp\SCuZY\lcJMhd2ZicD3TWGFVOyCjbnSgdE1Cc3UEoB?=	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB7M{m1Okc,OjRyOUO5OVY9N2F-
SMMC-7721	NEHhWHBHfW6ldHnvckBCe3OjeR?=	NFrPOZM2OC9zMECgcm0>	M4HwS\|I1KGh?	M2PGbWROW09?	M1SxZYRm[3KnYYPld{B1cGVibHX2[Yx{KG:oIICtV3RCXDNiYX7kJJAuSWu2wrC=	MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB7M{m1Okc,OjRyOUO5OVY9N2F-
HCC-LM3	NEPTW2hHfW6ldHnvckBCe3OjeR?=	MUW1NE8yODBibl2=	NH3OSm0zPCCq	MlLwSG1UVw>?	NE\NPINld3ewcnXneYxifGW\|IFLjcE15VCCneIDy[ZN{cW:w	MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB7M{m1Okc,OjRyOUO5OVY9N2F-
HepG2	M1\GTmZ2dmO2aX;uJGF{e2G7	NXTuNXhVPTBxMUCwJI5O	MWOyOEBp	M3z3XmROW09?	MmHZ[I94dnKnZ4XsZZRmeyCEY3ytfGwh\XiycnXzd4lwdg>?	MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDB7M{m1Okc,OjRyOUO5OVY9N2F-
SMMC-7721	M2Cx[WZ2dmO2aX;uJGF{e2G7	NX\zV5NlPTBxMUCwJI5O	MX2yOEBp	MUHEUXNQ	M{LPWoRwf26{ZXf1cIF1\XNiQnPsMZhNKGW6cILld5Nqd25?	NV:5cGxKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwPVM6PTZpPkK0NFk{QTV4PD;hQi=>
FaDu	MkfCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MnnsNVAx6oDHbl2=	NFLzR3Q5NzFyL{GyJIg>		M4ezU4Rqe3CuYYnl[EBiKHOrZ37p[olk[W62IHHu[EBxem:ub37n[YQhTzJxTTDhdpJme3RiYYSgPEBidmRiMUNihKVpKHCxc4SgdoVt\WG\|ZR?=	M2rUflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MEK2OFgzLz5{NECyOlQ5OjxxYU6=
FaDu	MXPGeY5kfGmxbjDBd5NigQ>?	MonHNVAx6oDHbl2=	MUiyM\|QwQC9zMjDo		MmfRbY5lfWOnZDDwNlFY[WZzL1PpdFHDqGW6cILld5Nqd25?	NVLGOWN5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSwNlY1QDJpPkK0NFI3PDh{PD;hQi=>
PC-3	MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MXuwMVExKM7:TR?=	NIjnRYwzPC92OD:3NkBp		MlvobY5pcWKrdIOgZ4VtdCCpcn;3eIghcW5iYn;0bEB1cW2nLTDhcoQh\G:\|ZT3k[ZBmdmSnboSgcYFvdmW{	MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzl7MUKxOkc,OjN7OUGyNVY9N2F-
LNCaP	M1jxXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M3vk[lAuPSEQvF2=	NVz3bY1mOjRxNEivO\|IhcA>?		NG\0eGJqdmirYnn0d{Bk\WyuIHfyc5d1cCCrbjDic5RpKHSrbXWtJIFv\CCmb4PlMYRmeGWwZHXueEBu[W6wZYK=	MlfsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7OUGyNVYoRjJ\|OUmxNlE3RC:jPh?=
RWPE-1	Ml;XS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NVj5PXFEOC1{MDFOwG0>	MYiyOE81QC95MjDo		MWHpcohq[mm2czDj[YxtKGe{b4f0bEBqdiCkb4ToJJRqdWVvIHHu[EBld3OnLXTldIVv\GWwdDDtZY5v\XJ?	MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzl7MUKxOkc,OjN7OUGyNVY9N2F-
Capan-1	MmLZSpVv[3Srb36gRZN{[Xl?	M1\zeFI2NzVyL{GwNEBvVQ>?	M4jhfVgwOjRxNEigbC=>	MX7EUXNQ	NI[4NHJld3ewcnXneYxifGWmIGLvckBuWk6DIHHu[EBxem:2ZXnuJIV5eHKnc4Ppc44h[W6mIHTve45{fHKnYX2gd4lodmGuaX7n	NVmyUFEzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5NlI5QDZpPkKzPVIzQDh4PD;hQi=>
L3.6pl	MWTGeY5kfGmxbjDBd5NigQ>?	MojtNlUwPTBxMUCwJI5O	MYS4M\|I1NzR6IHi=	NETMVY1FVVOR	NY[3d\|BY\G:5boLl[5Vt[XSnZDDSc44hdVKQQTDhcoQheHKxdHXpckBmgHC{ZYPzbY9vKGGwZDDkc5dve3S{ZXHtJJNq\26jbHnu[y=>	MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzl{Mki4Okc,OjN7MkK4PFY9N2F-
CFPAC-1	Mmf6SpVv[3Srb36gRZN{[Xl?	MY[yOU82OC9zMECgcm0>	MkCzPE8zPC92ODDo	NFXlN3NFVVOR	MV\kc5dvemWpdXzheIVlKFKxbjDtVm5CKGGwZDDwdo91\WmwIHX4dJJme3Orb36gZY5lKGSxd37zeJJm[W1ic3nncoFtcW6p	NXW0PHJ1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5NlI5QDZpPkKzPVIzQDh4PD;hQi=>
Capan-1	MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MkfPNlUwPTBxMUCwJI5O	M17uUFQ5KGh?	MkD6SG1UVw>?	MlO2doVlfWOnczDj[YxtKGe{b4f0bEBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>	MoXnQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7MkK4PFYoRjJ\|OUKyPFg3RC:jPh?=
L3.6pl	M2\Idmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NHzhWowzPS93MD:xNFAhdk1?	NG\BSYk1QCCq	MnnHSG1UVw>?	NV\GdHhQemWmdXPld{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?	MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzl{Mki4Okc,OjN7MkK4PFY9N2F-
CFPAC-1	NETQfmFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	Ml;pNlUwPTBxMUCwJI5O	M4ToRVQ5KGh?	NF;6T5ZFVVOR	M3qzZpJm\HWlZYOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>	MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzl{Mki4Okc,OjN7MkK4PFY9N2F-
Capan-1	MVzBdI9xfG:\|aYOgRZN{[Xl?	NGTo[4wzPS93MD:xNFAhdk1?	MkDqOFghcA>?	NHWzbZdFVVOR	M13ZOIlv\HWlZYOgZ4VtdCCpcn;3eIghcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>	M2ixUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OUKyPFg3Lz5{M{myNlg5PjxxYU6=
L3.6pl	M3;LdWFxd3C2b4Ppd{BCe3OjeR?=	MkC3NlUwPTBxMUCwJI5O	M1jqW\|Q5KGh?	MX\EUXNQ	NVjORoxNcW6mdXPld{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?	NXPwPXRKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5NlI5QDZpPkKzPVIzQDh4PD;hQi=>
CFPAC-1	NH7leYlCeG:ydH;zbZMhSXO\|YYm=	MnTjNlUwPTBxMUCwJI5O	NETiSFA1QCCq	MmXaSG1UVw>?	NY\3WnpUcW6mdXPld{Bk\WyuIHfyc5d1cCCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?	NFH2fFk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{myNlg5Pid-MkO5NlI5QDZ:L3G+
HN22	MoPHS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M3j3OlAuOjBibl2=	MUiyOE81QCCq	M17ITmROW09?	MkTtbY5pcWKrdIOgZ4VtdCC4aXHibYxqfHliaX6gZo91cCC2aX3lMUBidmRiZH;z[U0h\GWyZX7k[Y51KG2jbn7ldi=>	M1yx[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OEe3NlM2Lz5{M{i3O\|I{PTxxYU6=
HSC4	Mmn4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NGHRSXAxNTJyIH7N	M4i2dlI1NzR6IHi=	M{[0UmROW09?	NGr1bHBqdmirYnn0d{Bk\WyuII\pZYJqdGm2eTDpckBjd3SqIITpcYUuKGGwZDDkc5NmNSCmZYDlcoRmdnRibXHucoVz	NIn2dHk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{i3O\|I{PSd-MkO4O\|czOzV:L3G+
HN22	MX;BdI9xfG:\|aYOgRZN{[Xl?	NVjQSHd2OC1{MDDuUS=>	MX60PEBp	MUfEUXNQ	M3G2TIlv\HWlZYOgZ4VtdCCjcH;weI9{cXN?	NIDESGk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{i3O\|I{PSd-MkO4O\|czOzV:L3G+
HSC4	M37JU2Fxd3C2b4Ppd{BCe3OjeR?=	NX\4dW1qOC1{MDDuUS=>	MVO0PEBp	MoGxSG1UVw>?	NWTPcotVcW6mdXPld{Bk\WyuIHHwc5B1d3Orcx?=	M17vdVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OEe3NlM2Lz5{M{i3O\|I{PTxxYU6=
HN22	NFrIVm1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MYOwMVIxKG6P	M1HWdFQ5KGh?	NIjzRXRFVVOR	NXLCU2p[cW6mdXPld{BIOSCyaHHz[UBk\WyuIHP5Z4xmKGG{cnXzeOKh	NVXaUo1kRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO4O\|czOzVpPkKzPFc4OjN3PD;hQi=>
HSC4	MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MmHCNE0zOCCwTR?=	NI[wVVA1QCCq	NWraO5hETE2VTx?=	NET0TpNqdmS3Y3XzJGcyKHCqYYPlJINmdGxiY4njcIUh[XK{ZYP0xsA>	M1nnS\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OEe3NlM2Lz5{M{i3O\|I{PTxxYU6=
HN22	M1rvPWZ2dmO2aX;uJGF{e2G7	MorJNE0zOCCwTR?=	M{\vNFQ5KGh?	NHzqZnlFVVOR	MXPzeZBxemW\|c3XzJHNxOSCneIDy[ZN{cW:wwrC=	NFzCSpc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{i3O\|I{PSd-MkO4O\|czOzV:L3G+
HSC4	NGD0dI5HfW6ldHnvckBCe3OjeR?=	M1fO[\|AuOjBibl2=	M{LNcFQ5KGh?	NISzU2NFVVOR	MlXpd5VxeHKnc4Pld{BUeDFiZYjwdoV{e2mxbtMg	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzh5N{KzOUc,OjN6N{eyN\|U9N2F-
Cal62	NIHw[mtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=				M4n4cGlEPTB;M{OgxtEhPCCwTR?=	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzh{NEC2OEc,OjN6MkSwOlQ9N2F-
Hth7	M{O2fWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7				NX\HbnlzUUN3ME2xOUDDuSB{IH7N	M1PyflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OEK0NFY1Lz5{M{iyOFA3PDxxYU6=
Hth83	MmTQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				NVfuV3hmUUN3ME2zOEDDuSB3IH7N	NF63Xm49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{iyOFA3PCd-MkO4NlQxPjR:L3G+
C643	NIHPW\|BIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=				NVTj[4xwUUN3ME23NUDDuSBzMDDuUS=>	NXX1PXFKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO4NlQxPjRpPkKzPFI1ODZ2PD;hQi=>
SW1736	M3;Y[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7				MVHJR\|UxRTN3INMxJFghdk1?	MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzh{NEC2OEc,OjN6MkSwOlQ9N2F-
T241	MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?				MYPJR\|UxRTZ3INMxJFchdk1?	MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzh{NEC2OEc,OjN6MkSwOlQ9N2F-
T351	NEfLTpBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=				M2G5NmlEPTB;NUCgxtEhOTBibl2=	NEfVRpo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{iyOFA3PCd-MkO4NlQxPjR:L3G+
BHP2-7	NYrQZXJTT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=				MYHJR\|UxRTN5INMxJFYhdk1?	Mk\YQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN6MkSwOlQoRjJ\|OEK0NFY1RC:jPh?=
T238	MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?				M37vWWlEPTB;MTy1NFAhyrFiMkCwJI5O	NXuzeW5yRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO4NlQxPjRpPkKzPFI1ODZ2PD;hQi=>
HCT8	MWfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		MoDQO\|IhcA>?	M3W0c2ROW09?	M2TId2lEPTB;MUKuPgKBkcLz4pEJNU46KG6P	MkDFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN{OUmzPFgoRjJ\|Mkm5N\|g5RC:jPh?=
H630	MknQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		MVK3NkBp	M1;q[mROW09?	NV3KXVVPUUN3ME2xNk416oDLwsJihKk{NjFibl2=	MnqwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN{OUmzPFgoRjJ\|Mkm5N\|g5RC:jPh?=
cH630 5-FU-res	MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		MmDwO\|IhcA>?	NHHhVlFFVVOR	NVvEU2lMUUN3ME2xOU426oDLwsJihKkyNjJibl2=	MmO4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN{OUmzPFgoRjJ\|Mkm5N\|g5RC:jPh?=
HCT116	MnHLS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		NYnRdoM4PzJiaB?=	M{XWWmROW09?	M1HNcmlEPTB;MUCuO-KBkcLz4pEJNk4zKG6P	NHn3WlM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{K5PVM5QCd-MkOyPVk{QDh:L3G+
HCT116 p53−/−	Mn[1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		M3GzbFczKGh?	M131RWROW09?	MmDiTWM2OD16LkdihKnDueLCiUGuO{BvVQ>?	NWj5dJpsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOyPVk{QDhpPkKzNlk6Ozh6PD;hQi=>
dHCT116 p21−/−	NXnzUHg3T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		M1nr[\|czKGh?	NX;PWoVOTE2VTx?=	M3v5SmlEPTB;NT655qCKyrIkgJmxMlMhdk1?	NYrlTWFXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOyPVk{QDhpPkKzNlk6Ozh6PD;hQi=>
HT29	MmPKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		M2\Re\|czKGh?	NF7nc5pFVVOR	NYiwVlhQUUN3ME2xOk4{6oDLwsJihKkzNjNibl2=	M{C0OVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|Mkm5N\|g5Lz5{M{K5PVM5QDxxYU6=
LoVo	MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		M1\2VFczKGh?	Mo\5SG1UVw>?	NYjUS4NxUUN3ME21MlHjiIoEsfMAjVAvPiCwTR?=	MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzJ7OUO4PEc,OjN{OUmzPFg9N2F-
RKO	NUfTeZNPT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		M4jQRlczKGh?	MoLGSG1UVw>?	MoDwTWM2OD15LkpihKnDueLCiUKuNkBvVQ>?	MkPrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN{OUmzPFgoRjJ\|Mkm5N\|g5RC:jPh?=
SW480	NYXsfmFjT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		MYS3NkBp	MmDvSG1UVw>?	MWjJR\|UxRTF5LkZihKnDueLCiUCuPEBvVQ>?	MoPxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN{OUmzPFgoRjJ\|Mkm5N\|g5RC:jPh?=
eSW620	MkPhS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		NYrWelhzPzJiaB?=	Mm\BSG1UVw>?	NIGxZmhKSzVyPUmuNgKBkcLz4pEJNk4yKG6P	NX;pZXppRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOyPVk{QDhpPkKzNlk6Ozh6PD;hQi=>
S2	NYTMXoY3TnWwY4Tpc44h[XO\|YYm=				MYfJcohq[mm2aX;uJI9nKFCuYYPtc4RqfW1iZnHsZ4lx[XK3bTDISGFEOSCneIDy[ZN{\WRiaX6gSJJwe2:yaHnsZUBu\Wyjbn;nZZN1\XJiU{KgZ4VtdHNuIFnDOVAhRSByLkCwNVgh\|ryPLh?=	NE\pXlU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUOxO\|Q2OCd-MUmzNVc1PTB:L3G+
COLO205	M3uxUGFvfGmycn;sbYZmemG2aY\lJIF{e2G7		MmrOPVYhcHK\|		NILlUYZCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFPPUG8zODViY3XscJMh[W[2ZYKgPVYhcHK\|IHL5JINmdGy2aYTldkA6PiCjc4PhfUwhUUN3MDC9JFAvODF6IN88UU4>	M4rISVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzNkO0OFMxLz5{MU[zOFQ{ODxxYU6=
PC3	M1HQTmFvfGmycn;sbYZmemG2aY\lJIF{e2G7		MYO5OkBpenN?		NHLpbWxCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGDDN{Bk\WyuczDh[pRmeiB7NjDodpMh[nliY3XscJRqfGW{IEm2JIF{e2G7LDDJR\|UxKD1iMD6wNlQh\|ryPLh?=	NUjTdFJTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG2N\|Q1OzBpPkKxOlM1PDNyPD;hQi=>
A2780	NXfucphjSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		MmXOPVYhcHK\|		M33TPWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iQUK3PFAh[2WubIOgZYZ1\XJiOU[gbJJ{KGK7IHPlcIx1cXSncjC5OkBie3OjeTygTWM2OCB;IECuNFM2KM7:TT6=	NVzvPJhRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG2N\|Q1OzBpPkKxOlM1PDNyPD;hQi=>
HCT116	Mk\ERY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		MVe5OkBpenN?		NF:xWmxCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjDWFEyPiClZXzsd{Bi\nSncjC5OkBpenNiYomgZ4VtdHSrdHXyJFk3KGG\|c3H5MEBKSzVyIE2gNE4xPDhizszNMi=>	NU\jNmVwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG2N\|Q1OzBpPkKxOlM1PDNyPD;hQi=>
HEK293	NWfNRoU2TnWwY4Tpc44h[XO\|YYm=				MVTJcohq[mm2aX;uJI9nKEiGQVOzJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW\|c3XkJIlvKEiHS{K5N{Bk\WyuczD1d4lv\yCdM1jdZYNmfHmuYYTl[EBpfW2jbjDobZN1d26nIFi0JJBmeHSrZHWgZZMhe3Wkc4TyZZRmKGK7IIPjbY51cWyuYYTpc44h[2:3boTpcoctKEmFNUCgQUAxNjByMkGg{txONg>?	NEnYbm89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkO0OFcxOSd-MkKzOFQ4ODF:L3G+
HEK293	Ml;NSpVv[3Srb36gZZN{[Xl?				MnruTY5pcWKrdHnvckBw\iCKRFHDNUApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCKRVuyPVMh[2WubIOgeZNqdmdiW{PIYYFk\XS7bHH0[YQhcHWvYX6gbIl{fG:wZTDIOEBx\XC2aXTlJIF{KHO3YoP0doF1\SCkeTDzZ4lvfGmubHH0bY9vKGOxdX70bY5oNCCLQ{WwJF0hOC5yMEK1JO69VS5?	NWXSOItyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKzOFQ4ODFpPkKyN\|Q1PzBzPD;hQi=>
HEK293	NH7DSmVHfW6ldHnvckBie3OjeR?=				NW\Q[mdIUW6qaXLpeIlwdiCxZjDISGFEPiBqdX7rco94diCxcnnnbY4qKGW6cILld5Nm\CCrbjDISWszQTNiY3XscJMhfXOrbnegX\|NJZWGlZYT5cIF1\WRiaIXtZY4hcGm\|dH;u[UBJPCCyZYD0bYRmKGG\|IIP1ZpN1emG2ZTDifUB{[2mwdHnscIF1cW:wIHPveY51cW6pLDDJR\|UxKD1iMD6wNVEh\|ryPLh?=	NInlTXk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkO0OFcxOSd-MkKzOFQ4ODF:L3G+
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MM1S	MmDGR5l1d3SxeHnjbZR6KGG\|c3H5		NX7tUHF7OjRiaILz		NWT4NnhpS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVU1zUzDj[YxteyCjc4Pld5Nm\CCjczDndo94fGhiaX7obYJqfGmxbjDh[pRmeiB{NDDodpMh[nliTWTUJIF{e2G7	MorJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjdzOE[2O\|YoRjJ5MUi2Olc3RC:jPh?=
OCI-LY1	M3vEVmN6fG:2b4jpZ4l1gSCjc4PhfS=>		NFjTW5gzPCCqcoO=		NUXudFJKS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hV0OLLVzZNUBk\WyuczDhd5Nme3OnZDDhd{Boem:5dHigbY5pcWKrdHnvckBi\nSncjCyOEBpenNiYomgUXRVKGG\|c3H5	M3nzNVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5MUi2Olc3Lz5{N{G4OlY4PjxxYU6=
SUDHL4	MmrER5l1d3SxeHnjbZR6KGG\|c3H5		Mo[5NlQhcHK\|		MkjCR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gV3VFUEx2IHPlcIx{KGG\|c3Xzd4VlKGG\|IHfyc5d1cCCrbnjpZol1cW:wIHHmeIVzKDJ2IHjyd{BjgSCPVGSgZZN{[Xl?	NHrSdlA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{G4OlY4Pid-MkexPFY3PzZ:L3G+
MV4-11	NXLYWnRYTnWwY4Tpc44h[XO\|YYm=	M4\WO\|UxKG6P	NGLwdGEzPCCqcoO=		MoPETY5lfWO2aX;uJI9nKEiGQVO2JIRm\3KjZHH0bY9vKGmwIHj1cYFvKE2YND2xNUBk\WyuczDheEA2OCCwTTDh[pRmeiB{NDDodpMh[nliV3XzeIVzdiCkbH;0JI1mfGixZB?=	M3ewfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NUi5OFQyLz5{OUW4PVQ1OTxxYU6=
MV4-11	NGf6NoFHfW6ldHnvckBie3OjeR?=	MVe1NEBvVQ>?	NETKU5QzKHSxIEK0JIhzew>?		NWnsVJBDUW6qaXLpeIlwdiCxZjDISGFEPiCrbjDoeY1idiCPVkStNVEh[2WubIOgZZN{\XO\|ZXSgZZMhcW6mdXP0bY9vKG:oIHHsdIhiNXS3YoXsbY4hcHmyZYLhZ4V1gWyjdHnvckBifCB3MDDuUUBi\nSncjCyJJRwKDJ2IHjyd{BjgSCZZYP0[ZJvKGKub4SgcYV1cG:m	NYHJcYxLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm1PFk1PDFpPkK5OVg6PDRzPD;hQi=>
MV4-11	NUXhcZh2S2WubDDjfYNt\SCjcoLld5Qh[XO\|YYm=	MnfvN\|AhfG9iNUCgcm0>	MWKyOEBpenN?		M4nsR2NmdGxiY4njcIUh[XK{ZYP0JIlvKGi3bXHuJG1XPC1zMTDj[YxteyCjc4Pld5Nm\CCjczDhZ4N2dXWuYYTpc44h[XRic4XiMWcyKHCqYYPlJIF1KDNyIITvJFUxKG6PIHHmeIVzKDJ2IHjyd{BjgSCycn;wbYRqfW1iaX;kbYRmKHO2YXnubY5oNWKjc3XkJIZtd3diY4n0c41mfHKrYzDt[ZRpd2R?	MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTV6OUS0NUc,Ojl3OEm0OFE9N2F-
MV4-11	M3PvTWFxd3C2b4Ppd{Bie3OjeR?=	MnXEN\|Ahdk1?	MoezNlQhfG9iNEigbJJ{		MXHJcoR2[3Srb36gc4Yh[XCxcITvd4l{KGmwIHj1cYFvKE2YND2xNUBk\WyuczDheEA{OCCwTTDh[pRmeiB{NDD0c{A1QCCqcoOgZpkhSW6wZYjpckBXNVCLIIP0ZYlvcW6pIHLhd4VlKG[ub4egZ5l1d22ndIL5	MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTd\|OEm1N{c,Ojl5M{i5OVM9N2F-

... 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.

Bio Calculators

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Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

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Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

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The Serial Dilution Calculator Equation

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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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To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

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Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
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Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2021-01-06)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04341311	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	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

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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

RGFP966 : HDAC3-selective, IC50=80 nM.
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.

Related HDAC Products

LMK-235 ^New

LMK-235 is a selective inhibitor of HDAC4 and HDAC5 with IC50 of 11.9 nM and 4.2 nM, respectively.
CAY10603 ^New

CAY10603 (BML-281) is a potent and selective HDAC6 inhibitor with IC50 of 2 pM, >200-fold selectivity over other HDACs.
Domatinostat (4SC-202) ^New

Domatinostat (4SC-202) is a selective class I HDAC inhibitor with IC50 of 1.20 μM, 1.12 μM, and 0.57 μM for HDAC1, HDAC2, and HDAC3, respectively. Also displays inhibitory activity against Lysine specific demethylase 1 (LSD1). Phase 1.
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.
Entinostat (MS-275)

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.
RGFP966

RGFP966 is an HDAC3 inhibitor with IC50 of 0.08 μM in cell-free assay, exhibits > 200-fold selectivity over other HDAC.
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)