Vemurafenib (PLX4032)

Name: Vemurafenib (PLX4032)
Brand: Selleck Chemicals
SKU: S1267
Rating: 5 (453 reviews)

For research use only.

Catalog No.S1267 Synonyms: RG7204

453 publications

Vemurafenib (PLX4032) Chemical Structure

CAS No. 918504-65-1

Vemurafenib (PLX4032, RG7204) is a novel and potent inhibitor of B-Raf^V600E with IC50 of 31 nM in cell-free assay. 10-fold selective for B-Raf^V600E over wild-type B-Raf in enzymatic assays and the cellular selectivity can exceed 100-fold. Vemurafenib (PLX4032, RG7204) induces autophagy.

Selleck's Vemurafenib (PLX4032) has been cited by 453 publications

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

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Cancer Cell, 2020, 37(1):85-103

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Cancer Discov, 2019, 9(7):852-871

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Cancer Cell, 2019, 36(1):68-83

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Science, 2018, 361(6405)

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

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Cancer Cell, 2018, 33(2):322-336

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Cancer Cell, 2018, 33(5):890-904.e5

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Cancer Cell, 2018, 9;34(1):56-68.e9

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Cell Metab, 2018, 28(6):817-832

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Nature, 2017, 547(7664):453-457

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Nature, 2016, 538(7626):477-482

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Nature, 2016, 10.1038/nature19347

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Science, 2016, 352(6282):189-96

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Nat Biotechnol, 2016, 34(2):184-191

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Nat Med, 2016, 22(9):1056-61

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Nat Med, 2016, 22(6):624-31

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Cell Stem Cell, 2016, 19(6):738-751

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Cancer Cell, 2016, 12;30(3):485-498

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Nature, 2015, 10.1038/nature14336

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Genes Dev, 2020, 1;34(9-10):637-649

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Cell Rep, 2020, 31(11):107764

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Oncogene, 2020, 39(20):4132-4154

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Sci Signal, 2020, 28;13(629)

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Br J Cancer, 2020, 10.1038/s41416-020-0751-8

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J Clin Endocrinol Metab, 2020, dgaa656

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Mol Ther Oncolytics, 2020, 18:83-99

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Cells, 2020, 13;9(5) pii: E1209

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Cell Commun Signal, 2020, 18(1):156

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Mol Oncol, 2020, 24

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Aging (Albany NY), 2020, 12(1):138-155

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Biomolecules, 2020, 10(10)E1395

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Antioxidants (Basel), 2020, 5;9(5) pii: E384

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Front Oncol, 2020, 3;10:442

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Biochem Pharmacol, 2020, 171:113716

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J Transl Med, 2020, 11;18(1):192

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Int J Mol Sci, 2020, 18;21(8):2825

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J Biol Chem, 2020, jbc.RA120.014615

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Cancer Cell Int, 2020, 19;20:58

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Cancer Manag Res, 2020, 12:7231-7250

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BMC Cancer, 2020, 20(1):129

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Pathol Oncol Res, 2020, 10.1007/s12253-020-00834-y

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J Chemother, 2020, 32(8):437-444

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Cells, 2020, 7;9(1). pii: E142

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Pharmaceuticals (Basel), 2020, 14(1)E23

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Cancer Lett, 2020, S0304-3835(20)30635-2

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Cancers (Basel), 2020, 12(8):E2085

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Apoptosis, 2020, 25(3-4):179-191

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Transl Oncol, 2020, 13(2):441-451

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Data Brief, 2020, 22;30:105610

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Commun Biol, 2020, 2;3(1):154

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Cancers (Basel), 2020, 12(7):E1972

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Clin Cancer Res, 2020, 10.1158

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Neoplasia, 2020, 22(10):470-483

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Oncogenesis, 2020, 9(7):64

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Endocrine, 2020, 10.1007/s12020-020-02417-y

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Nat Cell Biol, 2019, 21(6):778-790

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EMBO J, 2019, 38(15):e95874

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Cell Rep, 2019, 26(1):65-78

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Cell Rep, 2019, 29(3):573-588

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Cell Death Differ, 2019, 26(7):1267-1282

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J Control Release, 2019, 309:158-172

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Oncogene, 2019, 38(12):2005-2019

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Stem Cell Reports, 2019,

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Cancer Lett, 2019, 451:79-91

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Cancer Lett, 2019, 451:11-22

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J Exp Clin Cancer Res, 2019, 38(1):56

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Cancers (Basel), 2019, 11(10)

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Pigment Cell Melanoma Res, 2019, 10.1111/pcmr.12824

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Clin Epigenetics, 2019, 11(1):196

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Cell Death Dis, 2019, 10(5):342

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Acta Neuropathol Commun, 2019, 7(1):128

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Endocr Relat Cancer, 2019, 26(1):197-214

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Mol Oncol, 2019, 13(9):1836-1854

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Mol Oncol, 2019, 13(2):480-494

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J Cancer, 2019, 10(16):3819-3829

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Mol Cancer Res, 2019, 10.1158/1541-7786.MCR-19-0257

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ACS Chem Biol, 2019, 10.1021/acschembio-00191

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Int J Mol Sci, 2019, 20(17)E4203

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Int J Mol Sci, 2019, 20(18)

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Int J Mol Sci, 2019, 20(9)

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Sci Rep, 2019, 9(1):636

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Apoptosis, 2019, 24(7-8):596-611

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Mol Pharmacol, 2019, 96(1):36-46

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PLoS Comput Biol, 2019, 15(6):e1007034

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Mol Carcinog, 2019, 58(9):1680-1690

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Mol Carcinog, 2019, 58(11):2149-2160

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Front Pharmacol, 2019, 10:30

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Tissue Eng Part A, 2019, 10.1089/ten.TEA.2018.0210

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J Cell Biochem, 2019, 120(4):5315-5325

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Invest Ophthalmol Vis Sci, 2019, 60(7):2764-2772

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BMC Cancer, 2019, 19(1):266

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Endocrine, 2019, 10.1007/s12020-019-02028-2

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Endocrine, 2019, 64(2):406-413

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Transl Oncol, 2019, 12(7):951-958

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Oncol Rep, 2019, 41(1):570-578

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Exp Dermatol, 2019, 10.1111/exd.14010

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Hum Cell, 2019, 10.1007/s13577-019-00270-4

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Photodermatol Photoimmunol Photomed, 2019, 10.1111/phpp.12520

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ACS Chem Biol, 2019, 14(7):1426-1435

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Sci Rep, 2019, 9(1):10369

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Cancer Res, 2019, 79(19):5074-5087

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Exp Gerontol, 2019, 126:110691

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Cancers (Basel), 2019, 20;12(1). pii: E28

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Mol Ther Nucleic Acids, 2019, 18:727-738

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Oncotarget, 2019, 10(18):1669-1687

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Mol Cell Biol, 2019, 39(14)

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Nat Biomed Eng, 2018, 2(8):578-588

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Mol Cell, 2018, 69(6):923-937

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Nat Commun, 2018, 9(1):4775

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Nat Commun, 2018, 9(1):3440

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J Exp Med, 2018, 215(7):1913-1928

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Clin Cancer Res, 2018, 10.1158/1078-0432.CCR-18-0693

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Cancer Immunol Res, 2018, 10.1158/2326-6066

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Cancer Res, 2018, 78(2):436-450

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Cancer Res, 2018, 78(4):1017-1030

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Cancer Res, 2018,

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J Control Release, 2018, 277:48-56

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Mol Cancer, 2018, 17(1):145

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Oncogene, 2018, 37(7):944-952

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Oncogene, 2018, 37(12):1576-1593

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Oncogene, 2018, 37(24):3275-3289

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Oncogene, 2018,

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Adv Healthc Mater, 2018, 7(17):e1800533

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J Exp Clin Cancer Res, 2018, 37(1):318

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Pigment Cell Melanoma Res, 2018, 31(2):253-266

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Cell Death Dis, 2018, 9(2):29

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Cell Chem Biol, 2018, 25(2):175-184

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Oncoimmunology, 2018, 7(8):e1450127

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Bioinformatics, 2018, 34(17):i997-i1004

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Bioinformatics, 2018, 34(23):4079-4086

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Mol Cancer Ther, 2018, 17(1):84-95

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Mol Cancer Ther, 2018, 17(7):1416-1429

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Mol Cancer Ther, 2018, 17(4):806-813

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Endocr Relat Cancer, 2018, 25(1):99-109

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Endocr Relat Cancer, 2018, 25(4):471-480

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Mol Oncol, 2018, 12(6):869-882

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Mol Oncol, 2018, 12(1):74-88

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Mol Oncol, 2018, 12(2):224-238

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Mol Cell Proteomics, 2018, 17(10):1892-1908

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Cancer Biomark, 2018, 23(1):67-77

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Neoplasia, 2018, 20(11):1121-1134

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Int J Mol Sci, 2018, 19(4)

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ACS Med Chem Lett, 2018, 9(12):1199-1204

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Cell Signal, 2018, 42:30-43

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Life Sci, 2018, 206:35-44

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BMC Cancer, 2018, 18(1):675

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BMC Cancer, 2018, 18(1):1219

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Biochimie, 2018, 148:1-11

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Melanoma Res, 2018, 28(5):390-397

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Melanoma Res, 2018, 28(6):536-546

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Melanoma Res, 2018, 28(6):521-526

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Biol Chem, 2018, 399(7):649-659

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PLoS One, 2018, 13(4):e0195956

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Onco Targets Ther, 2018, 11:8293-8299

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BMC Syst Biol, 2018, 12(1):33

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Med Sci Monit, 2018, 24:3002-3010

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Mol Biol (Mosk), 2018, 52(3):466-473

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Purity & Quality Control

Choose Selective Raf Inhibitors

Biological Activity

Description

Features

A novel and potent inhibitor of the B-RAF^V600E oncoprotein.

Targets

SRMS ^[1] (Cell-free assay)	ACK1 ^[1] (Cell-free assay)	B-Raf (V600E) ^[1] (Cell-free assay)	C-Raf ^[1] (Cell-free assay)	MAP4K5 (KHS1) ^[1] (Cell-free assay)	View More
18 nM	19 nM	31 nM	48 nM	51 nM	View More

In vitro

PLX4032 inhibits B-RAF^V600E, C-RAF, as well as wildtype B-RAF, with IC50 of 31 nM, 48 nM and 100 nM, respectively. PLX4032 also inhibits several non-RAF kinases, including ACK1, KHS1, and SRMS, with IC50 of 18 nM to 51 nM. ^[1] In melanoma cell lines, the inhibitory effect by PLX4032 depends on B-RAF mutational status, because PLX4032 potently inhibits those harboring B-RAF V600 mutants, including V600E, V600D, V600K, and V600R, but not wildtype or other mutants. The IC50 values of PLX4032 on these cells, including MALME-3M, Colo829, Colo38, A375, SK-MEL28, and A2058, ranges from 20 nM to 1 μM. In these cells, PLX4032 (0.1 μM to 30 μM) also inhibits the phosphorylation of both MEK1/2 and ERK1/2. ^[2] PLX4032 is highly effective in the treatment of melanoma, for its ability of inhibiting B-RAF^V600E. However, PLX4032 displays limited effect in colon cancer patients that also carrying B-RAF^V600E oncoprotein. The reason for this is that, in colon cancer cells, B-RAF^V600E inhibition by PLX4032 results in a rapid feedback EGFR activation, which compensates for the PLX4032-inhibited cell proliferation. ^[3]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
SKMEL19	M{TCUGZ2dmO2aX;uJGF{e2G7	M3z6RlYh\|ryP	MVe0PEBp	NIDqcmJFVVOR	NHfBWHpVemmpZ3Xyd{BGWiC\|dILld5M>	MnvDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN\|NkKyOFAoRjJ\|M{[yNlQxRC:jPh?=
VMM12	NWXuWZFSTnWwY4Tpc44hSXO\|YYm=	MmPLN{DPxE1?	NWW1UVB7PDhiaB?=	MYjEUXNQ	NEnjcY5KdmO{ZXHz[ZMh[2:ubHHn[Y4he3mwdHjld4l{KGGwZDDk[YNz\WG\|ZYOgTWwuQSCneIDy[ZN{cW:w	M2jMVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OUi5OVA3Lz5{NUm4PVUxPjxxYU6=
C4	MWDGeY5kfGmxbjDBd5NigQ>?	M33lclMh\|ryP	NEfOZ5o1QCCq	NEW4NnFFVVOR	M1;hOmlv[3KnYYPld{Bkd2yuYXflckB{gW62aHXzbZMh[W6mIHTlZ5Jm[XOnczDJUE05KGW6cILld5Nqd25?	NYfJepRzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW5PFk2ODZpPkK1PVg6PTB4PD;hQi=>
Calu-6	MoT6SpVv[3Srb36gRZN{[Xl?	M4XqeVHjiIoQvF2=	NIDLWZYyKGh?	NV3TOIdCTE2VTx?=	MYTBZ5RqfmG2ZYOgUWVMN0WUSzDpckBk\WyuczD3bZRpKHerbHSteJlx\SCEUlHG	NFv1ZVY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEG3PVcxPSd-MkCxO\|k4ODV:L3G+
PC	MkDyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		MUK5OkBp		NF7lUZVGSzVyPjCxNFAxKG6P	MkDqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl6OEC3PVIoRjF7OEiwO\|kzRC:jPh?=
TPC-1 (RET/PTC1)	MmHRS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		NF\O[4I6PiCq		NIHlR4RGSzVy4polNVAxOCCwTR?=	NGDHXos9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUi4NFc6Oid-MUm4PFA4QTJ:L3G+
CAL62 (KRAS G12R) > 1000 > 1000	MmLFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		NFTWVXU6PiCq		M4PCNGVEPTB-IEGwNFAhdk1?	M1LYd\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7OEiwO\|kzLz5zOUi4NFc6OjxxYU6=
HTH7 (NRAS Q61R)	M4Dvemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		MWe5OkBp		NYLwNXNNTUN3MPMJqUAyODByIH7N	M3H5O\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7OEiwO\|kzLz5zOUi4NFc6OjxxYU6=
C643 (HRAS G13R)≥ 500	M1PIN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7		MV:5OkBp		MWrFR\|UxKOLLpTC1NFAhdk1?	MmC3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl6OEC3PVIoRjF7OEiwO\|kzRC:jPh?=
BCPAP (BRAF WT/V600E)	M1jQc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7		NFTZWnc6PiCq		MknESWM2OD15ODDuUS=>	M{\tbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7OEiwO\|kzLz5zOUi4NFc6OjxxYU6=
BHT101 (BRAF WT/V600E)	NEGxZWxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		NHHyPJI6PiCq		M3P5VGVEPTB;OUegcm0>	MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTh6MEe5Nkc,OTl6OEC3PVI9N2F-
SW1736 (BRAF WT/V600E)	NWjMOXpbT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		MnjSPVYhcA>?		MXrFR\|UxRTJ7IH7N	MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTh6MEe5Nkc,OTl6OEC3PVI9N2F-
8505C (BRAF V600E/V600E)	MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		NUeweWNMQTZiaB?=		MlPISWM2OD13NzDuUS=>	MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTh6MEe5Nkc,OTl6OEC3PVI9N2F-
ARO	NEDVUnpHfW6ldHnvckBCe3OjeR?=	NWDqR\|NPOTBizszN	Mm[4O\|IhcA>?	MmfySG1UVw>?	NIjHdJBKdmS3Y3XzJJRp\SC{ZXX4dJJme3Orb36gc4YhfGinIF7JV{BxfW2y	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDR3OEC1N{c,OTh2NUiwOVM9N2F-
A375	M3rvdWFxd3C2b4Ppd{BCe3OjeR?=	NWm2WJZ7OTBizszN		MWLEUXNQ	NVrNVG9wWHKxbX;0[ZMh[XCxcITveIlkKGSnYYTo	NX7kNnVyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi0OVgxPTNpPkG4OFU5ODV\|PD;hQi=>
TPCI	MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NVvp[2UzOTByIN88US=>	MU[5OkBp	NGHifWJFVVOR	M2XqdGlEPTB;MUCuO\|ch\|ryP	NXjOdGNJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUi0OVgxPTNpPkG4OFU5ODV\|PD;hQi=>
ARO	NGn5ZVBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M3LDNlExOCEQvF2=	NGHMOlk6PiCq	NXr1bpBQTE2VTx?=	MnjmTWM2OD1{MEWgcm0>	M3zwRVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6NEW4NFU{Lz5zOES1PFA2OzxxYU6=
NPA	MkfFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M2HHRVExOCEQvF2=	NUXubJRWQTZiaB?=	MmnPSG1UVw>?	NULOd5d3UUN3ME2yOkBvVQ>?	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDR3OEC1N{c,OTh2NUiwOVM9N2F-
A375	MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M2L4blExOCEQvF2=	M37PfFk3KGh?	M{fzb2ROW09?	MorlTWM2OD12NzDuUS=>	MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDR3OEC1N{c,OTh2NUiwOVM9N2F-
UKF-NB-3 (ABCB1)	NV\aTWNZTnWwY4Tpc44hSXO\|YYm=	M{C5XlEvOjViwsXN	MoPZNkBp	NXLSOY9oTE2VTx?=	NWjLcXpWTW6qYX7j[ZMh[WOldX31cIF1cW:wIH;mJJRp\SCobIXvdoV{[2WwdDDBRmNDOSC\|dXLzeJJifGVicnjv[IFucW6nIEGyNy=>	NYntZ5MzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS3N\|U4PjZpPkK0O\|M2PzZ4PD;hQi=>
UKF-NB-3	MWHGeY5kfGmxbjDBd5NigQ>?	MnTwNU4zPSEEtV2=	NX;lcG5{OiCq	MV7EUXNQ	MVHTbYdvcW[rY3HueIx6KGGoZnXjeJMhd25iYXPjeY12dGG2aX;uJI9nKHSqZTDmcJVwemW\|Y3XueEBCSkOEMTDzeYJ{fHKjdHWgdohw\GGvaX7lJFEzOw>?	NVX5cmQzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS3N\|U4PjZpPkK0O\|M2PzZ4PD;hQi=>
A375 (BRAFV600E)	M4LNVmZ2dmO2aX;uJGF{e2G7		M{PqcVghcA>?	MlnVSG1UVw>?	NXXPRopEUW6lcnXhd4V{KGmwdILhZ4VtdHWuYYKgVm9UKGGwZDDOU{Bt\X[nbIO=	NGPI[Ig9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUO2N\|Y1PCd-MkWzOlM3PDR:L3G+
A375P	M3Hr[WFvfGmycn;sbYZmemG2aY\lJIF{e2G7				NFvPTXRCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFGzO\|VRKGOnbHzzMEBKSzVyIE2gNE4zPTRizszNMi=>	NYD1OoM3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK0OlAxOzBpPkKyOFYxODNyPD;hQi=>
A375	Mm\yRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?				MXnBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEF\|N{WgZ4VtdHNiZYjwdoV{e2mwZzDCMXJi\iCYNkCwSUBufXSjboSgZY5lKHerbHSgeJlx\SCUYYOsJGlEPTBiPTCwMlMyKM7:TT6=	M3\ZbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OEC4PVEyLz5{MkiwPFkyOTxxYU6=
A375P	NGjHfFlCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NEPGS4M1QCCqcoO=		MUjBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEF\|N{XQJINmdGy\|IHHmeIVzKDR6IHjyd{BjgSCPVGSgZZN{[XluIFnDOVAhRSByLkK1JO69VS5?	NFL4eHY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEGyPFQyOCd-MkSxNlg1OTB:L3G+
A375	NEjTXIdEgXSxdH;4bYNqfHliYYPzZZk>		MXW3NkBpenN?		NV;XdlFSS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hSTN5NTDj[YxteyCjZoTldkA4OiCqcoOgZpkhVVSWIHHzd4F6NCCLQ{WwJF0hOC5zODFOwG0v	NIX5[\|g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEKxOVgyQCd-MkSyNVU5OTh:L3G+
SK-MEL-28	NXL1e2o4S3m2b4TvfIlkcXS7IHHzd4F6				M1;mWWN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHNMNU2HTD2yPEBk\WyuczDlfJBz\XO\|aX7nJGIuemGoIG[2NFBGKG23dHHueEwhUUN3MDC9JFAvOSEQvF2u	MnjuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2N{G0OlYoRjJ2NEexOFY3RC:jPh?=
M229	NVn0UYUyS3m2b4TvfIlkcXS7IHHzd4F6				M4jBdGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJG0zOjliY3XscJMh\XiycnXzd4lv\yCELYLh[kBXPjByRTDteZRidnRuIFnDOVAhRSByLkGg{txONg>?	M4PuelxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NEexOFY3Lz5{NES3NVQ3PjxxYU6=
M263	NHO0ZoFEgXSxdH;4bYNqfHliYYPzZZk>				NUf3O4lsS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVTJ4MzDj[YxteyCneIDy[ZN{cW6pIFKtdoFnKFZ4MEDFJI12fGGwdDygTWM2OCB;IECuNUDPxE1w	NGHoR4E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES3NVQ3Pid-MkS0O\|E1PjZ:L3G+
M321	NGnXWmJEgXSxdH;4bYNqfHliYYPzZZk>				NUC5XVF6S3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVTN{MTDj[YxteyCneIDy[ZN{cW6pIFKtdoFnKFZ4MEDFJI12fGGwdDygTWM2OCB;IECuNUDPxE1w	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR5MUS2Okc,OjR2N{G0OlY9N2F-
M238	MmHrR5l1d3SxeHnjbZR6KGG\|c3H5				MXLDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDNNlM5KGOnbHzzJIV5eHKnc4PpcochSi2{YX[gWlYxOEVibYX0ZY51NCCLQ{WwJF0hOC5zIN88UU4>	NWflVpJpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0O\|E1PjZpPkK0OFcyPDZ4PD;hQi=>
M262	M2HnRmN6fG:2b4jpZ4l1gSCjc4PhfS=>				MmrGR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUVI3OiClZXzsd{BmgHC{ZYPzbY5oKEJvcnHmJHY3ODCHIH31eIFvfCxiSVO1NEA:KDBwMTFOwG0v	MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR5MUS2Okc,OjR2N{G0OlY9N2F-
M249	MYTDfZRwfG:6aXPpeJkh[XO\|YYm=				MUnDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDNNlQ6KGOnbHzzJIV5eHKnc4PpcochSi2{YX[gWlYxOEVibYX0ZY51NCCLQ{WwJF0hOC5zIN88UU4>	MoLrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2N{G0OlYoRjJ2NEexOFY3RC:jPh?=
M14	M3vWWWN6fG:2b4jpZ4l1gSCjc4PhfS=>				MVrDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDNNVQh[2WubIOg[ZhxemW\|c3nu[{BPWkGVIFexNmMhdXW2YX70MEBKSzVyIE2gNE4yPSEQvF2u	MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDR5MUS2Okc,OjR2N{G0OlY9N2F-
SK-MEL-28	MkHrRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		MWi2PEBpenN?		NV74eVMzSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDTT{1OTUxvMkigZ4VtdHNiaHHyZo9zcW6pIFLSRWYhXjZyMFWgcZV1[W62IHHmeIVzKDZ6IHjyd{BjgSCPVGOgZZN{[XluIFnDOVAhRSByLkS4JO69VS5?	MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDV6OEC3N{c,OjR3OEiwO\|M9N2F-
insect cell	NFXDXohHfW6ldHnvckBie3OjeR?=		MnL2OlAhdWmwcx?=		MmPjTY5pcWKrdHnvckBw\iCodXzsJIxmdme2aDDoeY1idiCELWLh[kBXPjByRTDteZRidnRiZYjwdoV{e2WmIHnuJIJi[3Wub4\pdpV{KGmwZnXjeIVlKGmwc3XjeEBk\WyuczDhd5Nme3OnZDDhd{Bc\2GvbXGtN\|NRZWmwY3;ydI9z[XSrb36gbY51dyCPRVugZYZ1\XJiNkCgcYlveyCkeTDzZ4lvfGmubHH0bY9vKGOxdX70bY5oNCCLQ{WwJF0hOC5yM{Gg{txONg>?	M{DPfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUCwN\|E2Lz5{NEmwNFMyPTxxYU6=
MALME-3M	NUjUUFg4TnWwY4Tpc44h[XO\|YYm=		MoDINUBpeg>?		NVLEbWpVUW6qaXLpeIlwdiCxZjDCMXJi\iCYNkCwSUBufXSjboStcYVlcWG2ZXSgSZJsKHCqb4PwbI9zgWyjdHnvckBqdiCqdX3hckBOSUyPRT2zUUBk\WyuczDh[pRmeiBzIHjyJIJ6KG[udX;y[ZNk\W6lZTDhcoFtgXOrczygTWM2OCB;IECuNFYyKM7:TT6=	MmLMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MECzNVUoRjJ2OUCwN\|E2RC:jPh?=
A375	Ml;LSpVv[3Srb36gZZN{[Xl?		M{XVO\|EhcHJ?		NX71W\|d7UW6qaXLpeIlwdiCxZjDCMXJi\iCYNkCwSUBufXSjboStcYVlcWG2ZXSgSZJsKHCqb4PwbI9zgWyjdHnvckBqdiCqdX3hckBCOzd3IHPlcIx{KGGodHXyJFEhcHJiYomg[ox2d3Knc3PlcoNmKGGwYXz5d4l{NCCLQ{WwJF0hOC5zOTFOwG0v	NVm4TplYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFA{OTVpPkK0PVAxOzF3PD;hQi=>
COLO205	M3jhTmN6fG:2b4jpZ4l1gSCjc4PhfS=>		MlTGOEBl[Xm\|		MnrzR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gR29NVzJyNTDj[YxteyCjZoTldkA1KGSjeYOgZpkhS2WubGTpeIVzNUeubzDhd5NigSxiRVO1NEA:KDBwMkSg{txONg>?	MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyMEOxOUc,OjR7MECzNVU9N2F-
WM266.4	MWDBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		NVLaW\|VVPDhiaILz		NX7neopOSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDXUVI3Pi52IHPlcIx{KGGodHXyJFQ5KGi{czDifUBOXFRiYYPzZZktKEmFNUCgQUAxNjB4IN88UU4>	Ml7PQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV{NkewNFYoRjJ3Mk[3NFA3RC:jPh?=
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SK-MEL-32	NIXuUVlEgXSxdH;4bYNqfHliYYPzZZk>				MWTDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDTT{1OTUxvM{KgZ4VtdHNuIFnDOVAhRSByLkOxJO69VS5?	M{LDOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NE[xPFI4Lz5{OUS2NVgzPzxxYU6=
WM266.4	NYHiOY9iSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		MWe0PEBpenN?		MmTBRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCZTUK2Ok41KGOnbHzzJIFnfGW{IES4JIhzeyCkeTDNWHQh[XO\|YYmsJGdKPTBiPTCwMlIyKM7:TT6=	MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTl2MES2N{c,Ojl7NEC0OlM9N2F-
A375	NIPxUYNCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NIjRN401QCCqcoO=		MVvBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKEF\|N{WgZ4VtdHNiYX\0[ZIhPDhiaILzJIJ6KE2WVDDhd5NigSxiR1m1NEA:KDBwOUWg{txONg>?	NXLzd4hRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm5OFA1PjNpPkK5PVQxPDZ\|PD;hQi=>
HT-29	NGf1[VFCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NWDVOWs{PDhiaILz		NEDwZWlCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjUMVI6KGOnbHzzJIFnfGW{IES4JIhzeyCkeTDNWHQh[XO\|YYmsJGdKPTBiPTCxMlg5KM7:TT6=	NU[wUGt7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm5OFA1PjNpPkK5PVQxPDZ\|PD;hQi=>
WM1361	MnrURY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		M1HITVQ5KGi{cx?=		NGDEO2JCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGfNNVM3OSClZXzsd{Bi\nSncjC0PEBpenNiYomgUXRVKGG\|c3H5MEBIUTVyIE2gNlAvQCEQvF2u	MkOyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl7NEC0OlMoRjJ7OUSwOFY{RC:jPh?=
HCT116	NEHrfm5CdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NWfJenc5PDhiaILz		M2XNXGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFPUNVE3KGOnbHzzJIFnfGW{IES4JIhzeyCkeTDNWHQh[XO\|YYmsJGdKPTBiPTCyOU4zKM7:TT6=	NGDSZnU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUm0NFQ3Oyd-Mkm5OFA1PjN:L3G+
A673	NFX3XVhyUFSVIHHzd4F6				MXPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSTZ5MzDj[Yxtew>?	MlnyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
DAOY	M1nRbZFJXFNiYYPzZZk>				MWDxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhTEGRWTDj[Yxtew>?	MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
RD	M2DiXJFJXFNiYYPzZZk>				MVHxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWkRiY3XscJM>	MkSzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-SH	Mk\xdWhVWyCjc4PhfS=>				NYHISGIxeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPLMW4uW0hiY3XscJM>	NEHueHA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
MG 63 (6-TG R)	Ml73dWhVWyCjc4PhfS=>				NW\sUW84eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF3HJFY{KCh4LWTHJHIqKGOnbHzz	MmH1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
NB1643	NILkfmpyUFSVIHHzd4F6				NYDWc4RXeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF7CNVY1OyClZXzsdy=>	M4XYfVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
OHS-50	NYXaXJl[eUiWUzDhd5NigQ>?				MWLxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhV0iVLUWwJINmdGy\|	NYfoOY9PRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
A673	NH7CfYNyUFSVIHHzd4F6				MUHxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDBOlc{KGOnbHzzLS=>	M2jiWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
U-2 OS	NIXwPFRyUFSVIHHzd4F6				NX\VdoI1eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhXS1{IF;TJINmdGy\|	NUPM[mpvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh41	MorzdWhVWyCjc4PhfS=>				MX;xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDSbFQyKGOnbHzz	MlraQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SJ-GBM2	MYPxTHRUKGG\|c3H5				M1HaZZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSj3HRm0zKGOnbHzz	NELaOJE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SK-N-MC	NVf2NZJJeUiWUzDhd5NigQ>?				Mo\kdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFONLV6tUWMh[2WubIO=	M1fBfVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
LAN-5	NGDY[4NyUFSVIHHzd4F6				NUfv[JJweUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFzBUk02KGOnbHzz	MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-MC	NWLGUnZSeUiWUzDhd5NigQ>?				NXLL[IFkeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhW0tvTj3NR{Bk\Wyucx?=	M2Kxe\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
TC32	NETyR3ZyUFSVIHHzd4F6				MknCdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgWGM{OiClZXzsdy=>	M1zBdVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	p-ERK / p-CRAF; PubMed: 22448344 Cancer Discov BRAF mutant cell lines from (A) were treated with 3µM vemurafenib for the indicated times, and lysates were probed with the indicated antibodies. p-MEK(S217/221) / pAKT(T308) / p-AKT(S473) / p-P70 S6K(T389) / p-S6(Ser235-236) / P-4EB-P1; PubMed: 22194965 PLoS One Western blot analysis of phosphorylated and the total amount of key proteins in the MAPK and PI3K/AKT pathways after 24 hours of exposure to the solvent (DMSO), or various concentrations of the BRAF inhibitor vemurafenib. The vemurafenib-sensitive M238 and M229 cell lines and the vemurafenib in vitro acquired resistant sublines M238-AR2 and M229-AR9 were cultured at different concentrations of vemurafenib. p70 and p-p70 S6K in this figure are referred to S6K1 and phosphorylated form of S6K1, respectively. Bax / Bcl2 / Bcl-xl / BIM / Mcl1; PubMed: 28382170 Theranostics Change of Bcl-2 family proteins following Vemurafenib treatment for 24 h.	22448344 22194965 28382170
Growth inhibition assay	Cell viability; PubMed: 29179510 Oncotarget At different time point of the experiment (expressed in days), sensitivity to vemurafenib was evaluated in the different A375 cell lines. Cells were treated with 10-fold dilution series (1 nM to 10 uM) of Vemurafenib and cell viability was assessed after 72 h by Crystal violet staining. Cell viability results are expressed in fold vs. the untreated cells.	29179510
Immunofluorescence	uPAR / α5-β1; PubMed: 30611716 EBioMedicine Representative images of confocal microscopy of companion M6R treated cultures stained with specific anti-uPAR (red), α5β1 (green) and DAPI (blue). Experiments have been performed three times in triplicate with analogous results. The co-localization score is quantified by image J andreported within each picture as Manders' coefficient (MC). The shown pictures are representative of 20 different pictures for each experimental condition. Scale bar = 20 μm. p-Akt(Thr308); PubMed: 27293997 Am J Cancer Res Vemurafenib reduced phosphorylated Akt in HUVEC. Cells were treated with vemurafenib for 4 h and processed for immunofluorescence staining with antibodies against p-AktThr308. Cell nuclei were stained with DAPI. Scale bar represents 50 μm.	30611716 27293997

In vivo

In B-RAF^V600E-mutant mice xenograft models, PLX4032 (6 mg/kg–20 mg/kg) inhibits tumor growth. ^[1] In mice xenograft models of LOX, Colo829, and A375 cells, PLX4032 (12.5 mg/kg–100 mg/kg) inhibits tumor growth and prolongs mice survival. ^[2]

Protocol

Kinase Assay: ^[1]	- Collapse RAF kinase activity measurements: The kinase activities of wild-type RAF and mutants are determined by measuring phosphorylation of biotinylated-BAD protein. For each enzyme (0.01 ng), 20 μL reactions are carried out in 20 mM Hepes (pH 7.0), 10 mM MgCl₂, 1 mM DTT, 0.01% (v/v) Tween-20, 50 nM biotin-BAD protein, and 1 mM ATP at room temperature. Reactions are stopped at 5 min with 5 μL of a solution containing 20 mM Hepes (pH 7.0), 200 mM NaCl, 80 mM EDTA, 0.3% (w/v) bovine serum albumin (BSA). The stop solution also includes phospho-BAD (Ser112) antibody, streptavidin-coated donor beads, and protein A acceptor beads. The antibody and beads are pre-incubated in stop solution in the dark at room temperature for 30 min. The final dilution of antibody is 1/2000 and the final concentration of each bead is 10 μg/mL. The assay plates are incubated at room temperature for one hour and then are read on a PerkinElmer AlphaQuest reader. Mutant activities are the average of two different batches of purified protein assayed in duplicate in three different experiments.
Cell Research: ^[2]	- Collapse Cell lines: MALME-3M, Colo829, Colo38, A375, SK-MEL28, and A2058 cells Concentrations: 0–10 μM , dissolved in DMSO Incubation Time: 5 days Method: Cellular proliferation is evaluated by MTT assay. Briefly, cells are plated in 96-well microtiter plates at a density of 1000 to 5000 cells per well in a volume of 180 μL. PLX4032 is prepared at 10 times the final assay concentration in media containing 1% DMSO. Twenty-four hours after cell plating, 20 μL of the appropriate dilution of PLX4032 are added to plates in duplicate. The plates are assayed for proliferation 6 days after the cells are plated. Percent inhibition is calculated and the IC50 is determined from the regression of a plot of the logarithm of the concentration versus percent inhibition. (Only for Reference)
Animal Research: ^[2]	- Collapse Animal Models: Mice (athymic nude) xenograft models of LOX, Colo829, and A375 cells Dosages: 12.5 mg/kg–100 mg/kg Administration: Oral gavage twice daily (Only for Reference)

References

- Collapse

Solubility (25°C)

In vitro	DMSO	97 mg/mL (197.99 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 4% DMSO+30% PEG 300+5% Tween 80+ddH2O (suspension) 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 Vemurafenib (PLX4032) SDF

Molecular Weight	489.92
Formula	C₂₃H₁₈ClF₂N₃O₃S
CAS No.	918504-65-1
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	RG7204
Smiles	CCCS(=O)(=O)NC1=C(C(=C(C=C1)F)C(=O)C2=CNC3=C2C=C(C=N3)C4=CC=C(C=C4)Cl)F

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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.
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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2020-01-06)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT03410875	Recruiting	Drug: Vemurafenib\|Drug: Obinutuzumab	Hairy Cell Leukemia\|Leukemia\|Leukemia Hairy Cell	Memorial Sloan Kettering Cancer Center\|Dana-Farber Cancer Institute\|Yale University	February 9 2018	Phase 2
NCT03013491	Active not recruiting	Drug: CX-072\|Drug: ipilimumab\|Drug: vemurafenib	Solid Tumor\|Lymphoma	CytomX Therapeutics	January 2017	Phase 1\|Phase 2
NCT02441465	Completed	Drug: Vemurafenib\|Drug: 14C-Labeled Vemurafenib	Malignant Melanoma Cancer	Hoffmann-La Roche	August 13 2015	Phase 1
NCT02427893	Withdrawn	Drug: Cobimetinib\|Drug: Vemurafenib	Melanoma	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins\|Genentech Inc.	August 2015	Phase 3

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

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

Frequently Asked Questions

Question 1:
How about the half-life of Vemurafenib(S1267)?
Answer:
It was reported that the half-life of the compound is 57 hours.
Question 2:
The vemurafenib power, when prepared in 4% DMSO/30% PEG 300/5% Tween 80/ddH2O solutions, form a pellet down the tube?
Answer:
When prepare this kind of vehicle, please dissolve the drug in DMSO clearly first. If it dissolves not readily, please sonicate and warm in the water bath at about 45 degree. Then add PEG and Tween. After they mixed homogeneously, then dilute with water.

Raf Signaling Pathway Map

Raf Inhibitors with Unique Features

Selective Raf Inhibitors

SB590885 : B-Raf-selective, K_i=0.16 nM.
Selective Raf Inhibitors

ZM 336372 : C-Raf-selective, IC50=70 nM.
FDA-approved Raf Inhibitor

Sorafenib Tosylate : Approved by FDA for advanced renal cancer.
Newest Raf Inhibitor

TAK-632 ^New : Potent pan-Raf inhibitor with IC50 of 8.3 nM and 1.4 nM for B-Raf(wt) and C-Raf, respectively, showing less or no inhibition against other tested kinases.

Related Raf Products

LY3009120 ^New

LY03009120 is a potent pan-Raf inhibitor with IC50 of 44 nM, 31-47 nM, and 42 nM for A-raf, B-Raf, and C-Raf in A375 cells, respectively. LY03009120 induces autophagy. Phase 1.
Ravoxertinib (GDC-0994) ^New

Ravoxertinib (GDC-0994) is a potent, orally available and highly selective ERK1/2 inhibitor with IC50 of 1.1 nM and 0.3 nM, respectively. Phase 1.
Ulixertinib (BVD-523) ^New

Ulixertinib (BVD-523, VRT752271) is a potent and reversible ERK1/ERK2 inhibitor with IC50 of <0.3 nM for ERK2. Phase 1.
Dabrafenib (GSK2118436)

Dabrafenib (GSK2118436) is a mutant BRAFV600 specific inhibitor with IC50 of 0.7 nM in cell-free assays, with 7- and 9-fold less potency against B-Raf(wt) and c-Raf, respectively.
Sorafenib

Sorafenib (BAY 43-9006) is a multikinase inhibitor of Raf-1 and B-Raf with IC50 of 6 nM and 22 nM in cell-free assays, respectively. Sorafenib inhibits VEGFR-2, VEGFR-3, PDGFR-β, Flt-3 and c-KIT with IC50 of 90 nM, 20 nM, 57 nM, 59 nM and 68 nM, respectively. Sorafenib induces autophagy and apoptosis and activates ferroptosis with anti-tumor activity.
Sorafenib Tosylate

Sorafenib Tosylate (Bay 43-9006) is a multikinase inhibitor of Raf-1 and B-Raf with IC50 of 6 nM and 22 nM in cell-free assays, respectively. Sorafenib Tosylate inhibits VEGFR-2, VEGFR-3, PDGFR-β, Flt-3 and c-KIT with IC50 of 90 nM, 20 nM, 57 nM, 59 nM and 68 nM, respectively. Sorafenib Tosylate induces autophagy and apoptosis and activates ferroptosis with anti-tumor activity.
PLX-4720

PLX4720 is a potent and selective inhibitor of B-Raf^V600E with IC50 of 13 nM in a cell-free assay, equally potent to c-Raf-1(Y340D and Y341D mutations), 10-fold selectivity for B-RafV600E than wild-type B-Raf.
TAK-632

TAK-632 is a potent pan-Raf inhibitor with IC50 of 8.3 nM and 1.4 nM for B-Raf(wt) and C-Raf in cell-free assays, respectively, showing less or no inhibition against other tested kinases.
GDC-0879

GDC-0879 (AR-00341677) is a novel, potent, and selective B-Raf inhibitor with IC50 of 0.13 nM in A375 and Colo205 cells with activity against c-Raf as well; no inhibition known to other protein kinases.
GW5074

GW5074 is a potent and selective c-Raf inhibitor with IC50 of 9 nM, no effect on the activities of JNK1/2/3, MEK1, MKK6/7, CDK1/2, c-Src, p38 MAP, VEGFR2 or c-Fms is noted. GW5074 inhibits LK-induced apoptosis.

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Vemurafenib (PLX4032)