Afatinib (BIBW2992)

Name: Afatinib (BIBW2992)
Brand: Selleck Chemicals
SKU: S1011
Rating: 5 (291 reviews)

For research use only.

Catalog No.S1011

291 publications

CAS No. 850140-72-6

Afatinib (BIBW2992) inhibits EGFR/ErbB irreversibly in vitro with IC50 of 0.5, 0.4, 10, 14, 1 nM for EGFR^wt, EGFR^L858R, EGFR^L858R/T790M ErbB2 (HER2) and ErbB4 (HER4), respectively. Afatinib induces autophagy.

Selleck's Afatinib (BIBW2992) has been cited by 291 publications

Cancer Cell, 2021, S1535-6108(20)30609-7

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Nat Cell Biol, 2021, 23(4):377-390

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Nature, 2020, 584(7822):608-613

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Nature, 2019, 571(7763):127-131

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Nat Med, 2019, 25(1):111-118

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Cancer Discov, 2019, 9(7):926-943

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

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

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Cancer Cell, 2019, 10.1016/j.ccell.2019.09.001

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Nat Med, 2018, 24(7):968-977

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Nat Med, 2018, 24(5):638-646

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Cell, 2018, 172(1-2):373-386

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Nat Methods, 2018, 15(8):631-639

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Nat Med, 2017, 23(10):1167-1175

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Nature, 2016, 30;534(7609):647-51.

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Cancer Discov, 2015, 5(7):713-22

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Cancer Discov, 2013, 3(2):168-81

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Clin Cancer Res, 2021, 27(9):2533-2548

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Genome Med, 2021, 13(1):142

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Cancer Res, 2021, canres.2276.2020

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Cell Rep, 2021, 35(8):109181

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Mol Cancer, 2021, 20(1):17

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EBioMedicine, 2021, 64:103220

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Cancer Lett, 2021, S0304-3835(21)00309-8

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Cancers (Basel), 2021, 13(14)3635

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Cell Death Dis, 2021, 12(8):728

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Arch Toxicol, 2021, 10.1007/s00204-021-03147-4

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Cells, 2021, 10(7)1647

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Pharmacol Res, 2021, 170:105701

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Transl Lung Cancer Res, 2021, 10(8):3659-3670

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Cell Oncol (Dordr), 2021, 10.1007/s13402-021-00632-x

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Front Oncol, 2021, 11:665045

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Front Oncol, 2021, 11:711043

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Biochem Pharmacol, 2021, 190:114642

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Int J Mol Sci, 2021, 22(2)E752

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Int J Mol Sci, 2021, 22(8)4005

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Drug Metab Dispos, 2021, 49(1):53-61

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Cancer Res Treat, 2021, 10.4143/crt.2021.385

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Transl Oncol, 2021, 14(8):101110

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Onco Targets Ther, 2021, 14:3813-3820

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Thorac Cancer, 2021, 10.1111/1759-7714.13931

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Jpn J Clin Oncol, 2021, hyab048

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Oncol Lett, 2021, 21(5):418

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Hum Cell, 2021, 10.1007/s13577-021-00579-z

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Lung Cancer, 2021, 154:84-91

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EBioMedicine, 2021, 64:103220

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Nat Nanotechnol, 2021, 10.1038/s41565-021-00872-w

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PLoS Pathog, 2021, 17(2):e1009303

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Mol Psychiatry, 2021, 10.1038/s41380-021-01137-7

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Toxicol Lett, 2021, S0378-4274(21)00043-6

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Acta Neuropathol, 2020, 17

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Cell Res, 2020, 10.1038/s41422-020-00409-1

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Nat Commun, 2020, 25;11(1):1556

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Clin Cancer Res, 2020, clincanres.3555.2020

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Clin Cancer Res, 2020, 10.1158/1078-0432

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Genome Med, 2020, 18;12(1):17

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Redox Biol, 2020, 38:101780

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Oncogene, 2020, 10.1038/s41388-020-01564-w

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Oncogene, 2020, 39(20):3997-4013

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Cancer Lett, 2020, 476:23-33

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J Invest Dermatol, 2020, 3 pii: S0022-202X(20)31407-X

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Cancers (Basel), 2020, 13;12(2) pii: E436

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Cell Death Dis, 2020, 11(10):882

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Cell Death Dis, 2020, 2;11(1):6

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Signal Transduct Target Ther, 2020, 5(1):214

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Cancer Discov, 2020, 10(5):674-687

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Oral Oncol, 2020, 112:105074

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J Virol, 2020, JVI.02001-20

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Antimicrob Agents Chemother, 2020, 1;AAC.00341-20

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Sci Rep, 2020, 10(1):17768

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Cancer Cell Int, 2020, 19;20:58

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BMC Cancer, 2020, 20(1):129

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J Cancer Res Clin Oncol, 2020, 146(3):605-619

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Am J Transl Res, 2020, 15;12(3):847-856 eCollection 2020

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Cancer Res Treat, 2020, 10.4143/crt.2020.585

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Toxicol In Vitro, 2020, 104928

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Oncol Rep, 2020, 44(6):2581-2594

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Hum Cell, 2020, 10.1007/s13577-020-00420-z

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Hum Cell, 2020, 10.1007/s13577-020-00425-8

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Anticancer Res, 2020, 40(4):1867-1874

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Korean J Parasitol, 2020, 58(3):249-255

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Radiat Oncol, 2020, 15(1):58

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Mol Cancer Res, 2020, 18(4):537-548

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BMC Pharmacol Toxicol, 2020, 21(1):61

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NPJ Breast Cancer, 2020, 6:30

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Physiol Rep, 2020, 8(13):e14490

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Genome Biol, 2020, 21(1):181

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J Cancer, 2020, 11(1):241-250

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J Cell Physiol, 2020, 10.1002/jcp.30172

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Viruses, 2020, 12(11)E1294

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Rapid Commun Mass Spectrom, 2020, 10.1002/rcm.8955

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Cancer Cell Int, 2020, 20:376

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Neurooncol Adv, 2020, Dec;2(1):vdaa020

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Sci Rep, 2020, 10(1):12982

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Nat Commun, 2019, 10(1):2532

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Nano Lett, 2019, 19(10):7526-7533

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Clin Cancer Res, 2019, 10.1158/1078-0432

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Int J Cancer, 2019, 10.1002/ijc.32487

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Oncogene, 2019, 38(30):5890-5904

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Cancer Lett, 2019, 466:23-34

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J Exp Clin Cancer Res, 2019, 38(1):282

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J Exp Clin Cancer Res, 2019, 38(1):266

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Cancers (Basel), 2019, 11(1)

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Cancers (Basel), 2019, 11(6)

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Cell Death Dis, 2019, 10(9):663

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Br J Cancer, 2019, 121(10):846-856

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Cancers (Basel), 2019, 11(2)

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Acta Pharm Sin B, 2019, 9(6):1193-1203

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Cells, 2019, 8(12)

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Oncoimmunology, 2019,

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Mol Cancer Ther, 2019, 18(4):733-742

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Mol Cancer Ther, 2019, 18(5):920-928

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J Cancer, 2019, 10(9):2063-2073

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Am J Cancer Res, 2019, 9(6):1282-1292

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Oncogenesis, 2019, 8(10):54

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Mol Cancer Res, 2019, 17(11):2233-2243

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Gynecol Oncol, 2019, 153(1):158-164

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J Cell Physiol, 2019, 10.1002/jcp.28881

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Cancer Sci, 2019, 110(11):3584-3594

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Sci Rep, 2019,

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Clin Lung Cancer, 2019, 20(3):167-177

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J Biol Chem, 2019, 294(12):4488-4497

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Mol Pharmacol, 2019, 95(5):528-536

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Respir Res, 2019, 20(1-:270

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Acta Pharmacol Sin, 2019, 10.1038/s41401-019-0248-2

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Front Physiol, 2019, 10:189

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Cancer Res Treat, 2019, 51(3):951-962

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Transl Oncol, 2019, 12(6):852-858

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Oncol Rep, 2019, 41(2):1059-1066

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Clin Otolaryngol, 2019, 10.1111/coa.13434

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Mol Med Rep, 2019, 20(4):3317-3325

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Pharmaceuticals (Basel), 2019, 12(4)

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J Thorac Oncol, 2019, 14(9):1556-1566

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JCI Insight, 2019, 4(4)

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Cell Mol Gastroenterol Hepatol, 2019, 8(1):37-60

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Oncotarget, 2019, 10(14):1440-1457

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JCI Insight, 2019, 4(21)

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Nat Struct Mol Biol, 2018, 25(6):454-462

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EMBO Mol Med, 2018, 10(9)

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EMBO Mol Med, 2018, 10(9):e8746

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Clin Cancer Res, 2018, 24(11):2594-2604

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Proc Natl Acad Sci U S A, 2018, 115(26):E6030-E6038

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Genes Dev, 2018, 32(17-18):1201-1214

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Cancer Immunol Res, 2018, 6(12):1511-1523

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Clin Cancer Res, 2018, 15;24(6):1436-1447

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Theranostics, 2018, 8(12):3176-3188

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Cancer Res, 2018, 78(24):6866-6880

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

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Sci Signal, 2018, 11(549)

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EBioMedicine, 2018, 29:112-127

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Cancers (Basel), 2018, 10(6)

PubMed: 29925812 ( click the link to review the publication )

Cell Death Dis, 2018,

PubMed: 29880898 ( click the link to review the publication )

Cancer Discov, 2018, 8(9):1087-1095

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Mol Cancer Ther, 2018, 17(8):1648-1658

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Mol Cancer Ther, 2018, 17(10):2144-2155

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Mol Cancer Ther, 2018, 17(9):2024-2033

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Mol Oncol, 2018, 12(6):830-854

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Mol Oncol, 2018, 12(4):441-462

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Cancer Sci, 2018, 109(11):3657-3661

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Mol Cancer Res, 2018, 16(11):1773-1784

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Lung Cancer, 2018, 126:72-79

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Front Oncol, 2018, 8:432

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Sci Rep, 2018, 8(1):18043

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J Biol Chem, 2018, 293(42):16518-16527

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Am J Cancer Res, 2018, 8(8):1541-1550

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Ann Thorac Surg, 2018, 105(2):363-370

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Int J Oncol, 2018, 53(4):1544-1556

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Invest New Drugs, 2018, 36(6):999-1005

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Transl Oncol, 2018, 11(6):1406-1418

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Biosci Rep, 2018, 38(6)

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Onco Targets Ther, 2018, 11:8201-8209

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J Craniomaxillofac Surg, 2018, 46(3):492-497

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Mol Cancer Ther, 2018, 17(8):1648-1658

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Bladder Cancer, 2018, 4(1):77-90

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J Am Chem Soc, 2018, 140(40):12785-12797

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Sci Rep, 2018, 8(1):14896

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Oncotarget, 2018, 9(9):8560-8572

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Nat Commun, 2017, 8(1):410

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Nat Commun, 2017, 8(1):823

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Nat Commun, 2017, 8:13897

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Theranostics, 2017, 7(4):974-986

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Elife, 2017, 10.7554/eLife.25946

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Oncogene, 2017, 36(47):6581-6591

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Oncogene, 2017, 36(13):1873-1886

PubMed: 27694893 ( click the link to review the publication )

Oncogene, 2017, 36(48):6691-6700

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Cell Death Dis, 2017, 8(5):e2773

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Arch Toxicol, 2017, 91(8):2921-2938

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Mol Cancer Ther, 2017,

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Neoplasia, 2017, 19(12):1012-1021

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Sci Rep, 2017, 7:44206

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Sci Rep, 2017, 7:44089

PubMed: 28276478 ( click the link to review the publication )

Cancer Prev Res, 2017, 10(1):76-88

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Toxicol Appl Pharmacol, 2017, 335:16-27

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BMC Cancer, 2017,

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Biochem Biophys Res Commun, 2017, 486(4):1027-1033

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Biochem Biophys Res Commun, 2017, 491(3):656-661

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SLAS Discov, 2017, 22(7):915-922

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Oncol Lett, 2017, 14(4):4349-4354

PubMed: 28959367 ( click the link to review the publication )

Oncotarget, 2017, 8(3):4277-4288

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Oncotarget, 2017, 8(14):22414-22432

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Oncotarget, 2017,

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Oncotarget, 2017, 8(29):47305-47316

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Oncotarget, 2017, 8(38):63901-63910

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Oncotarget, 2017, 8(35):58771-58780

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BMB Rep, 2017, 50(3):150-155

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Oncotarget, 2017,

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Elife, 2017, 6

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Oncotarget, 2017,

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Gut, 2016, 1296-305

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Genome Biol, 2016, 17:80

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Elife, 2016, 10.7554/eLife.18489

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Expert Opin Drug Deliv, 2016, 13(1):133-41

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PLoS Genet, 2016, 12(9):e1006279

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Mol Cancer Ther, 2016,

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Mol Cancer Ther, 2016,

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Cancer Sci, 2016, 107(8):1134-40

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Mol Pharm, 2016, 13(6):2117-25

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Am J Cancer Res, 2016, 6(8):1708-19

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Stem Cells Int, 2016, 2016:9601493

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PLoS One, 2016, 11(5):e0155230

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PLoS One, 2016, 11(1):e0146311

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Mol Med Rep, 2016, 13(3):2338-44

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Oncotarget, 2016, 7(28):42859-42872

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Cancer Immunol Res, 2016,

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Oncotarget, 2016, 7(36):58038-58050

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Cancer Immunol Res, 2016,

PubMed: 27680026 ( click the link to review the publication )

Oncotarget, 2016, 7(4):3847-56

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Oncotarget, 2016, 7(26):40398-40417

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Oncotarget, 2016, 7(50):83424-83436

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Oncotarget, 2016,

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Gut, 2015, 10.1136/gutjnl-2014-309026

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Nat Commun, 2015, 6:8481

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J Thorac Oncol, 2015, 10(1):93-101

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Clin Cancer Res, 2015, 10.1158/1078-0432.CCR-14-2789

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Clin Cancer Res, 2015, 10.1158/1078-0432.CCR-15-0560

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Clin Cancer Res, 2015, 21(20):4597-606

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J Cell Biol, 2015, 211(2):391-405

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Cell Rep, 2015, 11(1):98-110

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Int J Cancer, 2015, 136(11):2717-29

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Purity & Quality Control

Choose Selective EGFR Inhibitors

Biological Activity

Description

Targets

EGFR (L858R) ^[1] (Cell-free assay)	EGFR (wt) ^[1] (Cell-free assay)	ErbB4 ^[2] (Cell-free assay)	EGFR (L858R/T790M) ^[1] (Cell-free assay)	HER2 ^[1] (Cell-free assay)
0.4 nM	0.5 nM	1 nM	10 nM	14 nM

In vitro

BIBW2992 shows potent activity against both wild-type and mutant forms of EGFR and HER2. It is similar to Gefitinib in potency against L858R EGFR, but about 100-fold more active against the Gefitinib resistant L858R-T790M EGFR double mutant. BIBW2992 exhibits potent effects on both EGFR and HER2 phosphorylation in vivo. It compares favorably to reference compounds (such as Lapatinib et al.) in all cell types tested, such as human epidermoid carcinoma cell line A431 expressing wt EGFR, murine NIH-3T3 cells transfected with wt HER2, as well as breast cancer cell line BT-474 and gastric cancer cell line NCI-N87, which express endogenous HER2. ^[1]

Cell Data

Cell Lines	Assay Type	Activity Description	PMID
HDLM-2	M4HFT2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M{fme2lEPTB;MD6wNFU4OiEQvF2=	NV7GTItiRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
KASUMI-1	NEfFUYRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NHXTe5BKSzVyPUCuNFA6OTFizszN	NHPpbWI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTd\|NkW1M{c,W0GQR1XSQE9iRg>?
HCC2218	NXPGXJhIT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MVjJR\|UxRTBwMEC5PFch\|ryP	MojOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
KARPAS-45	NIW3UWxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MnuzTWM2OD1yLkCxOlcyKM7:TR?=	NHftR2k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTd\|NkW1M{c,W0GQR1XSQE9iRg>?
HSC-4	NYjnSFNLT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NHfyeWNKSzVyPUCuNFE4PDhizszN	NH:0SYo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTd\|NkW1M{c,W0GQR1XSQE9iRg>?
CHL-1	NY\sTZBCT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MYXJR\|UxRTBwMEG4N\|kh\|ryP	MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
KY821	NGnKfpJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MljrTWM2OD1yLkCyNFYh\|ryP	NVXzWWR7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
NCI-N87	MmTKS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MV\JR\|UxRTBwMEK3O\|Mh\|ryP	NVLwdIdRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
DOK	MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M3LHVWlEPTB;MD6wN\|E6PCEQvF2=	MkXhQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
DSH1	Mlm3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MkXxTWM2OD1yLkCzN\|E1KM7:TR?=	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
MDA-MB-175-VII	NXnPfHpUT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MUHJR\|UxRTBwMEO0NVYh\|ryP	MmnBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
NCI-H2170	NEjI[5VIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MYXJR\|UxRTBwMEO3Nlgh\|ryP	NUH2O4pQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
BT-474	MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M2jSTGlEPTB;MD6wOFk5PiEQvF2=	NX\iRXBtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
EFO-27	M1TUfWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NVPk[HRZUUN3ME2wMlA2OTh{IN88US=>	NG\uS4M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTd\|NkW1M{c,W0GQR1XSQE9iRg>?
NCI-H720	NGC2Ro5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MYLJR\|UxRTBwMEWzNlUh\|ryP	MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
PC-14	NFzOTlNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MYjJR\|UxRTBwMEW2Olgh\|ryP	NVTwSpNmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
EC-GI-10	NXjJZZlwT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MmLaTWM2OD1yLkC1PVEzKM7:TR?=	NYPGc5N2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
KYSE-450	NXvuS4ZVT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MXfJR\|UxRTBwMEW5O\|gh\|ryP	NWq2U3BERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
BPH-1	NWrOfmp[T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NHHBVIxKSzVyPUCuNFU6QDhizszN	NVi5OXVZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
NCI-H292	MlTrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MkjtTWM2OD1yLkC2NFkh\|ryP	NH\Zbm49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTd\|NkW1M{c,W0GQR1XSQE9iRg>?
H9	MmD2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MVnJR\|UxRTBwMEexN\|Ih\|ryP	M2DIT\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK\|5USU6JRWK8M4E,
NCI-H526	NX;DOmc3T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MkDKTWM2OD1yLkC3PFI{KM7:TR?=	M4LGWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK\|5USU6JRWK8M4E,
NCI-H1623	MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NV3ZOG1VUUN3ME2wMlA5ODJ3IN88US=>	MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
KYSE-140	NXPvVIRzT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	Mlj2TWM2OD1yLkC4N\|Mh\|ryP	NVztNpdSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
Ca9-22	NHu3N4dIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	Mom5TWM2OD1yLkC4N\|U{KM7:TR?=	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
AU565	MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M4\r[2lEPTB;MD6wPFUxPCEQvF2=	NXr3NFR7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
ZR-75-30	M2q4Wmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M3TneGlEPTB;MD6wPVU1PSEQvF2=	NFO0cIY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTd\|NkW1M{c,W0GQR1XSQE9iRg>?
NCI-H1770	NWHWdGE5T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NEnJW49KSzVyPUCuNVAzQCEQvF2=	MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
LB2241-RCC	Mof1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M3\YS2lEPTB;MD6xNFg5PCEQvF2=	NEnHPZo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTd\|NkW1M{c,W0GQR1XSQE9iRg>?
CAL-39	M4jTWGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MoDxTWM2OD1yLkGxO\|kzKM7:TR?=	NVz3dIN5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
UACC-893	M1\Ve2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NIexO4xKSzVyPUCuNVE5QDVizszN	NGn6RmE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTd\|NkW1M{c,W0GQR1XSQE9iRg>?
LU-65	NWLjUpg6T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MWLJR\|UxRTBwMUK2N\|Mh\|ryP	M1PlVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK\|5USU6JRWK8M4E,
HN	M1nJSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MmnQTWM2OD1yLkGzNFc4KM7:TR?=	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
TI-73	MlnTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NYfGNZV1UUN3ME2wMlE1PzF3IN88US=>	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
KU812	M17WOmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NYnRZWJ5UUN3ME2wMlE2PDV4IN88US=>	MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
SW13	NEPQVWJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NGj6V2FKSzVyPUCuNVYzOTZizszN	MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
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HCC70	MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NIHLeXdKSzVyPUCuOVc3PjFizszN	NUTicJRPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
NCI-H1838	NWfScoVHT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NV\UVWVUUUN3ME2wMlYxOjl7IN88US=>	NV33cJJvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
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NCI-H1048	NILkU5RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M{H3cWlEPTB;Mj60PVE2QCEQvF2=	M2jTbVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK\|5USU6JRWK8M4E,
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NCI-H441	NIHi[4RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MonNTWM2OD1\|LkW5PFQyKM7:TR?=	M2jGeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK\|5USU6JRWK8M4E,
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NCI-H28	NX21ZmMzT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MknlTWM2OD15LkG2OFA2KM7:TR?=	NVjzZmY6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
MN-60	MnPTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M2jNVmlEPTB;Nz6yPFA5QSEQvF2=	Mm\SQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
RMG-I	MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NUPkU2toUUN3ME23MlM6Ojl4IN88US=>	M2n5VFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK\|5USU6JRWK8M4E,
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DB	M{fre2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NX[5eI1MUUN3ME23MlYyODB3IN88US=>	M17DdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK\|5USU6JRWK8M4E,
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HEL	Moj0S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NVHKU5JHUUN3ME23MlcyOjB\|IN88US=>	NVfyT25GRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
NH-12	NHL2dWFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M4X6PGlEPTB;Nz63NlgxQCEQvF2=	NGnhRXM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTd\|NkW1M{c,W0GQR1XSQE9iRg>?
LB373-MEL-D	MkHiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M1PhOGlEPTB;Nz63Olc4OSEQvF2=	MknSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
SW900	Ml\LS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NUTEWGduUUN3ME23MlgzOTJzIN88US=>	M1HLR\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK\|5USU6JRWK8M4E,
JVM-3	NFG3cIpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M4XIbWlEPTB;Nz64PVU6QSEQvF2=	NYj6ZpR7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
OAW-28	MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NUHLbFVtUUN3ME23Mlk1PTd6IN88US=>	MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
KURAMOCHI	MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MW\JR\|UxRTdwOUS4NVEh\|ryP	MnqxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
BE-13	NWDLZ2NRT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MVrJR\|UxRTdwOUixNVIh\|ryP	NFLkTJI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTd\|NkW1M{c,W0GQR1XSQE9iRg>?
VMRC-RCZ	NGPFeGNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M{[5NmlEPTB;OD6wNVY6PyEQvF2=	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
NCI-H727	M{ftXmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MUfJR\|UxRThwMUC0NkDPxE1?	MoHMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
SW1710	MlvvS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M1S4e2lEPTB;OD6xPFUyPSEQvF2=	MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
D-502MG	MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M{fMTmlEPTB;OD6yPVI5OiEQvF2=	NEmzfnI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTd\|NkW1M{c,W0GQR1XSQE9iRg>?
NCI-H1993	M1;GUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NI\6epBKSzVyPUiuN\|M3OzFizszN	MlS3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
SCC-4	MW\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MWHJR\|UxRThwNESwOVkh\|ryP	NXTTOnQ5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
HAL-01	MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NGDtNWpKSzVyPUiuOVE6OSEQvF2=	M1\RNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK\|5USU6JRWK8M4E,
GT3TKB	MlPCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MUjJR\|UxRThwNke5OlQh\|ryP	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
SK-OV-3	MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MnLyTWM2OD16LkexN\|I6KM7:TR?=	NVz5[pBQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
COLO-829	MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MWrJR\|UxRThwOEC5O\|Yh\|ryP	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
OCI-AML2	MmDES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MmG4TWM2OD16Lkm1OFgyKM7:TR?=	M3f4W\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK\|5USU6JRWK8M4E,
OS-RC-2	MkmwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M4HSd2lEPTB;OT6wNlE6KM7:TR?=	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
BFTC-909	Ml\HS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M4C0WGlEPTB;OT6wOlc6QSEQvF2=	MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
EW-11	MoLOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M{\6c2lEPTB;OT6xO\|Y2OyEQvF2=	Mk\jQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
HCE-4	MoTWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MmnmTWM2OD17LkKxOVU5KM7:TR?=	M13LO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK\|5USU6JRWK8M4E,
BALL-1	MmjoS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M37ZUWlEPTB;OT6yNVkxPyEQvF2=	NInp[pA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTd\|NkW1M{c,W0GQR1XSQE9iRg>?
SF539	M4rrdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M16y[WlEPTB;OT6yN\|U3OiEQvF2=	M3voRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK\|5USU6JRWK8M4E,
CAMA-1	M3LL[Gdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M1q5UmlEPTB;OT6yPFEzQCEQvF2=	MmjEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
C32	NHLh[2FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MnjMTWM2OD17LkOzNFY1KM7:TR?=	NIjBPZo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTd\|NkW1M{c,W0GQR1XSQE9iRg>?
NCI-H1703	MkfPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	Mlm2TWM2OD17LkO0N\|c2KM7:TR?=	NVfVSoNERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
NCI-H1650	MXjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NVq0NVlbUUN3ME25MlYxQTR4IN88US=>	NWK0W483RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
NCI-H1563	M{SxcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NVPPXoRmUUN3ME25Mlc3ODNzIN88US=>	NXPhdoNmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
CAL-85-1	NYrOSIE6T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	M3zM[WlEPTB;OT64O\|M5OyEQvF2=	NUHEc4M4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
UM-UC-3	NWT4PZZvT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MkHZTWM2OD17Lkm1NFMh\|ryP	NGnrb4I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTd\|NkW1M{c,W0GQR1XSQE9iRg>?
BxPC-3	MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M1PGT2lEPTB;MUCuNFk4OiEQvF2=	M1rRSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK\|5USU6JRWK8M4E,
MHH-PREB-1	NWLm[4NDT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MnfCTWM2OD1zMD6xPVk6KM7:TR?=	NFfuO2Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTd\|NkW1M{c,W0GQR1XSQE9iRg>?
DEL	MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NYfuVmozUUN3ME2xNE4{QTR4IN88US=>	MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxNVc{PjV3Lze+V2FPT0WUPD;hQi=>
HuCCT1	NFXyfWxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MoLDTWM2OD1zMD62NFM{KM7:TR?=	Mn;kQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
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TGBC11TKB	NEPyW21Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NH;Qc\|FKSzVyPUS3MlE4PzdizszN	Mn;pQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
HD-MY-Z	MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NGfCdVZKSzVyPUS4Mlc5PiEQvF2=	M3LrNFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFEyPzN4NUWvK\|5USU6JRWK8M4E,
NCI-H226	MmnuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MorYTWM2OD12OT63O\|g2KM7:TR?=	NV3rS5dbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
PA-1	NVf1dYxTT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NHe0TVlKSzVyPUS5Mlg{OzVizszN	MmDQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
LB2518-MEL	NVv1cFI{T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	Mn7FTWM2OD12OT64O\|I{KM7:TR?=	MofSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVE4OzZ3NT:nQnNCVkeHUkyvZV4>
A101D	M4W5emdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NXHCU4FmUUN3ME20PU46PDJ3IN88US=>	NV\VXFJyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTF5M{[1OU8oRlODTlfFVlww[T5?
NCI-H2087	NH;EcWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M1vOfWlEPTB;NEmuPVY5OiEQvF2=	NETCOmk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyOTd\|NkW1M{c,W0GQR1XSQE9iRg>?

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	CIP2A / p-AKT / AKT / PARP; PubMed: 25537503 Oncotarget Time-dependent effects of afatinib on CIP2A, p-AKT and apoptosis-related proteins in the sensitive H358 and resistant H460 cells. Cells were exposed to 10 μM afatinib for up to 48 hours. Immunoblots were scanned and quantitated to determine the ratio of the level of CIP2A to actin. Data are mean ± SD. n = 3 for the different time intervals. p-EGFR / p-IGF1R / p-ERK / p-AKT; PubMed: 26052929 Mol Carcinog Effects of afatinib on EGFR and IGF1R Signaling Pathways. H1975 cells were treated with afatinib with various doses and cell lysates were subjected to Western blot analysis. Afatinib effectively inhibits p-EGFR and p-ERK while p-AKT was partially inhibited. IGF1R phosphorylation was increased upon afatinib treatment in H1975 cells. p-VEGFR2 / VEGFR2 / JAG1 / DLL4 / NICD1 ; PubMed: 28533486 Oncotarget HUVECs were cultured in the presence of Vatalanib (100 nM) or DBZ (10 nM) for 1 h and then treated for 15 min with rhgal-3 (37 nM) and cultured for additional 6 hrs. After this period, the total protein was isolated and the protein levels of galectin-3, NICD1, DLL4, JAG1, VEGFR2 and VEGFR2-p were assessed by Western blot. β-actin was used as a loading control.	25537503 26052929 28533486
Growth inhibition assay	Cell apoptosis; PubMed: 25537503 Oncotarget Dose-dependent effects of afatinib on apoptosis. Data are mean ± SD. n = 3 for each concentration. , p < 0.05, *, p < 0.01, vs. no afatinib. Cell viability; PubMed: 26515464 Oncotarget A. MTS assay for Ba/F3 cells harboring EGFR exon 19 deletion and L858R. The proportional cell viability is shown. B. MTS assay for Ba/F3 cells harboring EGFR exon 19 deletion+T790M and L858R+T790M. The proportional cell viability is shown. C. MTS assay for Ba/F3 cells harboring wild type EGFR. The proportional cell viability is shown. Erlotinib, afatinib, osimertinib, and rociletinib were used as EGFR-TKIs. Error bars indicate standard deviation.	25537503 26515464
Immunofluorescence	p65; PubMed: 26317651 Oncotarget Effects of different treatments on the nuclear translocation of the NF-κB subunit p65. A2780T cells were treated with 2.5 μM afatinib for 48 hours, or 10 μM PDTC for 2 hours. Subsequently, the NF-κB subunit p65 (red) was localized by immunofluorescence and a confocal microscopy. Nuclei were stained with DAPI (blue). Scale bar = 10 μM. vacuoles; PubMed: 29713246 Cancer Cell Int Autophagy activation upon treatment with Afatinib and Sorafenib was validated using immunofluorescence in order to visualize a creation of autophagosomes; ×60 magnification. DMSO treatment was used as control. Green—autophagy vacuoles; Blue—Hoechst, nuclear staining.	26317651 29713246

In vivo

Daily oral administration of BIBW2992 at 20 mg/kg for 25 days results in dramatic tumor regression with a cumulative treated/control tumor volume ratio (T/C ratio) of 2%. Reduced phosphorylation of EGFR and AKT is confirmed by immunohistochemical staining of tissue sections. Therefore, like lapatinib and neratinib, BIBW2992 is a next generation tyrosine kinase inhibitor (TKI) that inhibits human epidermal growth factor receptor 2 (Her2) and epidermal growth factor receptor (EGFR) kinases irreversibly. BIBW2992 is not only active against EGFR mutations targeted by first generation TKIs like Erlotinib or Gefitinib, but also against those insensitive to these standard therapies. ^[1]

Protocol

Kinase Assay: ^[1]	- Collapse In vitro kinase activity assays: The wild type tyrosine kinase domain of the human EGFR as well as that of the EGFR L858R/T790M double mutant are fused to Glutathione-S-transferase (GST), and extracted. Enzyme activity is then assayed in the presence of the inhibitor BIBW2992, serially diluted in 50% DMSO. A random polymer pEY (4:1) is used as substrate and biotinylated pEY (bio-pEY) is added as a tracer substrate. The kinase domain of HER2 is cloned using the baculovirus system and extracted similarly to that of EGFR kinase. Details of assays for EGFR, HER2, SRC, BIRK and VEGFR2 kinase activity are available in Supplementary information.
Cell Research: ^[1]	- Collapse Cell lines: NSCLC cells Concentrations: 0-10 μM Incubation Time: 1 hour Method: 1 × 10⁴ NSCLC cells are transferred into each well of a 96-well plate and cultured overnight in serum-free media for the EGFR phosphorylation assay. After addition of BIBW2992 on the next day, the plates are incubated at 37 °C for 1 hour. EGF-stimulation is done using 100 ng/mL for 10 min at room temperature. Cells are washed with ice cold PBS, extracted with 120 μL HEPEX buffer per well and shaken at room temperature for 1 hour. In all 2 × 10⁴ cells per well is used for the HER2 phosphorylation assay. Streptavidin precoated plates are coated with anti-EGFR-biotin at 1:100 dilution in blocking buffer and c-erb2/HER2 oncoprotein Ab-5(Clone N24)-Biotin. Cell extracts is then transferred to the antibody-coated wells and incubated at room temperature for 1 hour. Extinction is measured at 450 nm. (Only for Reference)
Animal Research: ^[1]	- Collapse Animal Models: Athymic NMRI-nu/nu female mice Dosages: 20 mg/kg Administration: Oral administration (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	97 mg/mL (199.61 mM)
	Ethanol	15 mg/mL (30.86 mM)
	Water	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 2% DMSO+30% PEG 300+5% Tween 80+ddH2O For best results, use promptly after mixing.	10mg/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 Afatinib (BIBW2992) SDF

Molecular Weight	485.94
Formula	C₂₄H₂₅ClFN₅O₃
CAS No.	850140-72-6
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CN(C)CC=CC(=O)NC1=C(C=C2C(=C1)C(=NC=N2)NC3=CC(=C(C=C3)F)Cl)OC4CCOC4

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

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

Note：1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

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

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04497584	Not yet recruiting	Drug: Afatinib + Prednisone	Advanced Squamous Non Small Cell Lung Cancer	University of Texas Southwestern Medical Center	September 1 2021	Phase 2
NCT04795245	Not yet recruiting	Drug: afatinib	Non-squamous Non-Small Cell Lung Cancer	Boehringer Ingelheim	August 31 2021	--
NCT04413201	Recruiting	Drug: Afatinib\|Drug: Osimertinib	Non-squamous NSCLC	Michael Hopp\|Boehringer Ingelheim\|Johannes Gutenberg University Mainz	September 11 2020	Phase 4
NCT04206787	Recruiting	Drug: Afatinib	Non-squamous Non-Small Cell Lung Cancer	Boehringer Ingelheim	May 20 2020	--
NCT04158947	Recruiting	Drug: Afatinib\|Drug: T-DM1	HER2-positive Breast Cancer\|Brain Metastases	xuexin he\|Second Affiliated Hospital School of Medicine Zhejiang University	May 10 2020	Phase 2

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:
What’s the recommendation about reconstitution of the compound for in vivo animal study?
Answer:
For in vivo experiment of afatinib, we recommend 0.5% methylcellulose/0.2% Tween 80 as vehicle.

EGFR Signaling Pathway Map

EGFR Inhibitors with Unique Features

Selective EGFR Inhibitor

Erlotinib HCl (OSI-744) : EGFR-selective, IC50=2 nM.
FDA-approved EGFR Inhibitor

Lapatinib : Approved by FDA for breast cancer.
Newest EGFR Inhibitor

CO-1686 (AVL-301) ^New : Irreversible, mutant-selective EGFR inhibitor with K_i of 21.5 nM and 303.3 nM for EGFRL858R/T790M and EGFRWT, respectively.

Related EGFR Products

Erlotinib (OSI-774) ^New

Erlotinib (OSI-774, CP358774, NSC 718781, Tarceva) is an EGFR inhibitor with IC50 of 2 nM, >1000-fold more sensitive for EGFR than human c-Src or v-Abl. Erlotinib induces autophagy.
Afatinib (BIBW2992) Dimaleate ^New

Afatinib (BIBW2992) Dimaleate irreversibly inhibits EGFR/HER2 including EGFR(wt), EGFR(L858R), EGFR(L858R/T790M) and HER2 with IC50 of 0.5 nM, 0.4 nM, 10 nM and 14 nM, respectively; 100-fold more active against Gefitinib-resistant L858R-T790M EGFR mutant. Afatinib (BIBW2992) Dimaleate induces autophagy.
Poziotinib (HM781-36B) ^New

Poziotinib (HM781-36B, NOV120101) is an irreversible pan-HER inhibitor with IC50 of 3.2 nM, 5.3 nM and 23.5 nM for HER1, HER2, and HER4, respectively. Poziotinib also induces apoptosis and G1 cell cycle arrest. Phase 2.
Gefitinib (ZD1839)

Gefitinib (ZD-1839, Iressa) is an EGFR inhibitor for Tyr1173, Tyr992, Tyr1173 and Tyr992 in the NR6wtEGFR and NR6W cells with IC50 of 37 nM, 37nM, 26 nM and 57 nM, respectively. Gefitinib promotes autophagy and apoptosis of lung cancer cells via blockade of the PI3K/AKT/mTOR pathway.

Features:A potent EGFR tyrosine kinase inhibitor.
Erlotinib HCl (OSI-744)

Erlotinib HCl (OSI-744, CP358774, NSC 718781) is an EGFR inhibitor with IC50 of 2 nM in cell-free assays, >1000-fold more sensitive for EGFR than human c-Src or v-Abl.
Osimertinib (AZD9291)

Osimertinib (AZD9291) is an oral, irreversible, and mutant-selective EGFR inhibitor with IC50 of 12.92, 11.44 and 493.8 nM for Exon 19 deletion EGFR, L858R/T790M EGFR, and WT EGFR in LoVo cells, respectively. Phase 3.
Lapatinib (GW-572016)

Lapatinib (GW-572016, GSK572016, GW2016), used in the form of Lapatinib Ditosylate, is a potent EGFR and ErbB2 inhibitor with IC50 of 10.8 and 9.2 nM in cell-free assays, respectively. Lapatinib induces ferroptosis and autophagic cell death.
AG-490 (Tyrphostin B42)

AG-490 (Tyrphostin B42, Zinc02557947) is an inhibitor of EGFR with IC50 of 0.1 μM in cell-free assays, 135-fold more selective for EGFR versus ErbB2, also inhibits JAK2 with no activity to Lck, Lyn, Btk, Syk and Src.
Rociletinib (CO-1686)

Rociletinib (CO-1686, AVL-301) is an irreversible, mutant-selective EGFR inhibitor with K_i of 21.5 nM and 303.3 nM for EGFR^L858R/T790M and EGFR^WT in cell-free assays, respectively. Phase 2.
AG-1478 (Tyrphostin AG-1478)

AG-1478 (Tyrphostin AG-1478, NSC 693255) is a selective EGFR inhibitor with IC50 of 3 nM in cell-free assays, almost no activity on HER2-Neu, PDGFR, Trk, Bcr-Abl and InsR. AG-1478 (Tyrphostin AG-1478) inhibits encephalomyocarditis virus (EMCV) and hepatitis c virus (HCV) by targeting phosphatidylinositol 4-kinase IIIα (PI4KA).

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Afatinib (BIBW2992)