Alisertib (MLN8237)

Name: Alisertib (MLN8237)
Brand: Selleck Chemicals
SKU: S1133
Rating: 5 (254 reviews)

For research use only.

Catalog No.S1133

254 publications

CAS No. 1028486-01-2

Alisertib (MLN8237) is a selective Aurora A inhibitor with IC50 of 1.2 nM in a cell-free assay. It has >200-fold higher selectivity for Aurora A than Aurora B. Alisertib induces cell cycle arrest, apoptosis and autophagy. Phase 3.

Selleck's Alisertib (MLN8237) has been cited by 254 publications

Cell, 2020, 182(3):685-712.e19

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Nature, 2019, 574(7777):268-272

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Science, 2019, 364(6447)

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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, 35(5):752-766

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Nat Med, 2016, 22(7):744-53

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Cancer Cell, 2014, 26(3):414-427

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Cell Stem Cell, 2012, 11(2):179-94

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EMBO Rep, 2021, e51902

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Cell Rep, 2021, 34(11):108870

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Haematologica, 2021, 10.3324/haematol.2021.278743

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PLoS Genet, 2021, 17(4):e1009327

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Neoplasia, 2021, 23(6):624-633

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Am J Cancer Res, 2021, 11(6):3240-3251

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Sci Rep, 2021, 11(1):10461

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Mol Pharmacol, 2021, 99(6):435-447

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Cancer Commun (Lond), 2021, 10.1002/cac2.12125

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Mol Cell Endocrinol, 2021, 528:111243

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Invest New Drugs, 2021, 10.1007/s10637-020-01019-9

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Sci Rep, 2021, 11(1):2616

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EMBO Rep, 2021, e51030

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Mol Cell, 2020, 80(6):1104-1122.e9

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J Clin Invest, 2020, 139080

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Nat Commun, 2020, 29;11(1):2086

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Oncogene, 2020, 16

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Cancer Lett, 2020, 495:135-144

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Cancers (Basel), 2020, 12(9)E2498

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Cancers (Basel), 2020, 12(3)

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Br J Cancer, 2020, 22

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Mol Cancer Ther, 2020, 10.1158/1535-7163.MCT-19-1017

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Am J Cancer Res, 2020, 10(10):3406-3414

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Mol Cancer Res, 2020, 8

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Mol Cancer Res, 2020, molcanres.1226.2019

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Front Oncol, 2020, 10:1354

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J Cell Sci, 2020, 133(24)jcs240267

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Dis Model Mech, 2020, dmm.44289

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J Cell Mol Med, 2020, 10.1111/jcmm.15901

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Int J Mol Sci, 2020, 21(18)E6690

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Sci Adv, 2020, 6(29):eaba1941

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Cancer Res, 2020, 80(16):3424-3435

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J Cancer, 2020, 11(8):2241-2251

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Front Cell Dev Biol, 2020, 8:857

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Cancer Lett, 2020, 491:50-59

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CU Digital Repository, 2020, N/A

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Nucleic Acids Res, 2020, gkaa570

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Nat Commun, 2019, 10(1):2189

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Nat Commun, 2019, 10(1):3485

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Nat Commun, 2019, 10(1):993

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Nat Commun, 2019, 10(1):2208

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Clin Cancer Res, 2019, 25(14):4552-4566

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Dev Cell, 2019, 50(3):355-366e6

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Cell Syst, 2019, 9(1):74-92.e8

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Cell Syst, 2019, 8(2):163-167

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Cell Rep, 2019, 26(2):293-301e7

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Oncogene, 2019, 38(1):73-87

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EBioMedicine, 2019, 41:120-133

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Cell Death Dis, 2019, 10(12):881

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Cancers (Basel), 2019, 11(2)

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Cell Death Dis, 2019, 10(8):606

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FASEB J, 2019, 33(4):4866-4882

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Cell Chem Biol, 2019, 10.1016/j.chembiol.2019.06.003

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Curr Biol, 2019, 29(21):3563-3578

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PLoS Negl Trop Dis, 2019, 13(5):e0007425

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Antiviral Res, 2019, 170:104572

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Mol Biol Cell, 2019, 30(3):312-323

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Toxicol Sci, 2019, 10.1093/toxsci/kfz123

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Sci Rep, 2019, 9(1):1897

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Sci Rep, 2019, 9(1):2211

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Int J Oncol, 2019, 55(4):938-948

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Transl Oncol, 2019, 12(4):683-692

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J Pediatr Hematol Oncol, 2019, 41(6):e359-e370

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Target Oncol, 2019, 14(5):563-575

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Oncotarget, 2019, 10(17):1649-1659

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Oncogene, 2019, 38(40):6696-6710

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Blood Adv, 2019, 3(21):3214-3227

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J Vis Exp, 2019, (151)

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Nat Chem Biol, 2018, 14(8):768-777

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Neuro Oncol, 2018, 20(2):203-214

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Curr Biol, 2018, 28(21):3458-3468e5

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Clin Cancer Res, 2018, 24(24):6594-6610

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J Cell Biol, 2018, 217(1):107-116

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Elife, 2018, doi: 107554/eLife38111

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Thyroid, 2018, doi: 101089/thy20180183

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Oncogene, 2018, 37(33):4599-4610

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Oncogene, 2018, 37(22):2921-2935

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Oncogene, 2018, 37(4):502-511

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BMC Biol, 2018, 16(1):116

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Cell Death Dis, 2018, 9(8):781

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Mol Cancer Ther, 2018, 17(12):2575-2585

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Mol Cancer Ther, 2018, 17(12):2551-2563

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Mol Cell Proteomics, 2018, 17(12):2434-2447

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Pharmacol Res, 2018, 134:166-178

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Mol Pharm, 2018, 15(8):3046-3059

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Int J Mol Sci, 2018, 19(12)

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Apoptosis, 2018, 23(9-10):492-511

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Cell Cycle, 2018, 17(5):652-668

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BMC Cancer, 2018, 18(1):922

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J Cancer, 2018, 9(12):2061-2071

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Cancer Med, 2018, 7(11):5589-5603

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Int J Mol Med, 2018, 41(6):3629-3641

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Pediatr Blood Cancer, 2018, 65(8):e27094

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Mol Med Rep, 2018, 18(1):1206-1210

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Anticancer Res, 2018, 38(6):3471-3476

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Oncotarget, 2018, 9(89):35875-35890

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Oncotarget, 2018, 9(65):32496-32506

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Sci Rep, 2018, 8(1):14017

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Oncotarget, 2018, 9(16):12769-12780

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SLAS Discov, 2018, 23(8):850-861

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J Neurooncol, 2018, 137(3):481-492

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R Soc Open Sci, 2018, 5(12):181303

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Sci Transl Med, 2017, 9(372)

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Mol Cell, 2017, 68(1):210-223e6

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Nat Commun, 2017, 8:14294

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Clin Cancer Res, 2017, 10.1158/1078-0432

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J Cell Biol, 2017, 216(11):3571-3590

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Oncogene, 2017,

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EBioMedicine, 2017, 24:43-55

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Plant Physiol, 2017, 173(1):582-599

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FASEB J, 2017, 32(2):625-638

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Cell Physiol Biochem, 2017, 43(1):94-107

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Mol Cancer Ther, 2017, 16(9):1934-1941

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Mol Cancer Ther, 2017,

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Mol Cancer Ther, 2017, 16(11):2552-2562

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Eur J Med Chem, 2017, 140:1-19

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Cell Discov, 2017, 3:16049

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Mol Cancer Res, 2017, 15(6):670-682

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J Cell Sci, 2017, 130(4):683-688

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Sci Rep, 2017, 7:45514

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J Biol Chem, 2017, 292(5):1910-1924

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BMC Cell Biol, 2017, 18(1):33

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Curr Cancer Drug Targets, 2017, 17(4):386-401

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Oncotarget, 2017, 8(10):16669-16689

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Oncotarget, 2017, 8(31):50376-50392

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Oncotarget, 2017, 8(19):32117-32133

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Sci Rep, 2017, 7(1):17978

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Oncotarget, 2017, 8(68):112313-112329

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Oncotarget, 2017, 8(12):19738-19759

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Oncotarget, 2017, 8(59):100326-100338

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Oncotarget, 2017, 8(70):114474-114480

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Oncotarget, 2017, 8(12):19478-19490

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Oncotarget, 2017, 8(54):92926-92942

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Pharmaceuticals (Basel), 2017, 10(3)

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Oncotarget, 2017, 8(31):50376-50392

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Oncotarget, 2017, 8(63):107076-107088

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Oncotarget, 2017, 8(34):57047-57057

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Nat Commun, 2016, 7:10180

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Nat Commun, 2016, 7:11389

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Nat Commun, 2016, 7:12674

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Elife, 2016, 5:e11402

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J Med Chem, 2016, 59(15):7188-211

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Cell Death Dis, 2016, 7:e2135

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Arch Toxicol, 2016, 291(10):4939-54

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Hum Mol Genet, 2016, 25(8):1574-87

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ACS Chem Biol, 2016, 11(12):3400-3411

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Sci Rep, 2016, 6:19567

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J Cell Biochem, 2016, 117(6):1340-51

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Cancer Biol Ther, 2016, 17(5):566-76

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Cell Cycle, 2016, 15(3):413-24

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Onco Targets Ther, 2016, 9:3473-84

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Biochem Biophys Res Commun, 2016, 475(3):251-6

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Exp Hematol, 2016, 44(4):247-56

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Mol Med Rep, 2016, 14(1):394-8

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Biol Bull, 2016, 231(1):61-72

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Oncotarget, 2016, 7(22):33152-64

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Oncotarget, 2016, 7(51):84718-84735

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Oncotarget, 2016, 7(51):84675-84687

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Nat Cell Biol, 2015, 17(2):113-22

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Nat Cell Biol, 2015, 17(2):113-22

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Nat Commun, 2015, 6:8388

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J Cell Biol, 2015, 210(1):45-62

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Mol Cancer, 2015, 14(1):83

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J Invest Dermatol, 2015, 135(9):2292-2300

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J Cell Sci, 2015, 128(2):364-72

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J Cell Sci, 2015, 128(3):527-40

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J Cell Sci, 2015, 128(3):516-26

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J Cell Sci, 2015, 128(20):3769-80

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J Cell Sci, 2015, 128(2):364-72

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Int J Mol Sci, 2015,

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Breast Cancer Res Tr, 2015, 149(3):715-26

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Cell Cycle, 2015, 14(24):3908-19

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Cell Cycle, 2015, 14(9):1447-58

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Drug Des Devel Ther, 2015, 9:1555-84

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Drug Des Devel Ther, 2015, 9:575-601

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BMC Res Notes, 2015, 8:484

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Genes Cancer, 2015, 6(5-6):184-213

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Oncotarget, 2015, 6(34):35247-62

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Clin Cancer Res, 2014, 34(5):2269-74

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Oncogene, 2014, 33(42):4985-96

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Oncogene, 2014, 33(27):3550-60

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Cell Death Dis, 2014, 5:e1253

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Cell Death Dis, 2014, 5:e1177

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Cell Death Dis, 2014, 6:e1595

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Endocr Relat Cancer, 2014, 21(5):797-811

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Mol Oncol, 2014, 8(8):1419-28

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Epigenetics, 2014, 9(4):611-20

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Mol Cancer Res, 2014, 12(3):433-9

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Biochim Biophys Acta, 2014, 1843(11):2719-2729

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J Transl Med, 2014, 12(1):200

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Mol Carcinog, 2014, 10.1002/mc.22223

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Cell Cycle, 2014, 13(14):2248-61

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FEBS Lett, 2014, 588(14):2198-205

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Chembiochem, 2014, 15(3):443-50

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PLoS One, 2014, 9(12):e113989

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PLoS One, 2014,

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Biochem Biophys Res Commun, 2014, 452(3):845-51

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Neurosci Lett, 2014, 583:199-204

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J Pediatr Surg, 2014, 49(1):159-65

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Oncotarget, 2014, 5(10):2947-61

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Oncotarget, 2014, 5(12):4071-86

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Oncotarget, 2014, 5(15):6229-42

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Nat Commun, 2013, 4:2656

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EMBO Mol Med, 2013, 5(1):149-66

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Leukemia, 2013, 27(3):560-8

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Proc Natl Acad Sci U S A, 2013, 110(19):E1779-87

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Cancer Res, 2013, 73(20):6310-22

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J Cell Biol, 2013, 202(3):463-78

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EMBO Rep, 2013, 14(9):829-36

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Int J Cancer, 2013, 135(3):751-62

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Oral Oncol, 2013, 49(6):551-9

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ACS Chem Biol, 2013, 8(7):1451-9

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J Cell Sci, 2013, 126(Pt 6):1355-65

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J Cell Sci, 2013, 126(Pt 9):2102-13

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Biochim Biophys Acta, 2013, 1833(10):2220-32

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Epigenetics Chromatin, 2013, 6(1):21

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J Biol Chem, 2013, 289(1):74-88

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Cancer Biol Ther, 2013, 14(5):436-49

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PLoS One, 2013, 8(5):e64306

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PLoS One, 2013, 8(9):e73548

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Oncotarget, 2013,

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J Biol Chem, 2012, 287(33):27670-81

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Breast Cancer Res Tr, 2012, 135(2):433-44

PubMed: 22825030 ( click the link to review the publication )

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PubMed: 22214762 ( click the link to review the publication )

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PubMed: 22359551 ( click the link to review the publication )

EMBO J, 2011, 30(5):906-19

PubMed: 21297582 ( click the link to review the publication )

Mol Cancer, 2011, 10:131

PubMed: 22011530 ( click the link to review the publication )

Oncotarget, 2011,

PubMed: 21865609 ( click the link to review the publication )

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PubMed: 21187329 ( click the link to review the publication )

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Purity & Quality Control

Choose Selective Aurora Kinase Inhibitors

Biological Activity

Description

Features

First orally available inhibitor of Aurora A.

Targets

Aurora A ^[1]
(Cell-free assay)

1.2 nM

In vitro

MLN8237 shows >200-fold higher selectivity for Aurora A than the structurally related Aurora B with an IC50 of 396.5 nM, and does not have any significant activity against 205 other kinases. ^[1] MLN8237 (0.5 μM) treatment inhibits the phosphorylation of Aurora A in MM1.S and OPM1 cells, without affecting the Aurora B mediated histone H3 phosphorylation. MLN8237 significantly inhibits cell proliferation in multiple myeloma (MM) cell lines with IC50 values of 0.003-1.71 μM. MLN8237 displays more potent anti-proliferation activity against primary MM cells and MM cell lines in the presence of BM stroma cells, as well as IL-6 and IGF-1 than against MM cells alone. MLN8237 (0.5 μM) induces 2- to 6-fold increase in G2/M phase in primary MM cells and cell lines, as well as significant apoptosis and senescence, involving the up-regulation of p53, p21 and p27, as well as PARP, caspase 3, and caspase 9 cleavage. In addition, MLN8237 shows strong synergistic anti-MM effect with dexamethasone, as well as additive effect with doxorubicin and bortezomib. ^[2] MLN8237 (0.5 μM) treatment causes the inhibition of colony formation of FLO-1, OE19, and OE33 esophageal adenocarinoma cell lines, and induces a significant increase in the percentage of polyploid cells, and subsequently an increase in the percentage of cells in the sub-G1 phase, which can be further enhanced in combination with cisplatin (2.5 μM), involving the higher induction of TAp73β, PUMA, NOXA, cleaved caspase-3, and cleaved PARP as compared with a single-agent treatment. ^[3]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
HCT116	MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NGXPbXcxNjVizszN	M3jueFczKGh?	MVLEUXNQ	NV7sNpgzUUN3ME2wMlA1KM7:TR?=	MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF\|Nk[4OEc,OjZzM{[2PFQ9N2F-
LS174T	MmftS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M{\nTlAvPSEQvF2=	MkXPO\|IhcA>?	MVrEUXNQ	Ml7GTWM2OD1yLkC1JO69VQ>?	NEPxUlQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGzOlY5PCd-Mk[xN\|Y3QDR:L3G+
T84	MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NUjhWWxDOC53IN88US=>	MW[3NkBp	MmPVSG1UVw>?	NH33[IFKSzVyPUCuNFkh\|ryP	MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF\|Nk[4OEc,OjZzM{[2PFQ9N2F-
LS180	NFPwSnlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NXu1OVB1OC53IN88US=>	MXG3NkBp	MoTnSG1UVw>?	M4PwNmlEPTB;MTFOwG0>	Ml:wQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzM{[2PFQoRjJ4MUO2Olg1RC:jPh?=
SW948	MULHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M{mye\|AvPSEQvF2=	NHPLd4U4OiCq	NEHiZWlFVVOR	M1vMNmlEPTB;MTFOwG0>	Mm\PQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZzM{[2PFQoRjJ4MUO2Olg1RC:jPh?=
HCT15	MVzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MoXjNE42KM7:TR?=	NH7vZmI4OiCq	NIO1dW9FVVOR	MmexTWM2ODxyLkSg{txO	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjF\|Nk[4OEc,OjZzM{[2PFQ9N2F-
DLD-1	M2TrV2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NYPSfmNvOC53IN88US=>	MXG3NkBp	NVqwWY1kTE2VTx?=	NYPOZph{UUN3MEywMlgh\|ryP	M363T\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUO2Olg1Lz5{NkGzOlY5PDxxYU6=
MIP-101	MlTXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NGqxUFkxNjVizszN	NFHVTIw4OiCq	NF7JcZZFVVOR	NH3WOmtKSzVyPUGg{txO	NH;zVlA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGzOlY5PCd-Mk[xN\|Y3QDR:L3G+
SNU1544	M3ywXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M1jKb\|AvPSEQvF2=	M4TYNFczKGh?	NX;TRok6TE2VTx?=	MnXMTWM2OD1zIN88US=>	NUnzem8{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xN\|Y3QDRpPkK2NVM3Pjh2PD;hQi=>
OCI-Ly10	NFK5SoVEgXSxdH;4bYMhSXO\|YYm=		MWS3NkBp	M4G3TGROW09?	MX;JR\|UxRTBwMEW4JO69VQ>?	MoPRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6N{izN\|EoRjJ3OEe4N\|MyRC:jPh?=
SU-DHL2	NGrnXmhEgXSxdH;4bYMhSXO\|YYm=		NHLF[\|I4OiCq	NET3VFJFVVOR	NULIfYM3UUN3ME2wMlAyKM7:TR?=	M3nhblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEe4N\|MyLz5{NUi3PFM{OTxxYU6=
OCI-LY7	M1LlcWN6fG:2b4jpZ{BCe3OjeR?=		Ml;FO\|IhcA>?	M3LVVmROW09?	NFK4c4NKSzVyPUCuNFgyKM7:TR?=	MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh5OEOzNUc,OjV6N{izN\|E9N2F-
SU-DHL6	Ml;VR5l1d3SxeHnjJGF{e2G7		MlK1O\|IhcA>?	NY\BOIJrTE2VTx?=	MojUTWM2OD1yLkS4NkDPxE1?	NYTHT5VkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4O\|g{OzFpPkK1PFc5OzNzPD;hQi=>
Jeko-1	MnzWR5l1d3SxeHnjJGF{e2G7		MVG3NkBp	MWPEUXNQ	NW\3d4ZrUUN3ME2wMlAzQSEQvF2=	MnHVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6N{izN\|EoRjJ3OEe4N\|MyRC:jPh?=
JVM-2	NHnCR4REgXSxdH;4bYMhSXO\|YYm=		MmH1O\|IhcA>?	M2PtOGROW09?	MnzaTWM2OD1yLkCxJO69VQ>?	NYjwTm9sRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4O\|g{OzFpPkK1PFc5OzNzPD;hQi=>
Rec-1	NXHZXnBxS3m2b4TvfIlkKEG\|c3H5		M{LsV\|czKGh?	M1TMWGROW09?	M{D6ZmlEPTB;MD6wPFch\|ryP	NVjxSYdFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4O\|g{OzFpPkK1PFc5OzNzPD;hQi=>
Z-138	MXTDfZRwfG:6aXOgRZN{[Xl?		MXW3NkBp	M4jHTmROW09?	NHnOd21KSzVyPUCuNFE{KM7:TR?=	NV3NSYxzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4O\|g{OzFpPkK1PFc5OzNzPD;hQi=>
H9	MXLDfZRwfG:6aXOgRZN{[Xl?		MnHvO\|IhcA>?	MkTCSG1UVw>?	NFPVb3hKSzVyPUCuOkDPxE1?	Mo\LQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6N{izN\|EoRjJ3OEe4N\|MyRC:jPh?=
HH	MnfCR5l1d3SxeHnjJGF{e2G7		NEPj[oo4OiCq	MnrlSG1UVw>?	NGTofW9KSzVyPUCuO{DPxE1?	NGGyOZE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUi3PFM{OSd-MkW4O\|g{OzF:L3G+
DND41	Ml\yR5l1d3SxeHnjJGF{e2G7		MnPvO\|IhcA>?	M2qzZmROW09?	NIjqcZpKSzVyPUCuNUDPxE1?	NH\ET\|k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUi3PFM{OSd-MkW4O\|g{OzF:L3G+
CCL119	M2rQbWN6fG:2b4jpZ{BCe3OjeR?=		MUO3NkBp	MlnHSG1UVw>?	MWPJR\|UxRTBwME[yJO69VQ>?	MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh5OEOzNUc,OjV6N{izN\|E9N2F-
J.Cam 1.6	NGribJpEgXSxdH;4bYMhSXO\|YYm=		NUX6c417PzJiaB?=	MX7EUXNQ	M13u[WlEPTB;MD6xNFUh\|ryP	MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh5OEOzNUc,OjV6N{izN\|E9N2F-
Sup-T1	MWjDfZRwfG:6aXOgRZN{[Xl?		MlzXO\|IhcA>?	M1zhd2ROW09?	MWjJR\|UxRTJwMUSyJO69VQ>?	MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh5OEOzNUc,OjV6N{izN\|E9N2F-
Tib 152	M4PrOmN6fG:2b4jpZ{BCe3OjeR?=		MXy3NkBp	NH;zdpBFVVOR	NVfrcnR5UUN3ME2wMlgh\|ryP	NUXFSGlMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4O\|g{OzFpPkK1PFc5OzNzPD;hQi=>
MCF7	M4\PfWZ2dmO2aX;uJGF{e2G7	MVS1JO69VQ>?	MknnNlQhcA>?	NW[5SXVTTE2VTx?=	NWC4PGRxUW6mdXPld{BIOi:PIHHydoV{fA>?	NEjzSng9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
MDA-MB-231	M3jvRmZ2dmO2aX;uJGF{e2G7	MVm1JO69VQ>?	Mn;pNlQhcA>?	M3PzNWROW09?	MoHHTY5lfWOnczDHN{9OKGG{cnXzeC=>	M3L6XVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
MCF7	NIq0e2lHfW6ldHnvckBCe3OjeR?=	NVe3Tpo3PSEQvF2=	MVOyOEBp	NYHWOVgzTE2VTx?=	NULyUGRETGWlcnXhd4V{KHSqZTDlfJBz\XO\|aX;uJIxmfmWuIH;mJGNFUzFxQ1TDNi=>	NX3sPG96RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|Q1ODFpPkK1PFM1PDBzPD;hQi=>
MCF7	M4fkNmZ2dmO2aX;uJGF{e2G7	NHXDNYY2KM7:TR?=	MWqyOEBp	NYHGOFY3TE2VTx?=	NHjudGtF\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gR2RMOg>?	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh\|NESwNUc,OjV6M{S0NFE9N2F-
MCF7	NFSzc2xHfW6ldHnvckBCe3OjeR?=	MWq1JO69VQ>?	MWiyOEBp	MXPEUXNQ	MXzE[YNz\WG\|ZYOgeIhmKGW6cILld5Nqd25ibHX2[Ywhd2ZiY4njcIlvKEJz	NF\CSYU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
MCF7	NILV[ZBHfW6ldHnvckBCe3OjeR?=	NI\FUJg2KM7:TR?=	M2naPVI1KGh?	MUHEUXNQ	MlPXTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyNUBY[WZzL1PpdFE>	NIG2TnE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
MCF7	NIHFTGVHfW6ldHnvckBCe3OjeR?=	M2nuO\|Uh\|ryP	MoXMNlQhcA>?	NGHqVHRFVVOR	NFHiNlVKdmO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gdFI4KEurcEG=	NITl[YU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOFQxOSd-MkW4N\|Q1ODF:L3G+
MDA-MB-231	NHjSeoRHfW6ldHnvckBCe3OjeR?=	MYq1JO69VQ>?	NYfTXoNuOjRiaB?=	MXPEUXNQ	NHHYVXpF\WO{ZXHz[ZMhfGinIHX4dJJme3Orb36gcIV3\Wxib3[gR2RMOS:FRFOy	MkewQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6M{S0NFEoRjJ3OEO0OFAyRC:jPh?=
MDA-MB-231	M1z6fGZ2dmO2aX;uJGF{e2G7	MVKxJO69VQ>?	Ml7sNlQhcA>?	NV;lSoR5TE2VTx?=	M1G5Wmlv[3KnYYPld{B1cGViZYjwdoV{e2mxbjDs[ZZmdCCxZjDDSGsz	NV3EOpVCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|Q1ODFpPkK1PFM1PDBzPD;hQi=>
MDA-MB-231	NEn5S4hHfW6ldHnvckBCe3OjeR?=	MlHuOUDPxE1?	NWLvN2d4OjRiaB?=	NVzEflBOTE2VTx?=	NVu3VVZ4TGWlcnXhd4V{KHSqZTDlfJBz\XO\|aX;uJIxmfmWuIH;mJIN6[2yrbjDCNS=>	M2LURlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
MDA-MB-231	M371WmZ2dmO2aX;uJGF{e2G7	MUe1JO69VQ>?	NVvzXldCOjRiaB?=	MWLEUXNQ	Mn\oTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyNUBY[WZzL1PpdFE>	MnL4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6M{S0NFEoRjJ3OEO0OFAyRC:jPh?=
MDA-MB-231	M1jJOGZ2dmO2aX;uJGF{e2G7	MUK1JO69VQ>?	NEi5V4MzPCCq	MWLEUXNQ	MlLRTY5kemWjc3XzJJRp\SCneIDy[ZN{cW:wIHzleoVtKG:oIICyO{BMcXBz	NVXBW\|Y{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|Q1ODFpPkK1PFM1PDBzPD;hQi=>
MDA-MB-231	MXnGeY5kfGmxbjDBd5NigQ>?	NI\BNmc2KM7:TR?=	NFzEelkzPCCq	NXzSPZh[TE2VTx?=	NUTaRWt5UW6lcnXhd4V{KHSqZTDlfJBz\XO\|aX;uJIxmfmWuIH;mJJA2Ow>?	MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh\|NESwNUc,OjV6M{S0NFE9N2F-
MCF7	MmS5RZBweHSxc3nzJGF{e2G7	M{jVdlUh\|ryP	NU\ieYZIOjRiaB?=	M{H3TmROW09?	NWD1VnVvUW6mdXPld{BieG:ydH;0bYMh\GWjdHi=	M1HYN\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
MDA-MB-231	NXXXTnlpSXCxcITvd4l{KEG\|c3H5	NILoVnA2KM7:TR?=	MW[yOEBp	NX7ydoh{TE2VTx?=	M3TLR2lv\HWlZYOgZZBweHSxdHnjJIRm[XSq	MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh\|NESwNUc,OjV6M{S0NFE9N2F-
MCF7	MkXWSpVv[3Srb36gRZN{[Xl?	MWixJO69VQ>?	NYT4PJZ[PzJiaB?=	MonxSG1UVw>?	MoG1TY5lfWOnczDheZRweGijZ3njJIRm[XSq	MniyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6M{S0NFEoRjJ3OEO0OFAyRC:jPh?=
MDA-MB-231	NEHETYxHfW6ldHnvckBCe3OjeR?=	NV;QZnNDOSEQvF2=	MXq3NkBp	NWfidHpMTE2VTx?=	MXfJcoR2[2W\|IHH1eI9xcGGpaXOg[IVifGh?	M{TCXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEO0OFAyLz5{NUizOFQxOTxxYU6=
U-2 OS	NXrabHBQT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	M1jhUFUxKM7:TR?=	NF[1PZAzPCCq	NVvrU4V5TE2VTx?=	M2[1cGlEPTB;MU[uOkDPxE1?	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd7MkixNUc,OjV5OUK4NVE9N2F-
MG-63	M1[0emdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NYXmbHAxPTBizszN	M2Lqd\|I1KGh?	Mn3iSG1UVw>?	NIHn[FVKSzVyPUmuOUDPxE1?	NV;SXHdXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3PVI5OTFpPkK1O\|kzQDFzPD;hQi=>
U-2 OS	NV7nb5RuSXCxcITvd4l{KEG\|c3H5	M2H3N\|Uh\|ryP	Ml;sNlQhcA>?	NXj5W25DTE2VTx?=	NFvGSJNKdmS3Y3XzJIFxd3C2b4TpZ{Bk\WyuIHTlZZRp	NGXSSok9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe5NlgyOSd-MkW3PVI5OTF:L3G+
MG-63	M4jBWmFxd3C2b4Ppd{BCe3OjeR?=	M3vwT\|Uh\|ryP	MlzhNlQhcA>?	MWTEUXNQ	MXfJcoR2[2W\|IHHwc5B1d3SrYzDj[YxtKGSnYYTo	NGDWXYU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe5NlgyOSd-MkW3PVI5OTF:L3G+
U-2 OS	NVvvW2xrTnWwY4Tpc44hSXO\|YYm=	MoC5OUDPxE1?	MYWyOEBp	MWfEUXNQ	MmP2VJJwdW:2ZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp	NEjpSHI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe5NlgyOSd-MkW3PVI5OTF:L3G+
MG-63	M3\hdWZ2dmO2aX;uJGF{e2G7	NVnNc41iPSEQvF2=	M{DUT\|I1KGh?	NFf2U5dFVVOR	NHLP[XZRem:vb4Tld{BifXSxcHjh[4lkKGOnbHyg[IVifGh?	M{TCcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{myPFEyLz5{NUe5NlgyOTxxYU6=
PANC-1	NF2xTpFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	Mn\wOVAh\|ryP	NWHq[WpsOjRiaB?=	MojhSG1UVw>?	NGrPV2lKSzVyPUeuNUDPxE1?	MoDUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV4M{KyNlUoRjJ3NkOyNlI2RC:jPh?=
BxPC-3	MWrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M4HWclUxKM7:TR?=	NUXuV5dzOjRiaB?=	MY\EUXNQ	NXPhfpZRUUN3ME22Mlgh\|ryP	MonqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV4M{KyNlUoRjJ3NkOyNlI2RC:jPh?=
PANC-1	MXzGeY5kfGmxbjDBd5NigQ>?	Mm\qOUDPxE1?	NUC1RYQ5OjRiaB?=	MYrEUXNQ	NH3hb\|lKdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0JIlvKEd{L12gdIhie2V?	M4O1RVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkOyNlI2Lz5{NU[zNlIzPTxxYU6=
BxPC-3	M2nVN2Z2dmO2aX;uJGF{e2G7	M{\CdlUh\|ryP	M4LPOVI1KGh?	MlLKSG1UVw>?	M4\jWmlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4SgbY4hTzJxTTDwbIF{\Q>?	MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ\|MkKyOUc,OjV4M{KyNlU9N2F-
PANC-1	NILRUI9HfW6ldHnvckBCe3OjeR?=	M2TJW\|Uh\|ryP	NHvYSYszPCCq	M3q3dGROW09?	MmrvTY5lfWOnczDheZRweGijZ3njJINmdGxiZHXheIg>	MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ\|MkKyOUc,OjV4M{KyNlU9N2F-
BxPC-3	Mn3kSpVv[3Srb36gRZN{[Xl?	M1zsUlUh\|ryP	NInHUJUzPCCq	M2q4bWROW09?	M3H1eWlv\HWlZYOgZZV1d3CqYXfpZ{Bk\WyuIHTlZZRp	MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ\|MkKyOUc,OjV4M{KyNlU9N2F-
SKOV3	MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NILjZlQyODBizszN	NX2xfpZzOjRiaB?=	MnHMSG1UVw>?	MXTJR\|UxRTJyLkS4JO69VQ>?	MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ{NEe1NEc,OjV4MkS3OVA9N2F-
OVCAR4	MX;Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M4L5NFExOCEQvF2=	Mnr2NlQhcA>?	NYntVotZTE2VTx?=	M{jmb2lEPTB;MkKuNVMh\|ryP	NV7yRoVCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2NlQ4PTBpPkK1OlI1PzVyPD;hQi=>
SKOV3	NYPDXYZyTnWwY4Tpc44hSXO\|YYm=	Mk[wOUDPxE1?	NF71WmU4OiCq	M4rlVWROW09?	NYLTT25FUW6mdXPld{BIOi:PIHHydoV{fA>?	NXfjOFRSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2NlQ4PTBpPkK1OlI1PzVyPD;hQi=>
OVCAR4	MWLGeY5kfGmxbjDBd5NigQ>?	M4fTdVUh\|ryP	MXS3NkBp	M3HYfWROW09?	M1fWPWlv\HWlZYOgS\|IwVSCjcoLld5Q>	MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ{NEe1NEc,OjV4MkS3OVA9N2F-
SKOV3	MXXBdI9xfG:\|aYOgRZN{[Xl?	NYDJO4M{PSEQvF2=	NHXRS48zPCCq	NUfreXRCTE2VTx?=	MU\JcoR2[2W\|IHHwc5B1d3Orcx?=	NIWyNHg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[yOFc2OCd-MkW2NlQ4PTB:L3G+
OVCAR4	M{\hSmFxd3C2b4Ppd{BCe3OjeR?=	M2TmfFUh\|ryP	M2nJXFI1KGh?	NWDneHZuTE2VTx?=	MVPJcoR2[2W\|IHHwc5B1d3Orcx?=	NGTV[YU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[yOFc2OCd-MkW2NlQ4PTB:L3G+
AGS	NIDNVW5Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MYKyOUDPxE1?	NXe4NJR[OjRiaB?=	MmHRSG1UVw>?	NUXIUYlHUUN3ME2xPU4xQSEQvF2=	NV;PWXQ2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2NFk6OjNpPkK1OlA6QTJ\|PD;hQi=>
NCI-N78	NXLzdIVqT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MWWyOUDPxE1?	NIiwUJczPCCq	NUHVZmFDTE2VTx?=	NFj0NoJKSzVyPUK2MlM{KM7:TR?=	M{PBUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkC5PVI{Lz5{NU[wPVkzOzxxYU6=
AGS	MlrSRZBweHSxc3nzJGF{e2G7	MX[1JO69VQ>?	MojaNlQhcA>?	MUfEUXNQ	M1X0emlv\HWlZYOgZZBweHSxc3nz	M2Dx[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkC5PVI{Lz5{NU[wPVkzOzxxYU6=
NCI-N78	NFT1UmFCeG:ydH;zbZMhSXO\|YYm=	MljHOUDPxE1?	NWDMXVVsOjRiaB?=	NFztVmxFVVOR	M1TDemlv\HWlZYOgZZBweHSxc3nz	NXTlUVBvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2NFk6OjNpPkK1OlA6QTJ\|PD;hQi=>
AGS	NVv0OYJFTnWwY4Tpc44hSXO\|YYm=	NV7CeGl2PSEQvF2=	MViyOEBp	NYmwfXFMTE2VTx?=	M{HUXmlv\HWlZYOgeIhmKGG3dH;wbIFogQ>?	NXLLdlR7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2NFk6OjNpPkK1OlA6QTJ\|PD;hQi=>
NCI-N78	M1PUZmZ2dmO2aX;uJGF{e2G7	MXu1JO69VQ>?	MVOyOEBp	NULITnR4TE2VTx?=	NEnTUZFKdmS3Y3XzJJRp\SCjdYTvdIhi\3l?	MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZyOUmyN{c,OjV4MEm5NlM9N2F-
HSC-3	M{XN[2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MUOxJO69VQ>?	NVzJcZN3PDhiaB?=		NFXZO\|VKSzVyPUCuOVQh\|ryP	NFK5TlA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUO2OlE1Oyd-MkWzOlYyPDN:L3G+
GB30	M3nwTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NXrnTFR5OSEQvF2=	MUS3JIQ>	NHfxVmRFVVOR	MXHJR\|UxRTBwMEGxJO69VQ>?	NY[5R4JrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWxNFY1OjhpPkK1NVA3PDJ6PD;hQi=>
GB9	NVjZ[W9OT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NFjy[mEyKM7:TR?=	MlP6O{Bl	NX;KNYlwTE2VTx?=	NHzzUFJKSzVyPUCuNFI1KM7:TR?=	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTFyNkSyPEc,OjVzME[0Nlg9N2F-
GB169	M4LDN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MXixJO69VQ>?	NX64Z21EPyCm	M2nEPWROW09?	M3H1W2lEPTB;MD6wN\|Ih\|ryP	MlHPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjVzME[0NlgoRjJ3MUC2OFI5RC:jPh?=
T24	Ml3PSpVv[3Srb36gRZN{[Xl?	NYXVUWFmOSEQvF2=	NVX5U21WPDhiaB?=	NFP3XoZFVVOR	M{eybWlv\HWlZYOgZ4VtdCCleXPs[UBienKnc4S=	NIfwVGU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{SwN\|Y{Oyd-MkO0NFM3OzN:L3G+
RT4	M4rDT2Z2dmO2aX;uJGF{e2G7	NGPMfGQyKM7:TR?=	MonzOFghcA>?	M4S2PGROW09?	NEi1WphKdmS3Y3XzJINmdGxiY4njcIUh[XK{ZYP0	M1XjbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NECzOlM{Lz5{M{SwN\|Y{OzxxYU6=
UM-UC-3	NV\MVIdXTnWwY4Tpc44hSXO\|YYm=	NVLnOWM{OSEQvF2=	NHrUdZg1QCCq	NIfRcIZFVVOR	MlXUTY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dB?=	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzRyM{[zN{c,OjN2MEO2N\|M9N2F-
T24	NUjyUYc5SXCxcITvd4l{KEG\|c3H5	NXO4PWNnOy5zNjFOwG0>	MofSPVYhcA>?	NVGyVW0xTE2VTx?=	MVXJR\|UxRTBwMEOwOkDPxE1?	MlvRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2MEO2N\|MoRjJ\|NECzOlM{RC:jPh?=
RT4	MlWwRZBweHSxc3nzJGF{e2G7	NFWxZ2k{NjF4IN88US=>	MoXBPVYhcA>?	NX3KUJoyTE2VTx?=	NGPpfGNKSzVyPUCuNVE6QCEQvF2=	Mo[wQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2MEO2N\|MoRjJ\|NECzOlM{RC:jPh?=
UM-UC-3	NXvW[3dPSXCxcITvd4l{KEG\|c3H5	NYLNe2RMOy5zNjFOwG0>	MXO5OkBp	NUniVJBzTE2VTx?=	M2[xTmlEPTB;MD6wOFQ6KM7:TR?=	MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzRyM{[zN{c,OjN2MEO2N\|M9N2F-
OVCAR-5	MkfISpVv[3Srb36gRZN{[Xl?	M4rmVlUxKG6P			NETlR5VKdmirYnn0d{Bk\WyuIH3p[5JifGmxbh?=	NHXlOoU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{OzOFMzPyd-MkOzN\|Q{Ojd:L3G+
SKOV3ip2	NYXFdXNpTnWwY4Tpc44hSXO\|YYm=	NVHqeFVnPTBibl2=			Moj4TY5pcWKrdIOgZ4VtdCCvaXfyZZRqd25?	MmizQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN\|M{SzNlcoRjJ\|M{O0N\|I4RC:jPh?=
S462	MYLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MmPINVAxKM7:TR?=	MXS3NkBp	M1XodmROW09?	NH7ONWRCfHSnboXheIV{KGOnbHyg[5Jwf3Sq	NVfwfpkxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOzNlgyOTRpPkKzN\|I5OTF2PD;hQi=>
2884	MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NIruWIkyODBizszN	MUi3NkBp	MoLQSG1UVw>?	M4f1TWF1fGWwdXH0[ZMh[2WubDDndo94fGh?	NHPr[ZI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{OyPFEyPCd-MkOzNlgyOTR:L3G+
2885	M3rHVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MY[xNFAh\|ryP	NVzvVIw5PzJiaB?=	MX3EUXNQ	NFLqNGtCfHSnboXheIV{KGOnbHyg[5Jwf3Sq	NEPy[I49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{OyPFEyPCd-MkOzNlgyOTR:L3G+
CRL-2396	NY\ISXFyT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	M1LrUlExOCEQvF2=		M4n5eJdifGW{	MmPETWM2OD1yLkC5NkDPxE1?	NXLMPHhsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOxOVM2OjRpPkKzNVU{PTJ2PD;hQi=>
TIB-48	MomyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MoO4NVAxKM7:TR?=		NX\4SHg1f2G2ZYK=	NVvwfXVlUUN3ME2wMlA5QCEQvF2=	MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzF3M{WyOEc,OjNzNUO1NlQ9N2F-
CRL-2396	Mlm0R5l1d3SxeHnjJGF{e2G7	NIHvNWwyKM7:TR?=	MkW4OFghcA>?	NHzGcGZ4[XSnch?=	M2fj[Wlv\HWlZYOgZZBweHSxc3nz	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzF3M{WyOEc,OjNzNUO1NlQ9N2F-
TIB-48	MnfFR5l1d3SxeHnjJGF{e2G7	MWKxJO69VQ>?	MmfjOFghcA>?	NXXwfVlqf2G2ZYK=	NGnSeHNKdmS3Y3XzJIFxd3C2b4Ppdy=>	MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzF3M{WyOEc,OjNzNUO1NlQ9N2F-
AGS	MUnDfZRwfG:6aXOgRZN{[Xl?	NHLub3kxNjVizszN	NHeyPJozPCCq	MoLHSG1UVw>?	M1e0N2Rm[3KnYYPld{Bk\WyuIIP1dpZqfmGu	M{HPOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OUeyOlEyLz5{Mkm3NlYyOTxxYU6=
FLO-1	MVPDfZRwfG:6aXOgRZN{[Xl?	MVuwMlUh\|ryP	M1\5bFI1KGh?	M1jINmROW09?	MVnE[YNz\WG\|ZYOgZ4VtdCC\|dYL2bZZidA>?	MnfYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ7N{K2NVEoRjJ{OUeyOlEyRC:jPh?=
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TC-32	NWrRV3R[T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NWXOWIpnOTBizszN	NHX2WVE6PiCq	NUfVXnhNTE2VTx?=	M{na[mlEPTB;MD6wN\|kh\|ryP	NULrUXdvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG0OFg2QTFpPkKxOFQ5PTlzPD;hQi=>
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CHLA-9	M4\vNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MlL5NVAh\|ryP	Ml[zPVYhcA>?	MoSwSG1UVw>?	MkK4TWM2OD1yLkCxPEDPxE1?	NVzaNWNwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG0OFg2QTFpPkKxOFQ5PTlzPD;hQi=>
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LA-N-6	M4n5UWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	Mm\GNVAh\|ryP	Mor2PVYhcA>?	NXTMc\|hPTE2VTx?=	NY\sWFY3UUN3ME2wMlA2PCEQvF2=	NIPGUoE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUS0PFU6OSd-MkG0OFg2QTF:L3G+
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NCI-H358	M17l[GFvfGmycn;sbYZmemG2aY\lJIF{e2G7		MV[3NkBpenN?		MX\BcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE6FST3IN\|U5KGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDXV3Q5KGG\|c3H5MEBKSzVyIE2gNE4yKM7:TT6=	NWDFXW9CRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2NlU3OTdpPkK1OlI2PjF5PD;hQi=>
MIAPaCa2	MlnmRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		MnTsO\|IhcHK\|		NXH2N\|gxSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDNTWFR[UOjMjDj[YxteyCjZoTldkA4OiCqcoOgZpkhX1OWODDhd5NigSxiSVO1NEA:KDBwMUOg{txONg>?	Mnu1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV4MkW2NVcoRjJ3NkK1OlE4RC:jPh?=
PC14	MmrsRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		M3H2SlczKGi{cx?=		NG\rUHpCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGDDNVQh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IGfTWFgh[XO\|YYmsJGlEPTBiPTCwMlE4KM7:TT6=	NGrLS4w9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[yOVYyPyd-MkW2NlU3OTd:L3G+
HT-29	NV\IW3g4SW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		Mo\5O\|IhcHK\|		MnPLRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCKVD2yPUBk\WyuczDh[pRmeiB5MjDodpMh[nliV2PUPEBie3OjeTygTWM2OCB;IECuN\|Mh\|ryPLh?=	NHTOS3c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[yOVYyPyd-MkW2NlU3OTd:L3G+
HCT15	MX\BcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		M3G3fVczKGi{cx?=		NYfKZlJqSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDIR3QyPSClZXzsd{Bi\nSncjC3NkBpenNiYomgW3NVQCCjc4PhfUwhUUN3MDC9JFAvPzRizszNMi=>	MmjVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV4MkW2NVcoRjJ3NkK1OlE4RC:jPh?=
Sf9	MYjGeY5kfGmxbjDhd5NigQ>?				NVH3ZVFVS2:vcHX0bZRqfmViaX7obYJqfGmxbjDv[kBz\WOxbXLpcoFvfCCvb4Xz[UBifXKxcnGgb4lv[XOnIFGg[ZhxemW\|c3XkJIlvKGmwc3XjeEBU\jliY3XscJMhcW5icILld4Vv[2Vib3[gRXRRNCCNaTC9JFAvODByMzFOwG0v	M1izO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MUCxOVY1Lz5{NkGwNVU3PDxxYU6=
Sf9	Mof0SpVv[3Srb36gZZN{[Xl?				M3jHWmlvcGmkaYTpc44hd2ZicnXjc41jcW6jboSgcY92e2ViYYXyc5JiKGurbnHz[UBCKGW6cILld5Nm\CCrbjDpcpNm[3RiU3[5JINmdGy\|IIXzbY5oKGKrb4Tpck1IVFKUQWPMS{BieyC\|dXLzeJJifGViaX6gdJJme2WwY3Wgc4YhY2ejbX3hMVM{WF2DVGCsJGlEPTBiPTCwMlAxOSEQvF2u	NYrpTYFtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[xNFE2PjRpPkK2NVAyPTZ2PD;hQi=>
HCT116	MVXGeY5kfGmxbjDhd5NigQ>?				NV:zZpVEUW6qaXLpeIlwdiCxZjDheZJwemFia3nuZZNmKEFiYYX0c5Bpd3OyaH;yfYxifGmxbjDheEBVOjh6IHnuJIh2dWGwIFjDWFEyPiClZXzsd{BjgSCrbX31co9ndHWxcnXzZ4Vv[2ViYX7hcJl{cXNuIFnDOVAhRSByLkCwO{DPxE1w	MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjFyMUW2OEc,OjZzMEG1OlQ9N2F-
HCT116	M3fJ[mN6fG:2b4jpZ4l1gSCjc4PhfS=>				MUPDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDIR3QyOTZiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBk\WyuIIDyc4xq\mW{YYTpc44h[nliQoLkWUBqdmOxcoDvdoF1cW:wIHHzd4F6NCCJSUWwJF0hOC5yMzFOwG0v	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjFyMUW2OEc,OjZzMEG1OlQ9N2F-
HCT116	M{D1WWZ2dmO2aX;uJIF{e2G7				NXzC[FJGUW6qaXLpeIlwdiCxZjDheZJwemFia3nuZZNmKEJiaX6gbJVu[W5iSFPUNVE3KGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gbIl{fG:wZTDIN{BxcG:\|cHjvdplt[XSrb36gZpkhcW2vdX7v[ox2d3Knc3PlcoNmKGGwYXz5d4l{NCCLQ{WwJF0hOS53IN88UU4>	NHrjNlI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkGwNVU3PCd-Mk[xNFE2PjR:L3G+
BL21 (DE3) Rosetta	MlTmSpVv[3Srb36gZZN{[Xl?		NFG1Z\|Q{OCCvaX7z		NFvVUYFKdmirYnn0bY9vKG:oIFjpd{11[WepZXSgbJVu[W5iQYXyc5JiKEFia3nuZZNmKChzMkKgeI8hPDBicnXzbYR2\XNrIHX4dJJme3OnZDDpckBGe2OqZYLpZ4hq[SClb3zpJGJNOjFiKFTFN{khWm:\|ZYT0ZUBk\WyuczD1d4lv\yCkaX;0bY56dGG2ZXSgV3RMOiC\|dXLzeJJifGViaX7jeYJifGWmIH\vdkA{OCCvaX7zJIJ6KEiWUl[gZZN{[XluIFnDOVAhRSByLkCwNFA1KM7:TT6=	M1G3VFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5M{mxNVM{Lz5{N{O5NVE{OzxxYU6=
HeLa Kyoto	NI\NPHVHfW6ldHnvckBie3OjeR?=		NGjESpEzOCCqcoO=		M{XhWWlvcGmkaYTpc44hd2ZiQYXyc5JiKEJia3nuZZNmKGmwIHj1cYFvKEinTHGgT5lwfG9iY3XscJMh[XO\|ZYPz[YQh[XNiZX\m[YN1KG:wIHTpd5RzcWK3dHnvckBw\iCyaIPwbI8ucGm\|dH;u[UBJOyC\|ZYKxNEBt\X[nbDDpcoN2[mG2ZXSg[o9zKDJyIHjyd{whUUN3MDC9JFAvODBzNTFOwG0v	NEi2bXI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{O5NVE{Oyd-MkezPVEyOzN:L3G+
HeLa Kyoto	NEjo[XhHfW6ldHnvckBie3OjeR?=		M4\tSFIxKGi{cx?=		MV;Jcohq[mm2aX;uJI9nKEG3cn;yZUBCKGurbnHz[UBifXSxcHjvd5Bpd3K7bHH0bY9vKGG2IGTodlI5QCCrbjDoeY1idiCKZVzhJGt6d3SxIHPlcIx{KGmwY4XiZZRm\CCob4KgNlAhcHK\|LDDJR\|UxKD1iMD6wNFY4KM7:TT6=	Mn3QQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd\|OUGxN\|MoRjJ5M{mxNVM{RC:jPh?=
multiple myeloma	MlHqSpVv[3Srb36gZZN{[Xl?				NULvNXpMW3WycILld5Nqd25ib3[gZ4VtdCCvaYTvd4l{KGmwIHj1cYFvKG23bITpdIxmKG27ZXzvcYEh[2WubIOsJGlEPTBiPTCwMlAxOyEQvF2u	M3flSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6OUG4NFk3Lz5{OEmxPFA6PjxxYU6=
Calu6	M{jP[mFvfGm2dX3vdkBie3OjeR?=	MmfoNlAhdWdxa3e=	NELuWWwzOSCmYYnz		MXXBcpRqfHWvb4KgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCFYXz1OkBk\WyuczD4[Y5w\3KjZoTl[EBqdiCvb4Xz[UBie3Onc4Pl[EBieyC2dX3vdkBoem:5dHigbY5pcWKrdHnvckBifCB{MDDt[{9s\yxicH:gZollKGGmbXnubZN1\XKnZDDmc5IhOjFiZHH5dy=>	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjFyMUW2OEc,OjZzMEG1OlQ9N2F-
HeLa Kyoto	M3;LV2Z2dmO2aX;uJIF{e2G7	NVrKd\|JbOC5{NTD1US=>	M1jU[VIxKGi{cx?=		M3npVGlvcGmkaYTpc44hd2ZiQYXyc5JiKEFia3nuZZNmKGyxY3HsbZpifGmxbjDheEB{eGmwZHzlJI1q[3KxdIXieYxmeyCrbjDoeY1idiCKZVzhJGt6d3SxIHPlcIx{KGG2IECuNlUhfU1iaX7jeYJifGWmIH\vdkAzOCCqcoO=	MnXiQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjd\|OUGxN\|MoRjJ5M{mxNVM{RC:jPh?=
MDA-MB-231	NEPUcG5HfW6ldHnvckBie3OjeR?=	NH\1TFQyKHWP	NFPKem81QCCqcoO=		M2HTcGlv\HWldHnvckBw\iClaILvcY9{d22nIHHsbYdvdWWwdDDk[YZm[3S\|IHnuJIh2dWGwIF3ERU1OSi1{M{GgZ4VtdHNiYYSgNUB2VSCjZoTldkA1QCCqcoOgZpkhTEGSSTDzeIFqdmmwZzDiZZNm\CCrbX31co9ndHWxcnXzZ4Vv[2ViYYPzZZk>	MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTN3OEG0O{c,Ojl\|NUixOFc9N2F-
MDA-MB-231	M4\iO2Z2dmO2aX;uJIF{e2G7	Mon6NUB2VQ>?	M1S0XlQ5KGi{cx?=		MVrJcoR2[3Srb36gc4Yh[WKncoLhcpQhe3CrbnTs[UBnd3KvYYTpc44hf2m2aDD0dolxd2yjcjDhcoQhfGW2cnHwc4xieiCxY3P1dpJmdmOnIHnuJIh2dWGwIF3ERU1OSi1{M{GgZ4VtdHNiYYSgNUB2VSCjZoTldkA1QCCqcoOgZpkhTEGSSTDzeIFqdmmwZzDiZZNm\CCrbX31co9ndHWxcnXzZ4Vv[2ViYYPzZZk>	NYT4RWJTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmzOVgyPDdpPkK5N\|U5OTR5PD;hQi=>
MDA-MB-231	MlTiSpVv[3Srb36gZZN{[Xl?	MknJNE42KHWP	MX60PEBpenN?		M3LQbGlvcGmkaYTpc44hd2ZiYXzwbIEufHWkdXzpckBqdiCqdX3hckBOTEFvTVKtNlMyKGOnbHzzJIF{e2W\|c3XkJIF{KGGkb3zpd4hu\W62IH;mJJJm\3WuYYKgcI9k[XSrb36gc4YheHKxdHXpckBifCByLkWgeW0h[W[2ZYKgOFghcHK\|IHL5JGRCWElic4ThbY5qdmdiYnHz[YQhcW2vdX7v[ox2d3Knc3PlcoNmKGG\|c3H5	MoL3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl\|NUixOFcoRjJ7M{W4NVQ4RC:jPh?=
MDA-MB-231	NWLZVm1STnWwY4Tpc44h[XO\|YYm=	NE\xUnYxNjVidV2=	NWjKcJVvPDhiaILz		NFjmTohKdmirYnn0bY9vKG:oIFHVVmtCKGmwIHj1cYFvKE2GQT3NRk0zOzFiY3XscJMh[XO\|ZYPz[YQh[XNiYXLvcIl{cG2nboSgc4YhemWpdXzhdkBtd2OjdHnvckBw\iCycn;0[YlvKGG2IECuOUB2VSCjZoTldkA1QCCqcoOgZpkhTEGSSTDzeIFqdmmwZzDiZZNm\CCrbX31co9ndHWxcnXzZ4Vv[2ViYYPzZZk>	NFvuXnA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUO1PFE1Pyd-MkmzOVgyPDd:L3G+
TC32	MYPxTHRUKGG\|c3H5				MX;xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhXEN\|MjDj[Yxtew>?	NYHobXBNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Saos-2	NXHJdJlSeUiWUzDhd5NigQ>?				NGr1U\|FyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU3Hvd{0zKGOnbHzz	M{TlPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-SH	NE\iXGZyUFSVIHHzd4F6				NXfPZ253eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPLMW4uW0hiY3XscJM>	NVPYN2xYRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
MG 63 (6-TG R)	NG\pUVdyUFSVIHHzd4F6				MY\xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVUdiNkOgLFYuXEdiUjmgZ4VtdHN?	M1HVS\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
NB1643	NGPqUJJyUFSVIHHzd4F6				MkH1dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6EMU[0N{Bk\Wyucx?=	NFrFc3k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB-EBc1	MWXxTHRUKGG\|c3H5				NVjSVWVCeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhVkJvRVLjNUBk\Wyucx?=	Mm\yQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
MG 63 (6-TG R)	MYnxTHRUKGG\|c3H5				NYH4N3JleUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhVUdiNkOgLFYuXEdiUjmgZ4VtdHN?	NVrZfJo6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
U-2 OS	MYjxTHRUKGG\|c3H5				M2rXOJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHUuOiCRUzDj[Yxtew>?	MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SJ-GBM2	M3;PdJFJXFNiYYPzZZk>				MVPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0pvR1LNNkBk\Wyucx?=	MoDJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-MC	M4jhXpFJXFNiYYPzZZk>				NYPCWno1eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPLMW4uVUNiY3XscJM>	MoTiQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
NB-EBc1	NGHaVlVyUFSVIHHzd4F6				NY\UfI55eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF7CMWVD[zFiY3XscJM>	NFvBTXQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
LAN-5	M2DkdpFJXFNiYYPzZZk>				Mn\ZdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEyDTj21JINmdGy\|	MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Rh18	MX7xTHRUKGG\|c3H5				NIiwZpRyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUnixPEBk\Wyucx?=	Ml3vQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-MC	M2\WSpFJXFNiYYPzZZk>				MWPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDTT{1PNU2FIHPlcIx{	MmX5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
TC32	M3TCS5FJXFNiYYPzZZk>				M{DibJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHREOzJiY3XscJM>	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Saos-2	NGjzd5dyUFSVIHHzd4F6				M1XzRpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHNid3NvMjDj[Yxtew>?	MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	p-AURKA(T288) / p-EIF4E(S209) / c-Myc; PubMed: 28073841 Clin Cancer Res Inhibition of AURKA with alisertib downregulated p-EIF4E (S209) and c-MYC protein levels as assayed by Western blotting. phospho-Aurora A / Aurora B; PubMed: 22863010 Cell MLN8237differentially inhibited phosphorylation of Aurora kinases. CMK cells were incubated with 0.1 µM paclitaxel for 18 hr, then DMSO or MLN8237 was added and incubated for 2 hr. The degree of phosphorylation of the Aurora kinases in each sample was determined by Western blot. H3S10P / H3K27me2 / H3K27me3 / H3K9me2 / H3AcK / H4K16Ac; PubMed: 29477140 Mol Cells THP-1 cells were treated with alisertib or DMSO for 48 h. The levels of histone modifications were detected by western blot analysis with the indicated antibodies. H3 was used as a loading control.	28073841 22863010 29477140
Growth inhibition assay	Cell viability; PubMed: 25632225 Drug Des Devel Ther PANC-1 and BxPC-3 cells were treated with ALS at concentrations ranging from 0.1 μM to 50 μM for 24 hours. The viability of PANC-1 and BxPC-3 cells determined by MTT assay. ALS, alisertib.	25632225
Immunofluorescence	acetylated α-tubulin / γ-tubulin; PubMed: 29401581 FASEB J Representative immunofluorescence (IF) image and graph in human PKD1-mutant WT9-7, WT9-12 cells or hTERT-RPE1 (RPE1) cells after 2 hours treatment with vehicle, ganetespib , or alisertib to inhibit AURKA, or combination of alisertib and ganetespib. acetylated α-tubulin (red); γ-tubulin (green); DAPI (blue). Scale bars, 5 μm. E-cadherin / β-catenin / vimentin / p-SMAD5; PubMed: 23334326 Oncogene Immunofluorescence analysis of CD24 (-/low) cells treated with1 μM MLN8237 for 48 and 72 h showing reversion of EMT. E-cadherin and p-SMAD5 were labeled in red, β-catenin and vimentin were labeled in green, and DNA was labeled in blue with Hoechst dye. Centrin-2 / tubulin; PubMed: 30899434 Oncotarget Following inhibition of Aurora A kinase activity with 100 nM alisertib, cells with two or excess centrosomes similarly exhibit disorganized mitotic spindles. Cells with extra centrosomes are efficiently clustered into bipolar spindles prior to anaphase onset while those with supernumerary centrosomes undergo multipolar mitoses. Centrin-2, a marker of centrioles is shown in green, tubulin in red, and chromatin in blue. AurA inhibitor: alisertib. phospho-Aurora A(T288); PubMed: 20382844 Blood MM1.S cells were treated with DMSO or MLN8237 (0.5μM) for 24 hours and then stained with anti-phospho (Thr288)-Aurora-A kinase antibody (red), αtubulin (green), and DNA (blue). Overlapping localization is shown in the merged images. Arrow indicates Aurora-A autophosphorylation on Thr288 in the centrosome (original magnification ×40). Magnified single mitotic cell image is shown in the right panel.	29401581 23334326 30899434 20382844

In vivo

MLN8237 significantly reduces the tumor burden with tumor growth inhibition (TGI) of 42% and 80% at 15 mg/kg and 30 mg/kg, respectively, and prolongs the survival of mice compared with the control. ^[2]

Protocol

Kinase Assay:^[1]	- Collapse Aurora A radioactive Flashplate enzyme assay: Aurora A radioactive Flashplate enzyme assay is conducted to determine the nature and degree of MLN8237-mediated inhibition in vitro. Recombinant Aurora A is expressed in Sf9 cells and purified with GST affinity chromatography. The peptide substrate for Aurora A is conjugated with biotin (Biotin-GLRRASLG). Aurora A kinase (5 nM) is assayed in 50 mM Hepes (pH 7.5), 10 mM MgCl₂, 5 mM DTT, 0.05% Tween 20, 2 μM peptide substrate, 3.3 μCi/mL [γ-³³P]ATP at 2 μM, and increasing concentrations of MLN8237 by using Image FlashPlates.
Cell Research:^[2]	- Collapse Cell lines: MM1.S, MM.1R, LR5, RPMI 8226, DOX40, OPM1, OPM2, INA6, and U266 Concentrations: Dissolved in DMSO, final concentrations ~10 μM Incubation Time: 24, 48, and 72 hours Method: Cells are exposed to various concentrations of MLN8237 for 24, 48, and 72 hours. Cells viability is measured using MTT assay, and cell proliferation is measured using ³[H]-thymidine incorporation. For cell cycle analysis, cells are permeabilized by 70% ethanol at -20 °C, and incubated with 50 μg/mL PI and 20 units/mL RNase-A. DNA content is analyzed by flow cytometry using BDFACS-Canto II and FlowJo software. For the detection of apoptosis and senescence, cells are stained with fluorescein isothiocyanate-annexin V and PI. Apoptotic cells are determined by flow cytometric analysis using BDFACS-Canto II and FlowJo software. (Only for Reference)
Animal Research:^[2]	- Collapse Animal Models: Severe combined immune-deficient (SCID) mice inoculated subcutaneously with MM1.S cells Dosages: ~30 mg/kg/day Administration: Orally (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	27 mg/mL (52.03 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 5%DMSO+30% PEG300+5%Tween-80+ddH2O For best results, use promptly after mixing.	6mg/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 Alisertib (MLN8237) SDF

Molecular Weight	518.92
Formula	C₂₇H₂₀ClFN₄O₄
CAS No.	1028486-01-2
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	COC1=C(C(=CC=C1)F)C2=NCC3=CN=C(N=C3C4=C2C=C(C=C4)Cl)NC5=CC(=C(C=C5)C(=O)O)OC

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

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

Note：1.Please make sure the liquid is clear before adding the next solvent.
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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2021-05-17)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04479306	Recruiting	Drug: Alisertib\|Drug: Osimertinib\|Drug: Sapanisertib	Recurrent Lung Non-Small Cell Carcinoma\|Stage IIIB Lung Cancer AJCC v8\|Stage IV Lung Cancer AJCC v8\|Stage IVA Lung Cancer AJCC v8\|Stage IVB Lung Cancer AJCC v8	M.D. Anderson Cancer Center	June 18 2020	Phase 1
NCT02812056	Withdrawn	Drug: Alisertib\|Drug: TAK-228	Malignant Neoplasms of Digestive Organs\|Malignant Neoplasms of Female Genital Organs\|Malignant Neoplasms of Lip Oral Cavity and Pharynx\|Malignant Neoplasms of Male Genital Organs	M.D. Anderson Cancer Center\|Millennium Pharmaceuticals Inc.	September 2016	Phase 1
NCT02719691	Active not recruiting	Drug: Alisertib\|Drug: MLN0128	Metastatic Breast Cancer\|Solid Tumors	University of Colorado Denver	May 13 2016	Phase 1
NCT02367352	Terminated	Drug: Alisertib\|Drug: Paclitaxel	Advanced Solid Tumors\|Ovarian Cancer\|Small Cell Lung Cancer	Millennium Pharmaceuticals Inc.\|Takeda	March 19 2015	Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Frequently Asked Questions

Question 1:
What is the suggested formulation of this compound for mouse injection(i.p.)?
Answer:
It can be dissolved in 6% DMSO/50% PEG 300/5% Tween 80/ddH2O at 10 mg/ml as a clear solution.

Aurora Kinase Signaling Pathway Map

Aurora Kinase Inhibitors with Unique Features

Pan Aurora Kinase Inhibitor

Danusertib (PHA-739358) : Pan-Aurora kinase inhibitor, Aurora A/B/C, IC50=13 nM/79 nM/61 nM.
Pan Aurora Kinase Inhibitor

SNS-314 Mesylate : Pan-Aurora kinase inhibitor, Aurora A/B/C, IC50=9 nM/31 nM/3 nM.
Most Potent Aurora Kinase Inhibitor

MK-5108 (VX-689) : Aurora A, IC50=0.064 nM.
Aurora Kinase Inhibitor in Clinical Trial

VX-680 (Tozasertib, MK-0457) : Phase II for Advanced Non-Small Cell Lung Cancer (NSCLC).
Classic Aurora Kinase Inhibitor

Hesperadin : Potently inhibits Aurora B with IC50 of 250 nM.

Related Aurora Kinase Products

Ro-3306 ^New

RO-3306 is an ATP-competitive, and selective CDK1 inhibitor with K_i of 20 nM, >15-fold selectivity against a diverse panel of human kinases. RO-3306 enhances p53-mediated Bax activation and mitochondrial apoptosis.
ML141 ^New

ML141 (CID-2950007) is demonstrated to be a potent, selective and reversible non-competitive inhibitor of Cdc42 GTPase suitable for in vitro assays, with IC50 of 200 nM and selectivity against other members of the Rho family of GTPases (Rac1, Rab2, Rab7). ML141 is associated with an increase in p38 activation and may induce p38-dependent apoptosis/senescence. ML141 also protects neuroblastoma cells from metformin-induced apoptosis.
Salirasib ^New

Salirasib (Farnesylthiosalicylic acid, FTS) is a potent competitive prenylated protein methyltransferase (PPMTase) inhibitor with K_i of 2.6 μM, which inhibits _Ras methylation. Salirasib exerts antitumor effects and induces autophagy. Salirasib exerts antitumor effects and induces autophagy. Phase 2.
Barasertib (AZD1152-HQPA)

Barasertib (AZD1152-HQPA, AZD2811, INH-34) is a highly selective Aurora B inhibitor with IC50 of 0.37 nM in a cell-free assay, ~3700 fold more selective for Aurora B over Aurora A. Phase 1.
Tozasertib (VX-680, MK-0457)

Tozasertib (VX-680, MK-0457) is a pan-Aurora inhibitor, mostly against Aurora A with K_i_app of 0.6 nM in a cell-free assay, less potent towards Aurora B/Aurora C and 100-fold more selective for Aurora A than 55 other kinases. The only exceptions are Fms-related tyrosine kinase-3 (FLT-3) and BCR-ABL tyrosine kinase, which are inhibited by the Tozasertib with both Ki of 30 nM. Tozasertib induces apoptosis and autophagy. Phase 2.
Danusertib (PHA-739358)

Danusertib (PHA-739358) is an Aurora kinase inhibitor for Aurora A/B/C with IC50 of 13 nM/79 nM/61 nM in cell-free assays, modestly potent to Abl, TrkA, c-RET and FGFR1, and less potent to Lck, VEGFR2/3, c-Kit, CDK2, etc. Danusertib induces apoptosis, cell cycle arrest, and autophagy. Phase 2.
ZM 447439

ZM 447439 is a selective and ATP-competitive inhibitor for Aurora A and Aurora B with IC50 of 110 nM and 130 nM, respectively. It is more than 8-fold selective for Aurora A/B than MEK1, Src, Lck and has little effect against CDK1/2/4, Plk1, Chk1, etc.

Features:An Aurora selective ATP-competitive inhibitor.
MLN8054

MLN8054 is a potent and selective inhibitor of Aurora A with IC50 of 4 nM in Sf9 insect cell. It is more than 40-fold selective for Aurora A than Aurora B. Phase 1.
MK-5108 (VX-689)

MK-5108 (VX-689) is a highly selective Aurora A inhibitor with IC50 of 0.064 nM in a cell-free assay and is 220- and 190-fold more selective for Aurora A than Aurora B/C, while it inhibits TrkA with less than 100-fold selectivity. MK-5108 (VX-689) induces autophagy. Phase 1.
Aurora A Inhibitor I (TC-S 7010)

Aurora A Inhibitor I (TC-S 7010) is a novel, potent, and selective inhibitor of Aurora A with IC50 of 3.4 nM in a cell-free assay. It is 1000-fold more selective for Aurora A than Aurora B. Aurora A Inhibitor I (TC-S 7010) triggers apoptosis through the ROS-mediated UPR signaling pathway.

Features:Aurora A Inhibitor I is a novel, potent, and selective inhibitor to Aurora A.

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Alisertib (MLN8237)