Buparlisib (BKM120)

Name: Buparlisib (BKM120)
Brand: Selleck Chemicals
SKU: S2247
Rating: 5 (202 reviews)

For research use only.

Catalog No.S2247 Synonyms: NVP-BKM120

202 publications

CAS No. 944396-07-0

Buparlisib (BKM120, NVP-BKM120) is a selective PI3K inhibitor of p110α/β/δ/γ with IC50 of 52 nM/166 nM/116 nM/262 nM in cell-free assays, respectively. Reduced potency against VPS34, mTOR, DNAPK, with little activity to PI4Kβ. Buparlisib induces apoptosis. Phase 2.

Selleck's Buparlisib (BKM120) has been cited by 202 publications

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Nat Immunol, 2020, 21(4):442-454

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Science, 2019, 364(6441)

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Cancer Cell, 2018, 34(6):922-938

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Cancer Cell, 2018, 33(1):91-107

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Cell, 2017, 161(4):803-16

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Cancer Discov, 2017, 7(9):1018-1029

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Nature, 2016, 529(7586):413-417

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Nat Med, 2015, 10.1038/nm.3855

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Nat Med, 2015, 21(9):1038-47

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Cancer Discov, 2014, 4(1):69-79

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Cell, 2012, 27;149(3):656-70.

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Nat Med, 2012, 18(6):892-901

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Cancer Cell, 2012, 21(2):155-67

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Nat Commun, 2021, 12(1):1920

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Theranostics, 2021, 11(8):3552-3564

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Cell Death Dis, 2021, 12(1):108

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Cancer Cell Int, 2021, 21(1):24

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Cell Biol Int, 2021, 10.1002/cbin.11557

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Oncotarget, 2021, 12(7):674-685

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

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Cell Rep, 2020, 31(12):107800

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Sci Signal, 2020, 3;13(621) pii: eaax2364

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Cancers (Basel), 2020, 12(9)E2500

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Br J Cancer, 2020, 10.1038/s41416-020-01074-2

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Am J Cancer Res, 2020, 10(11):3765-3783

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Mol Cancer Res, 2020, 11

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Sci Rep, 2020, 10(1):16208

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Front Neurosci, 2020, 2;14:223

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Eur J Pharmacol, 2020, 870:172821

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Cell Biol Int, 2020, 10.1002/cbin.11322

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Turk J Haematol, 2020, 37(3):167-176

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Genes Cancer, 2020, 11(3-4):106-121

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BMC Cancer, 2020, 20(1):724

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FASEB Bioadv, 2020, 2(2):126-144

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Commun Biol, 2020, 3(1):593

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NPJ Breast Cancer, 2020, 6:30

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Mol Oncol, 2020, 10.1002/1878-0261.12673

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Cancer, 2020, 10.1002/cncr.33071

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Small GTPases, 2020, 10.1080/21541248

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Nat Cell Biol, 2019, 21(2):226-237

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Nat Commun, 2019, 10(1):259

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Nat Commun, 2019, 10(1):1515

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J Thorac Oncol, 2019, 14(6):1061-1076

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Leukemia, 2019, 10.1038/s41375-019-0556-z

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Cell Syst, 2019, 8(2):97-108

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Theranostics, 2019, 9(8):2380-2394

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Cell Rep, 2019, 27(1):294-306

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Cell Rep, 2019, 27(2):631-647

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Cell Rep, 2019, 28(9):2317-2330

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Cell Death Differ, 2019, 10.1038/s41418-019-0422-6

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Cancer Lett, 2019, 466:23-34

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Cancers (Basel), 2019, 11(1)E37

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Cancers (Basel), 2019, 11(2)

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Mol Ther Oncolytics, 2019, 13:58-66

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Cancer Discov, 2019, 9(9):1306-1323

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Mol Cancer Ther, 2019, 18(4):834-844

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Aging (Albany NY), 2019, 11(18):7780-7795

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Am J Cancer Res, 2019, 9(12):2774-2788

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J Cell Physiol, 2019, 234(7):10907-10917

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Front Oncol, 2019, 0.87569444444

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Front Oncol, 2019, 9:1119

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Eur J Immunol, 2019, doi: 101002/eji201948241

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

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Biochem J, 2019, 476(23):3583-3593

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Prostate, 2019, 79(11):1347-1359

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Chem Biol Interact, 2019, 302:101-107

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Eur J Pharmacol, 2019, 842:89-98

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Biochem Biophys Res Commun, 2019, 513(3):546-552

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Leuk Lymphoma, 2019, 10.1080/10428194.2019.1594211

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Int J Hematol, 2019, 110(2):213-227

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Oncol Lett, 2019, 17(3-:3151-3162

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Oncol Lett, 2019, 18(6):6249-6260

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NPJ Breast Cancer, 2019, 05:31

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

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Nat Biomed Eng, 2018, 2(4):239-253

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Nat Protoc, 2018, 13(12):2827-2843

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Nat Commun, 2018, 9(1):4550

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Nat Commun, 2018, 9(1):1357

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EMBO Mol Med, 2018, 10(5)

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Cancer Res, 2018, 78(8):2000-2013

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Cancer Res, 2018, 78(9):2383-2395

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NPJ Genom Med, 2018, 3:15

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Cancer Res, 2018, 78(14):4007-4021

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Cell Rep, 2018, 24(8):2155-2166

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Elife, 2018, 7e33718

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Int J Cancer, 2018, 143(5):1188-1201

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Oncogene, 2018, 37(3):363-376

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Cancer Lett, 2018, 439:56-65

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Sci Signal, 2018,

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Oncol Rep, 2018, 40(6):3223-3234

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PLoS One, 2018, 13(2):e0191890

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Oncol Lett, 2018, 15(3):3321-3328

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NPJ Breast Cancer, 2018, 4:36

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Oncotarget, 2018, 9(56):30869-30882

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J Exp Med, 2018, 215(1):159-175

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Mol Cell, 2017, 67(3):512-527

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Mol Cell, 2017, 65(6):999-1013

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Nat Commun, 2017, 8:15623

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Nat Commun, 2017, 8;8:15617

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Nat Commun, 2017, 8:15021

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Nat Commun, 2017, 8(1):1278

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Dev Cell, 2017, 43(6):673-688

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Proc Natl Acad Sci U S A, 2017, 114(41):E8628-E8636

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Cancer Res, 2017, 77(16):4448-4459

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Mol Cancer Ther, 2017, 16(4):729-738

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Mol Cancer Ther, 2017, 10.1158/1535-7163

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Mol Cancer Ther, 2017, 16(9):1779-1790

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Mol Cell Proteomics, 2017, 16(10):1864-1888

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BMC Cancer, 2017,

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SLAS Discov, 2017, 22(8):974-984

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Oncotarget, 2017,

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Oncotarget, 2017, 8(5):7878-7890

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Cell Stem Cell, 2017, 20(2):233-246

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Nat Cell Biol, 2016, 18(12):1324-1335

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

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Genome Biol, 2016, 17:80

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Clin Cancer Res, 2016, 22(3):644-56.

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PLoS Biol, 2016, 14(11):e1002581

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Cancer Res, 2016, 76(24):7168-7180

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Cell Rep, 2016,

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J Hematol Oncol, 2016, 9(1):113

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Cancer Discov, 2016, 6(10):1134-1147

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J Transl Med, 2016, 14:56

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Int J Biochem Cell Biol, 2016, 79:308-317

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PLoS One, 2016, 11(1):e0147682

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PLoS One, 2016, 10.1371/journal

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Oncotarget, 2016, 7(41):67277-67287

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Nature, 2016, 529(7586):413-417

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

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Oncotarget, 2016,

PubMed: 27153554 ( click the link to review the publication )

Sci Rep, 2016, 6:20189

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Oncotarget, 2016, 7(45):72608-72621

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J Clin Invest, 2015, 10.1172/JCI78018

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J Clin Invest, 2015, 125(12):4559-71

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Genes Dev, 2015, 29(16):1677-82

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Proc Natl Acad Sci U S A, 2015, 112(28):8638-43

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Cancer Res, 2015, 75(14):2851-62

PubMed: 25977330 ( click the link to review the publication )

Oncogene, 2015, 10.1038/onc.2015.173

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Glia, 2015, 63(10):1850-9

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Cancer Discov, 2015, 5(11):1194-209

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Gynecol Oncol, 2015, 138(1):165-73

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Biomed Pharmacother, 2015, 75:40-50

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Acta Pharmacol Sin, 2015, 10.1038/aps.2015.4

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Cell Signal, 2015, 27(12):2389-400

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Exp Cell Res, 2015, 332(2):223-35

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Exp Cell Res, 2015, 332(2):223-35

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Int J Biochem Cell Biol, 2015, 60C:34-42

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Int Immunopharmacol, 2015, 28(1):675-85

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PLoS One, 2015, 10(9):e0133610

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PLoS One, 2015, 10(4):e0123410

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Immunol Res, 2015, 10.1007/s12026-015-8648-y

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Oncotarget, 2015, 6(12):10399-414

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Oncotarget, 2015, 6(31):31792-804

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Crit Rev Oncol Hematol, 2015,

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J Clin Invest, 2014, 124(12):5490-502

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J Clin Invest, 2014, 124(11):4737-52

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J Exp Med, 2014, 211(13):2497-2505

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Cancer Res, 2014, 10.1158/0008-5472.CAN-14-1392

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Cell Rep, 2014, 8(5):1265-70

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Oncogene, 2014, 10.1038/onc.2014.328

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PLoS Pathog, 2014, 10(6):e1004196

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Breast Cancer Res, 2014, 16(1):R9

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Breast Cancer Res, 2014, 16(4):406

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Cell Death Dis, 2014, 5:e1134

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Cell Death Dis, 2014, 5:e1013

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

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Mol Cancer Res, 2014, 12(10):1520-31

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J Biol Chem, 2014, 289(33):22785-97

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PLoS One, 2014, 9(10):e108780

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PLoS One, 2014, 9(7):e101969

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Biochem Biophys Res Commun, 2014, 10.1016/j.bbrc.2014.09.129

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Oncotarget, 2014, 5(14):5295-303

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Assay Drug Dev Technol, 2014, 12(9-10):514-26

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Clin Cancer Res, 2013, 19(21):5940-51

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Cancer Res, 2013, 73(17):5459-72

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Oncogene, 2013, 10.1038/onc.2013.509

PubMed: 24292683 ( click the link to review the publication )

Breast Cancer Res, 2013, 15(4):R55

PubMed: 23844554 ( click the link to review the publication )

Cell Commun Signal, 2013, 11(1):3

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Mol Cancer Res, 2013, 11(10):1269-78

PubMed: 23814023 ( click the link to review the publication )

BMC Cancer, 2013, 13:465

PubMed: 24103747 ( click the link to review the publication )

Cancer Chemother Pharmacol, 2013, 71(5):1297-307

PubMed: 23479136 ( click the link to review the publication )

University Gattingen, 2013, Elisabeth Hand

PubMed: ( click the link to review the publication )

Purity & Quality Control

Choose Selective PI3K Inhibitors

Biological Activity

Description

Targets

p110α ^[1] (Cell-free assay)	p110δ ^[1] (Cell-free assay)	p110β ^[1] (Cell-free assay)	p110γ ^[1] (Cell-free assay)	Vps34 ^[1] (Cell-free assay)	View More
52 nM	116 nM	166 nM	262 nM	2.4 μM	View More

In vitro

BKM120 is not sensitive to Class III and Class IV PI3K's or PI4K. NVP-BKM120 shows great antiproliferation activity to PI3K deregulated cell lines including A2780, U87MG, MCF7 and DU145 with GI50 of 0.1-0.7 nM. ^[1] BKM120 induces multiple myeloma cells (ARP1, ARK, MM.1S, MM1.R and U266) apoptosis, which results in increased G1-phase cells and decreased S-phase cells. BKM120 induced CD138+ primary MM cell apoptosis and has significant lower cytotoxicity toward CD138− stromal cells. BKM120 exposure could cause upregulation of BimS and downregulation of XIAP. ^[2] BKM120 demonstrates antiproliferative activity in human gastric cancer cell lines by decreasing mTOR downstream signaling. BKM120 could increase either p-ERK or p-STAT3 in KRAS mutant gastric cancer cells. Combination with STAT3 blockade, BKM120 shows a synergism in cells harboring mutated KRAS by inducing apoptosis, but not in KRAS wild-type cells. ^[3] A recent study shows that BKM120 shows differential forms of cell death on the basis of p53 status of the cells with p53 wild-type cells undergoing apoptotic cell death and p53 mutant/deleted cells having a mitotic catastrophe cell death. BKM120 mediates mitotic catastrophe mainly through Aurora B kinase. ^[4]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
glioma cell lines	NXu2fmJ7T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		M3XiNVczcA>?		M4TtcWlEPTB;MT2y{txO	MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjB4NUC4NEc,OjJyNkWwPFA9N2F-
U87	MmXGRZBweHSxc3nzJGF{e2G7	MUmy{txO	Ml;VO\|Jp		M{TVWIlv\HWlZYOgZ4VtdCCjcH;weI9{cXNiYX7kJINt\WG4ZXSgVGFTWCCjbnSgZ4F{eGG\|ZT2z	NGfU[Ys9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkC2OVA5OCd-MkKwOlUxQDB:L3G+
SNU-601	Mon5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		MVe3Nog>	MkLuSG1UVw>?	MYDJR\|UxRTBwOEG2xtExNjB4M988US=>	M1PsO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MUW5PFE1Lz5{MkG1PVgyPDxxYU6=
SNU-1	MoHiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		NVTEdmdSPzKq	MYnEUXNQ	NHT1WoNKSzVyPUGuNFgzyrFyLkCyPO69VQ>?	MlvoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzNUm4NVQoRjJ{MUW5PFE1RC:jPh?=
SNU-668	Mn3sS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		NUPMOZdyPzKq	NHjqe3pFVVOR	MlezTWM2OD1zLkW3PeKyOC5yN{VOwG0>	MmnlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzNUm4NVQoRjJ{MUW5PFE1RC:jPh?=
AGS	MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		M1uwdFczcA>?	M3yzW2ROW09?	MkT3TWM2OD1zLkexOOKyOC5zMUhOwG0>	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF3OUixOEc,OjJzNUm4NVQ9N2F-
SNU-216	NYrBOYxFT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		NFvaXFM4Omh?	MXTEUXNQ	M4HJT2lEPTB;Mj62PVLDuTBwMEiy{txO	MkPZQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzNUm4NVQoRjJ{MUW5PFE1RC:jPh?=
SNU-5	NHTaVFJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		NXmxW5ZkPzKq	M{DxT2ROW09?	M3vWPGlEPTB;MT6zOVHDuTBwMEmx{txO	NH3CTpA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkG1PVgyPCd-MkKxOVk5OTR:L3G+
SNU-638	MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		NFnlW2I4Omh?	M4O5O2ROW09?	MX\JR\|UxRTJwMkiyxtExNjB3M988US=>	MoPtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzNUm4NVQoRjJ{MUW5PFE1RC:jPh?=
SNU-16	MlnXS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		MXq3Nog>	NELndI1FVVOR	MkHrTWM2OD1zLkW3N:KyOC5yMEJOwG0>	NVLo[od2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKxOVk5OTRpPkKyNVU6QDF2PD;hQi=>
SNU-484	M2PWU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7		M2\pblczcA>?	MnfrSG1UVw>?	NGnmSW1KSzVyPUGuO\|I5yrFyLkC0Oe69VQ>?	M3zKSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MUW5PFE1Lz5{MkG1PVgyPDxxYU6=
SNU-620	NWfJRpU6T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		MV23Nog>	M3HqPGROW09?	NGTZR\|JKSzVyPUKuPVM6yrFyLkCwNe69VQ>?	NHWyOmo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkG1PVgyPCd-MkKxOVk5OTR:L3G+
SNU-719	NFvPPINIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		M{f1S\|czcA>?	MkfNSG1UVw>?	M2TmSWlEPTB;Mz6wN\|fDuTBwMEOy{txO	NFrEd2I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkG1PVgyPCd-MkKxOVk5OTR:L3G+
MM cell lines	NXvpcI5OT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NFTDSZYyOM7:TR?=	M37IelI1cA>?	M1\sdmROW09?	MlHITWM2OCC4YYLp[ZMh[W2xbneg[Iln\mW{ZX70JINmdGxibHnu[ZMhcW5idHnt[UBidmRiZH;z[UBl\XCnbnTlcoNm	NFrPWYI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkKwO\|Q5PSd-MkKyNFc1QDV:L3G+
ARP-1	NFLNUJFCeG:ydH;zbZMhSXO\|YYm=	NHGwVoMyOM7:TR?=	NIH6VWozPGh?	MkLUSG1UVw>?	M1X1Volv\HWlZYOgUW0h[2WubDDhdI9xfG:\|aYOgeIhzd3WpaDDjZZNx[XOnIHHjeIl3[XSrb36=	NHHvWZY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkKwO\|Q5PSd-MkKyNFc1QDV:L3G+
colon cancer cell lines	M3:5UGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NYXuNYtyOC1zMN88US=>	NH;NeFY4Omh?	M3rLdmROW09?	MYfJR\|UxRTIQvF2=	NHv5SWM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkW0N\|g2Pyd-MkK1OFM5PTd:L3G+
gastric cancer cell lines	M{HT[Wdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M{TVdVAuOTEQvF2=	MoXwO\|Jp	NE\YOnJFVVOR	NY[wPVV7UUN3ME2yMVXPxE1?	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjV2M{i1O{c,OjJ3NEO4OVc9N2F-
HCT-116/HT-29/MKN-45	NYLDO2hESXCxcITvd4l{KEG\|c3H5	MlXDNu69VQ>?	M4DTdFQ5cA>?		Morrd4hq\nRiaX6gS\|IheGijc3W=	NFPxN\|Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkW0N\|g2Pyd-MkK1OFM5PTd:L3G+
HT-29 and HCT-116	NX6y[lZpS2G\|cHHz[UBie3OjeR?=	MoX4Oe69VQ>?	MlPLNlRp		M2XoSolv\HWlZYOgZ4F{eGG\|ZTDhZ5Rqfmm2eR?=	M{D1RlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{NUSzPFU4Lz5{MkW0N\|g2PzxxYU6=
PIK3CA-mutant MCF7	Mnn2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	M2PmT2dKPTB;MU[wxtE6OW6P78{MUGQ2OD17OEFCtVI4O26P	MXi3Nog>		MmHoS2k2OD1zNkFCtVkydk4xvJzMSFUxRTl6MNMxNlc{dk1?	NUHxU3E2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK2OVM6PjdpPkKyOlU{QTZ5PD;hQi=>
PIK3CA-mutant MCF7	MlTpT4lv[XOnIFHzd4F6	NV7jNIpYUUN3ME2xNVTDuTOwTR?=	NWjJTZJJPzKq		MUTJR\|UxRTFzNNMxN45OKGmwIILl[JVkcW6pIFHreEBxcG:\|cHjvdplt[XSrb36gcIV3\Wy\|	M4TNXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{NkWzPVY4Lz5{Mk[1N\|k3PzxxYU6=
MCF7-myr-Akt	M3LwUmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NXWwcVU1T0l3ME2yPVnDuTZ6bl5vwKxNTDVy78{eNVAtODBybl2=	MXq3Nog>		NGfiOZpIUTVyPUK5PeKyPjiwTf-8kGxFPTExvK6xNEwxODCwTR?=	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjZ3M{m2O{c,OjJ4NUO5Olc9N2F-
Y1 cell line	NY\t[YxST3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MlHoNE4y\|ryPL{JOwG0>	MXyyOIg>	M3TwZWROW09?	NILQc4xqdmirYnn0d{A3OO,:hTDj[YxtKH[rYXLpcIl1gSCrbjDNfYMuW2O2cj30doFve2[nY4Tl[EBk\Wyucx?=	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjZ7MkmwOEc,OjJ4OUK5NFQ9N2F-
human NSCLC	M3P4fmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MWSwMlUuOs7:TR?=	MmLDO\|Jp		NXvUbJdiUUN3ME2x{txO	M2P3UlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{N{ixN\|k{Lz5{Mke4NVM6OzxxYU6=
human NSCLC	M1;2WWtqdmG\|ZTDBd5NigQ>?	MmGxNe69VQ>?	NVfGd4tEOjSq		M3HR[IlvcGmkaYTzJJRp\SCDa4SvcXRQWiC\|aXfuZYxqdmdicHH0bJdigSCjdDCzbEBi\nSncjD0doVifG2nboS=	MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjd6MUO5N{c,OjJ5OEGzPVM9N2F-
JVM2	NHL4[oJEgXSxdH;4bYNqfHliYYPzZZk>	M2\rSFAvOi1{MN88US=>	MWK3Nog>	NIfSc5VFVVOR	NX:0R5Z2UUN3ME2wMlnPxE1?	NW\tVm82RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOyN\|g3OzlpPkKzNlM5PjN7PD;hQi=>
EHEB	M3LMU2N6fG:2b4jpZ4l1gSCjc4PhfS=>	MmL6NE4zNTJyzszN	MUS3Nog>	NILNVpNFVVOR	NGDCOohKSzVyPUCuO:69VQ>?	NEnueJM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{KzPFY{QSd-MkOyN\|g3Ozl:L3G+
MEC2	M4XqOWN6fG:2b4jpZ4l1gSCjc4PhfS=>	M2PwNlAvOi1{MN88US=>	M3H6OVczcA>?	MVLEUXNQ	NYjMN4lQUUN3ME2wMlfPxE1?	NEThZpM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{KzPFY{QSd-MkOyN\|g3Ozl:L3G+
primary B-CLL lymphocytes	NIjUcI1CeG:ydH;zbZMhSXO\|YYm=	M2fRV2lEPTBiZn;yJIVi[2hicILpcYFzgSClZXzsJIxqdmV?	MVKyOIg>	MlrPSG1UVw>?	MYrJR\|Ux97zeM988UUBnd3JiYXzsJJBifGmnboTz	M4j5eFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|MkO4OlM6Lz5{M{KzPFY{QTxxYU6=
primary B-CLL lymphocytes	NXLCfpZuU2mwYYPlJGF{e2G7	Mo\NTWM2OCCob4Kg[YFkcCCycnntZZJ6KGOnbHygcIlv\Q>?	MXSyOIg>		NYXMVnlRcW6qaXLpeJMheDdyU{\LJEYhPEVvQmCxJIV5eHKnc4Ppc44>	NF;qUJo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{KzPFY{QSd-MkOyN\|g3Ozl:L3G+
SK-HEP1	M2Pu[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NXnuPGROOS1{MN88US=>	NUPGTXVnPzKq	MoewSG1UVw>?	M{W1TmlEPTExvKyx{txO	NY\aOoV2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0O\|kyOzZpPkKzOFc6OTN4PD;hQi=>
786-0	MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	Mn71NU0zOM7:TR?=	NYX5VXNuPzKq	M1mzOmROW09?	NHHHXWJKSzVy78{cNe69VQ>?	NX7DZ4FMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0O\|kyOzZpPkKzOFc6OTN4PD;hQi=>
human HCC cell lines	MnjrR4VtdCC4aXHibYxqfHliYYPzZZk>	M2rYfFAvODB3LUJOwG0>	M1;Q[VQ5cA>?		MlH6TWM2OD1zzszN	MkTRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2OEm5PVkoRjJ\|NEi5PVk6RC:jPh?=
Huh7	MYXLbY5ie2ViQYPzZZk>	NWTHeZJ3Oc7:TR?=	MWK0PIg>		MkPvd4lodmoxrJHjZY51dHlicnXkeYNmeyCyaH;zdIhwenmuYYTpc44hd2ZiQXv0	NFLEb\|k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S4PVk6QSd-MkO0PFk6QTl:L3G+
human NSCLC cell lines	NHHiO21CeG:ydH;zbZMhSXO\|YYm=	MVGwMlEzPS12zszN	MnvsNlRp	NE\GfJlFVVOR	NEfWT2JKSzVyczDyZY5o\XNiZoLvcUAxNjRvMt88US=>	MmXBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3NkK0O\|IoRjJ\|NU[yOFczRC:jPh?=
Primary CLL cells	NYHOTlRDSXCxcITvd4l{KEG\|c3H5	MYmxMVEx\|ryP	M1PFOVQ5cA>?		M2TSdIlv\HWlZYOgZZBweHSxc3nzJIlvKEOOTDDj[YxteyCrbnTldIVv\GWwdDDv[kBxem:pbn;zeIlkKG2jcnvldpM>	NGnlOGw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{i1NFgxPyd-MkO4OVA5ODd:L3G+
Primary CLL cells	MXHLbY5ie2ViQYPzZZk>	MlPPNu69VQ>?	NGT1NVA{OG2rbh?=		MUTk[YNz\WG\|ZXSgVGk{UyCjY4Tpeol1gQ>?	M3TNO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OEWwPFA4Lz5{M{i1NFgxPzxxYU6=
Primary CLL cells	NEfWTGZEgXSxdH;4bYMhSXO\|YYm=	M4LHbVLPxE1?	MWqyOIg>		MWTpcoR2[2W\|IHPlcIwh[3m2b4TvfIlkcXS7	NUHCT2hrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO4OVA5ODdpPkKzPFUxQDB5PD;hQi=>
LC-1/SQSF	MmfQSpVv[3Srb36gRZN{[Xl?	NUD1c5FEO87:TR?=	MX6yOIg>	MXfEUXNQ	NUKycGlP\GWlcnXhd4UhVlKIMjDwdo91\WmwIHzleoVt	MoH5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7OECwPVMoRjJ\|OUiwNFk{RC:jPh?=
BCR-ABL	MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M1LDfVAvOjVvMUFOwG0>	MknCOIQ>		NYXwb\|hre2mpbnnmbYNidnSueTDpcohq[mm2IHPlcIwheHKxbHnm[ZJifGmxbh?=	MmPGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR{NES2NVIoRjJ2MkS0OlEzRC:jPh?=
T-ALL	NF7pVXpCeG:ydH;zbZMhSXO\|YYm=	NGq2TYxj\XS5ZXXuJFEvPCCjbnSgOU4{KG2PIHH0JFI1cCCjbnSgNE46KGGwZDC1MlUhdU1iYYSgOFhpKGmwIHTp[oZmemWwdDDj[YxtKGyrbnW=	NHnC[4wzPCCxcjC0PIg>	MYfEUXNQ	Ml2zZYZn\WO2czD0bIUhWEl\|SzDwZZRpf2G7IHnuJHQuSUyOIHPlcIwhdGmwZYO=	MmfSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR\|MUC3N\|YoRjJ2M{GwO\|M3RC:jPh?=
H1975	M3XNS2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M3jPV\|AvOy17LkdOwG0>	M1Gz[VczcA>?	M1XIS2ROW09?	MmXuTWM2OD1zLkO4Oe69VQ>?	MlzFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR\|M{e4OFYoRjJ2M{O3PFQ3RC:jPh?=
H1975	NYWyXnVjSXCxcITvd4l{KEG\|c3H5	NUTxUFllOs7:TR?=	MVyyOIg>	MnvFSG1UVw>?	M4LJV4lv[3KnYYPld{BieG:ydH;zbZMhemG2ZTDzbYdvcW[rY3HueIx6	M2DzflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{O3PFQ3Lz5{NEOzO\|g1PjxxYU6=
BON	NXv1ZodzT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NETUPHIyNTYQvF2=	MkWwO\|Jp		Mni5[IVkemWjc3XzJINmdGxicILvcIln\XKjdHnvci=>	M{Lrc\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NESzOVI{Lz5{NES0N\|UzOzxxYU6=
BON	MXfBdI9xfG:\|aYOgRZN{[Xl?	M2LEelEuPc7:TR?=	NIrxOmEzPGh?		MUTpcoNz\WG\|ZYOgZZBweHSxc3nz	MmjLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2NEO1NlMoRjJ2NESzOVI{RC:jPh?=
GBM	M37RTWFxd3C2b4Ppd{BCe3OjeR?=	M4LQ[FLPxE1?	M3;tZ\|Q5cA>?	NX7E[JRYTE2VTx?=	MYXpcoR2[2WmIHjp[4hmeiCuZY\lcJMhd2ZiYYDvdJRwe2m\|LDDhcoQh\GWlcnXhd4VlKGOnbHygeoli[mmuaYT5	M17jWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NUCwOFkzLz5{NEWwNFQ6OjxxYU6=
FaDu	MYLGeY5kfGmxbjDBd5NigQ>?	M4e2clUh\|ryP	M4W5SVI1KGh?	M1zhUGROW09?	M1K5dHJm\HWlZYOgc5h6\2WwIHPvcpN2dXC2aX;u	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDZ\|MUG0O{c,OjR4M{GxOFc9N2F-
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BT-20	MmrrS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NFrMbI0yKM7:TR?=	MmnYOUBl	MlfISG1UVw>?	NYLvbm9SUUN3MEyxJO69VQ>?	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDh5OUe5Okc,OjR6N{m3PVY9N2F-
MDA-MB-435	NHLnXVRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NVzK[INVOSEQvF2=	NHf5fIE2KGR?	M4\tW2ROW09?	NGHuNWlKSzVyPEGg{txO	M2nSO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OEe5O\|k3Lz5{NEi3PVc6PjxxYU6=
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A2780	NInkWnFHfW6ldHnvckBCe3OjeR?=		MYSxJIg>	M4H1VWROW09?	MWDJcohq[mm2aX;uJI9nKFCLM1utcYVlcWG2ZXSgRWtVKFOnckS3N{BxcG:\|cHjvdplt[XSrb36gbY4hWFSHTj3k[YZq[2mnboSgbJVu[W5iQUK3PFAh[2WubIOge4l1cCCHQ{WwJI9nKDBwMEe0JO69VQ>?	NFLZeG89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEmwNFI3Pid-MkS5NFAzPjZ:L3G+
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H596	NYOxcFJQTnWwY4Tpc44hSXO\|YYm=	NH23WHMyKM7:TR?=			M3vCW2lueGGrcoOgZ4VtdCCvaXfyZZRqd25?	M2P4TlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MEGzN\|E5Lz5{NkCxN\|MyQDxxYU6=
HCC2450	NXLEO4tUTnWwY4Tpc44hSXO\|YYm=	M2[3eFEh\|ryP			MVPJcZBicXK\|IHPlcIwhcW64YYPpc44>	MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjBzM{OxPEc,OjZyMUOzNVg9N2F-
HCT116	NGDKSlBCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NVjNdpdoPzJiaILz		NV7LfHV3SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDIR3QyOTZiY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JG1VXCCjc4PhfUwhUUN3MDC9JFAvPDhizszNMi=>	M{DDOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{[1PVA6Lz5{NUe2OVkxQTxxYU6=
MCF7	Mk[zRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		NY[zUWU4PzJiaILz		NIXOfGpCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIF3DSlch[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OCB;IEGg{txONg>?	M125[\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{[1PVA6Lz5{NUe2OVkxQTxxYU6=
U87MG	NH[4cGhCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NIDBO3c4OiCqcoO=		NHrEPHNCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIGW4O21IKGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTBiPTCxMlY1KM7:TT6=	NEHWZXk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe2OVkxQSd-MkW3OlU6ODl:L3G+
A549	NVHldGdkSW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		M4\tOVczKGi{cx?=		M4jn[GFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iQUW0PUBk\WyuczDh[pRmeiB5MjDodpMh[nliTWTUJIF{e2G7LDDJR\|UxKD1iMj6wO{DPxE1w	NHLlN2k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe2OVkxQSd-MkW3OlU6ODl:L3G+
HeLa	NV\mWml[SW62aYDyc4xq\mW{YYTpeoUh[XO\|YYm=		NHnJZ5U4OiCqcoO=		MnSzRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCKZVzhJINmdGy\|IHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVAhRSB2LkO0JO69VS5?	Mmn6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV5NkW5NFkoRjJ3N{[1PVA6RC:jPh?=
HCT116	NYP5XmZGTnWwY4Tpc44h[XO\|YYm=	M1fkNFExKHWP	MU[xJIhz		NVrD[2ZYUW6qaXLpeIlwdiCxZjDQTVNMN0GtdDDpckBpfW2jbjDIR3QyOTZiY3XscJMh[XO\|ZYPz[YQh[XNiQXv0JJBpd3OyaH;yfYxifGmxbjDheEAyOCC3TTDh[pRmeiBzIHjyJIJ6KFenc4Tldo4h[myxdITpcoch[W6jbInzbZM>	NGHWXWI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe2OVkxQSd-MkW3OlU6ODl:L3G+
A2058 melanoma	MkD2R4VtdCCleXPs[UBie3OjeR?=	MlLiOUB2VQ>?	NYLPNIVjOjRiaILz		Ml7lR4VtdCCleXPs[UBienKnc4SgbY4hcHWvYX6gRVIxPThibXXsZY5wdWFiY3XscJMh[XO\|ZYPz[YQh[XNiYXPjeY12dGG2aX;uJIF1KFO3YlexJJBp[XOnIHH0JFUhfU1iYX\0[ZIhOjRiaILzJIJ6KHC{b4Dp[Il2dSCrb3Tp[IUhe3SjaX7pcoch[mG\|ZXSgSmFEWyCjbnHsfZNqew>?	M3nxT\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6OEK5OVkzLz5{OEiyPVU6OjxxYU6=
A2058 melanoma	M3LESGNmdGxiY4njcIUh[XO\|YYm=	NUnvVmdqPSC3TR?=	MkLBNlQhcHK\|		MX3D[YxtKGO7Y3zlJIFzemW\|dDDpckBpfW2jbjDBNlA2QCCvZXzhco9u[SClZXzsd{Bie3Onc4Pl[EBieyCjY3P1cZVt[XSrb36gZZQhTzJxTTDwbIF{\SCjdDC1JJVOKGGodHXyJFI1KGi{czDifUBxem:yaXTpeY0hcW:maXTlJJN1[WmwaX7nJIJie2WmIF\BR3Mh[W6jbInzbZM>	M3fYNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ6OEK5OVkzLz5{OEiyPVU6OjxxYU6=
SKOV3	NVXZWZRES2WubDDjfYNt\SCjc4PhfS=>	MUGyJJVO	Mn7sNlQhcHK\|		NIXpOXJE\WyuIHP5Z4xmKGG{cnXzeEBqdiCqdX3hckBUU0:YMzDj[YxteyCjc4Pld5Nm\CCjczDhZ4N2dXWuYYTpc44h[XRiR{KvUUBxcGG\|ZTDheEAzKHWPIHHmeIVzKDJ2IHjyd{BjgSCycn;wbYRqfW1iaX;kbYRmKHO2YXnubY5oKGKjc3XkJGZCS1NiYX7hcJl{cXN?	NFPi[Xo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEiyPVU6Oid-Mki4Nlk2QTJ:L3G+
SKOV3	Mn;vR4VtdCCleXPs[UBie3OjeR?=	MYqyJJVO	NEXacZUzPCCqcoO=		MVjD[YxtKGO7Y3zlJIFzemW\|dDDpckBpfW2jbjDTT29XOyClZXzsd{Bie3Onc4Pl[EBieyCjY3P1cZVt[XSrb36gZZQhW3WkR{GgdIhie2ViYYSgNkB2VSCjZoTldkAzPCCqcoOgZpkheHKxcHnkbZVuKGmxZHnk[UB{fGGrbnnu[{Bj[XOnZDDGRWNUKGGwYXz5d4l{	NEXmZVE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEiyPVU6Oid-Mki4Nlk2QTJ:L3G+
MDA-MB-231	NUXxeXNQS3m2b4TvfIlkcXS7IHHzd4F6		Mn;ZO\|IhcHK\|		MkDrR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUWRCNU2ELUKzNUBk\WyuczDh[pRmeiB5MjDodpMh[nliTWTUJIF{e2G7LDDJR\|UxKD1iMT64PEDPxE1w	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTFyN{SyPUc,OjlzMEe0Nlk9N2F-
PC3	M1zMR2N6fG:2b4jpZ4l1gSCjc4PhfS=>		NEi1cZM4OiCqcoO=		M1TCTmN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJHBEOyClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG\|c3H5MEBKSzVyIE2gOU4{PCEQvF2u	NEnHRXY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUGwO\|QzQSd-MkmxNFc1Ojl:L3G+
T47D	M4jnOWN6fG:2b4jpZ4l1gSCjc4PhfS=>		MVi3NkBpenN?		MnrRR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gWFQ4TCClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG\|c3H5MEBKSzVyIE2gOk46OiEQvF2u	NXnheppRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmxNFc1OjlpPkK5NVA4PDJ7PD;hQi=>
MCF7	NVy2dpRxS3m2b4TvfIlkcXS7IHHzd4F6		M4\iVVczKGi{cx?=		M4m0fGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJG1ETjdiY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JG1VXCCjc4PhfUwhUUN3MDC9JFEyNjB3IN88UU4>	NFn5PGg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUGwO\|QzQSd-MkmxNFc1Ojl:L3G+
TC32	MXzxTHRUKGG\|c3H5				M2KyZ5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCWQ{OyJINmdGy\|	NHL2T5Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
A673	M1vOdZFJXFNiYYPzZZk>				MnvWdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEF4N{OgZ4VtdHN?	M1fwelxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
DAOY	Mn;LdWhVWyCjc4PhfS=>				MVnxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhTEGRWTDj[Yxtew>?	MX[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Saos-2	NXrlUYZneUiWUzDhd5NigQ>?				NFzQS2xyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU3Hvd{0zKGOnbHzz	NHnZWpM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
BT-37	Mn[zdWhVWyCjc4PhfS=>				MnTwdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUO3JINmdGy\|	M{n3OVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
RD	NGXhXJZyUFSVIHHzd4F6				NXW1NYtyeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLEJINmdGy\|	NE\tdoM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SK-N-SH	MVHxTHRUKGG\|c3H5				M2HtTpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMXNJKGOnbHzz	M{HWeFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
BT-12	MljSdWhVWyCjc4PhfS=>				MkXsdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUGyJINmdGy\|	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
MG 63 (6-TG R)	NVLVfGZweUiWUzDhd5NigQ>?				NHHiWYFyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTVegOlMhMDZvVFegVkkh[2WubIO=	NYTReYZGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB1643	M4jVbJFJXFNiYYPzZZk>				MkjJdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6EMU[0N{Bk\Wyucx?=	NEfh[Wo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
OHS-50	NG[xPFRyUFSVIHHzd4F6				MWHxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhV0iVLUWwJINmdGy\|	MnfsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-SH	MXnxTHRUKGG\|c3H5				M1GzXZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHNMNU5vU1igZ4VtdHN?	MmLWQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Rh41	M{G4c5FJXFNiYYPzZZk>				NUjCTGxzeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLoOFEh[2WubIO=	M134UlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
A673	NXrZd5l{eUiWUzDhd5NigQ>?				MlLydWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgRVY4OyClZXzsd{k>	M{nCd\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Rh30	NUXRPIVxeUiWUzDhd5NigQ>?				MVPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmh\|MDDj[Yxtew>?	NVHqS5lXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
MG 63 (6-TG R)	MUnxTHRUKGG\|c3H5				MlXOdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgUWchPjNiKE[tWGchWiliY3XscJM>	Mn3vQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Rh30	NIrMNpByUFSVIHHzd4F6				NXLHcJB1eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhWmh\|MDDj[Yxtew>?	M1rDUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
U-2 OS	NVLmdo51eUiWUzDhd5NigQ>?				MlOzdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgWU0zKE:VIHPlcIx{	M2G2fVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
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insect	MUDGeY5kfGmxbjDhd5NigQ>?				M{\LR2lvcGmkaYTpc44hd2ZicnXjc41jcW6jboSgbJVu[W5iSHnzMZRi\2enZDDwPFVidHCqYT;wNVEx[WyyaHGgSVU1PUtibYX0ZY51KGW6cILld5Nm\CCrbjDpcpNm[3RiY3XscJMtKEmFNUCgQUAxNjBzMTFOwG0v	NGfQWHc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MECzOFYxPyd-M{CwN\|Q3ODd:L3G+
insect	NHLBPHhHfW6ldHnvckBie3OjeR?=				MoO1TY5pcWKrdHnvckBw\iC{ZXPvcYJqdmGwdDDoeY1idiCKaYOteIFo\2WmIIC4OYFteGijL4CxNVBidHCqYTDFOVQzUyCvdYThcpQh\XiycnXzd4VlKGmwIHnud4VkfCClZXzsd{whUUN3MDC9JFAvODJ7IN88UU4>	MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODB\|NE[wO{c,OzByM{S2NFc9N2F-
Sf21	NXvkU3JDTnWwY4Tpc44h[XO\|YYm=		MmjHNUBpeg>?		NWrOU2w2UW6qaXLpeIlwdiCxZjDy[YNwdWKrbnHueEBpfW2jbjDmeYxtNWynbnf0bEBPNXSncn3pcoFtKEirc{[teIFo\2WmIICxNVBl\Wy2YT;y[YNwdWKrbnHueEBpfW2jbjDmeYxtKGynbnf0bEBxQDWjbIDoZUBmgHC{ZYPz[YQhcW5iYnHjeYxwfmm{dYOgbY5n\WO2ZXSgV4YzOSCrboPlZ5Qh[2WubIOgeZNqdmdiUFnQNkBieyC\|dXLzeJJifGVibXXhd5Vz\WRiYX\0[ZIhOSCqcjDifUBCdGW6YU[zN{BVemGlZYKtZoF{\WRiZnz1c5Jme2OnbnPlJJBwdGG{LDDJR\|UxKD1iMD6xNlUh\|ryPLh?=	MkfkQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzByM{S2NFcoRjNyMEO0OlA4RC:jPh?=
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Sf21	Mlq0SpVv[3Srb36gZZN{[Xl?		MVixJIhz		MnH6TY5pcWKrdHnvckBw\iC{ZXPvcYJqdmGwdDDoeY1idiCodXzsMYxmdme2aDDOMZRmem2rbnHsJGhqezZvdHHn[4VlKHBzMUDi[ZRiN3KnY3;tZolv[W62IHj1cYFvKG[3bHygcIVv\3SqIIC4OYFteGijIHX4dJJme3OnZDDpckBj[WO3bH;2bZJ2eyCrbn\lZ5Rm\CCVZkKxJIlve2WldDDj[YxteyC3c3nu[{BRUVB{IHHzJJN2[nO2cnH0[UBu\WG\|dYLl[EBi\nSncjCxJIhzKGK7IFHs[ZhiPjN\|IGTyZYNmei2kYYPl[EBndHWxcnXzZ4Vv[2VicH;sZZJqNCCLQ{WwJF0hOC5{M{Sg{txONg>?	NXy4WpFXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CwN\|Q3ODdpPkOwNFM1PjB5PD;hQi=>
T47D	M4[5WWFvfGmycn;sbYZmemG2aY\lJIF{e2G7		M{DWSlczKGi{cx?=		Mn3uRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCWNEfEJINmdGy\|IHjhdoJwemmwZzDQTVNMS0FiSEGwOFdTKG23dHHueEBi\nSncjC3NkBpenNiYomgUXRVKGG\|c3H5MEBKSzVyIE2gNE4zQDZizszNMi=>	M4W1SFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMEO0OlA4Lz5\|MECzOFYxPzxxYU6=
PC3	NFq0PFRHfW6ldHnvckBie3OjeR?=		NGLqeFczKGi{cx?=		MX;Jcohq[mm2aX;uJI9nKFCLM1ugbY4hcHWvYX6gVGM{KGOnbHzzJIF{e2W\|c3XkJIF{KHKnZIXjeIlwdiCrbjDBT3QheGixc4Doc5J6dGG2aX;uJIF1KFOnckS3N{Bu\WG\|dYLl[EBi\nSncjCyJIhzeyCkeTDmcJVwemW\|Y3XuZ4Uh[XO\|YYmsJGlEPTBiPTCwMlM3PSEQvF2u	MoLlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzByM{S2NFcoRjNyMEO0OlA4RC:jPh?=
HT-29	MmTOR4VtdCCleXPs[UBie3OjeR?=	MkLONE4yOTFidH:gN{B2VQ>?	NWrqVpFWOjRiaILz		NH:wbVFE\WyuIHP5Z4xmKGG{cnXzeEBqdiCqdX3hckBJXC1{OTDj[YxteyCjc4Pld5Nm\CCjczDhZ4N2dXWuYYTpc44h[XRiR{KvUUBxcGG\|ZTDheEAxNjFzMTD0c{A{KHWPIHHmeIVzKDJ2IHjyd{BjgSCycn;wbYRqfW1iaX;kbYRmKHO2YXnubY5oKGKjc3XkJIZtd3diY4n0c41mfHK7	NYnNUWpURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CwN\|Q3ODdpPkOwNFM1PjB5PD;hQi=>
A2058	MnHaSpVv[3Srb36gZZN{[Xl?		NGmzSWsyKGi{		M3fhXGlvcGmkaYTpc44hd2ZiVF;SR\|IhcW5iaIXtZY4hSTJyNUigZ4VtdHNiYYPz[ZN{\WRiYYOg[IVkemWjc3WgbY4hWEuEL1HreEBxcG:\|cHjvdplt[XSrb36gZZQhW2W{NEezJIFnfGW{IEGgbJIh[nliV3XzeIVzdiCkbH;0JIFv[Wy7c3nzMEBKSzVyIE2gNE41OTZizszNMi=>	Mmf6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB\|NUmwNFMoRjNyM{W5NFA{RC:jPh?=
A2058	NWnUZYlETnWwY4Tpc44h[XO\|YYm=		Ml\1NUBpeg>?		M3zLTmlvcGmkaYTpc44hd2ZiVF;SR\|EhcW5iaIXtZY4hSTJyNUigZ4VtdHNiYYPz[ZN{\WRiYYOg[IVkemWjc3WgbY4hWzZicHjvd5Bpd3K7bHH0bY9vKGG2IGPldlI{PS9{M{[gZYZ1\XJiMTDodkBjgSCZZYP0[ZJvKGKub4SgZY5idHm\|aYOsJGlEPTBiPTCwMlU2OyEQvF2u	NIHuWnM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEO1PVAxOyd-M{CzOVkxODN:L3G+

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	p-AKT (T308) / p-AKT (S473) / AKT; PubMed: 27283525 J Neurooncol Left western blots showing levels of pAkt (T308), pAkt (S473) and total Akt in U87 cells exposed to buparlisib for 72 h. Right densitometric assessment of western blots, showing relative changes in phosphorylation. p-FOXO3a (S253) / FOXO3a; PubMed: 28036259 Oncotarget Cells were treated with 0.5 μM BKM120 for 24 h and cell lysates were immunoblotted with the indicated antibodies. Actin was used as the loading control. Nuclear NF-κB p65 / NF-κB p65; PubMed: 26673665 Cell Death Dis Western blots show BKM120 downregulating pAKT, nuclear NF-κB p65 and total NF-κB p65 in MDR and their parental cells. β-actin was used as a loading control for pAKT, AKT and total NF-κB p65. Lamin B was used as a loading control for nuclear NF-κB p65. p-ERK / ERK / LC3; PubMed: 27572309 Oncotarget The indicated cell lines were exposed to different concentrations of BKM120 as indicated for 8 h A. or with 2 μM BKM120 for the indicated times B. The cells were then harvested for preparation of whole-cell protein lysates and subsequent Western blot analysis to detect the given proteins. p-STAT3 / STAT3 / p-ERK / ERK / p-S6; PubMed: 29928341 Oncol Lett Western blot analysis of H460 and H2126 cell lysates using specific antibodies to phosphorylated or total proteins of STAT3, ERK1/2, AKT, S6 or GAPDH (loading control). The cells were treated with increasing concentrations of BKM120 for 24 h. p-MET / MET; PubMed: 29928341 Oncol Lett The expression of phosphorylated or total forms of MET protein was analyzed by western blotting.	27283525 28036259 26673665 27572309 29928341
Immunofluorescence	FOXO3a; PubMed: 28036259 Oncotarget Cells were cultured on coverslips to approximately 60% confluency and then treated with 1 μM BKM120 for an additional 24 h. Immunofluorescence staining was performed using an anti-FOXO3a antibody and the nuclei were stained with DAPI. Scale bar, 20 μm.	28036259
Growth inhibition assay	Cell viability; PubMed: 26673665 Cell Death Dis Dose-response curves were used to calculate the IC50 of BKM120 for MCs of MCF-7/A02 cells (upper) and CALDOX cells (lower).	26673665

In vivo

BKM120 completely inhibits pAktser473 in A2780 xenograft tumors at doses of 30, 60, or 100 mg/kg, respectively. BKM120 also shows antitumor activity against U87MG glioma model at doses of 30 and 60 mg/kg. ^[1] BKM120 treatment results in significantly reduced tumor volume and level of circulating human kappa chain at 5 μM/kg/day−1in ARP1 SCID mouse model, with prolonged survival. ^[2]

Protocol

Kinase Assay:^[1]	- Collapse PI3K biochemical assay (ATP depletion assay): BKM120 is dissolved in DMSO and directly distributed into a black 384-well plate at 1.25 µL per well. To start the reaction, 25 µL of 10 nM PI3 kinase and 5 µg/mL 1-α-phosphatidylinositol (PI) in assay buffer (10 mM Tris pH 7.5, 5 mM MgCl₂, 20 mM NaCl, 1 mM DTT and 0.05% CHAPS) are added into each well followed by 25 µL of 2 µM ATP in assay buffer. The reaction is performed until approx 50% of the ATP is depleted and then stopped by the addition of 25 µL of KinaseGlo solution. The stopped reaction is incubated for 5 minutes and the remaining ATP is then detected via luminescence.
Cell Research:^[1]	- Collapse Cell lines: A2780 cells. Concentrations: 0-6.6 μM Incubation Time: 3 days. Method: A2780 cells are cultured in DMEM supplemented with 10% FBS, L-glutamine, sodium pyruvate, and antibiotics. Cells are plated in the same medium at a density of 10³ cells per well, 100 μL per well into black-walled-clear-bottom plates and incubated for 3-5 hours. BKM120 supplied in DMSO (20 mM) is diluted. The diluted BKM120 solution (2 μL), is then added to cell medium (500 μL) cell medium (concentration from 0-6.6 μM). Equal volumes of this solution (100 μL) are added to the cells in 96 well plates and incubated at 37 °C for 3 days and developed using Cell Titer Glo. Inhibition of cell proliferation is determined by luminescence read using Trilux. (Only for Reference)
Animal Research:^[1]	- Collapse Animal Models: U87MG and A2780 xenografts are established in female nu/nu mice. Dosages: ~60 mg/kg. Administration: Dosed orally daily (q.d.). (Only for Reference)

References

[4] Koul D, et al. Clin Cancer Res, 2012, 18(1), 184-195.

- Collapse

Solubility (25°C)

In vitro	DMSO	82 mg/mL (199.8 mM)
	Ethanol	2 mg/mL (4.87 mM)
	Water	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 5% DMSO+30% PEG 300+ddH2O For best results, use promptly after mixing.	15mg/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 Buparlisib (BKM120) SDF

Molecular Weight	410.39
Formula	C₁₈H₂₁F₃N₆O₂
CAS No.	944396-07-0
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	NVP-BKM120
Smiles	C1COCCN1C2=NC(=NC(=C2)C3=CN=C(C=C3C(F)(F)F)N)N4CCOCC4

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Working concentration： mg/ml；

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

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

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

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04338399	Not yet recruiting	Drug: Buparlisib & Paclitaxel	Head and Neck Cancer	Adlai Nortye Biopharma Co. Ltd.	July 31 2020	Phase 3
NCT02614508	Terminated	Drug: Buparlisib\|Drug: Ibrutinib\|Biological: Ofatumumab	Recurrent Chronic Lymphocytic Leukemia\|Recurrent Small Lymphocytic Lymphoma\|Refractory Chronic Lymphocytic Leukemia\|Refractory Small Lymphocytic Lymphoma	Emory University\|Novartis	January 2016	Phase 1
NCT01613677	Withdrawn	Drug: BKM120	Treatment for Metastatic or Locally Advanced Cervical Cancer	Novartis Pharmaceuticals\|Novartis	November 2015	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

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PI3K Signaling Pathway Map

PI3K Inhibitors with Unique Features

Selective PI3K Inhibitors

CAL-101 (Idelalisib, GS-1101) : p110δ-selective, IC50=2.5 nM.
Selective PI3K Inhibitors

TGX-221 : p110β-specific, IC50=5 nM.
Most Potent PI3K Inhibitor

BEZ235 (NVP-BEZ235, Dactolisib) : p110α/γ/δ/β, IC50=4 nM/5 nM/7 nM/75 nM.
FDA-approved PI3K Inhibitor

CAL-101 (Idelalisib, GS-1101) : Approved by FDA for Relapsed Chronic Lymphocytic Leukemia, Follicular Lymphoma and Small Lymphocytic Lymphoma.
Newest PI3K Inhibitor

VS-5584 (SB2343) ^New : Potent and selective dual PI3K/mTOR inhibitor for mTOR, PI3Kα/β/δ/γ with IC50 of 3.4 nM and 2.6-21 nM, respectively.

Related PI3K Products

Taselisib (GDC 0032) ^New

Taselisib (GDC 0032, RG7604) is a potent, next-generation β isoform-sparing PI3K inhibitor targeting PI3Kα/δ/γ with K_i of 0.29 nM/0.12 nM/0.97nM, >10 fold selective over PI3Kβ.

Features:A beta isoform-sparing PI3K inhibitor.
Pilaralisib (XL147) ^New

Pilaralisib (XL147) is a selective and reversible class I PI3K inhibitor for PI3Kα/δ/γ with IC50 of 39 nM/36 nM/23 nM in cell-free assays, less potent to PI3Kβ. Phase 1/2.
GNE-317 ^New

GNE-317 is a potent, brain-penetrant PI3K inhibitor.
LY294002

LY294002 (SF 1101, NSC 697286) is the first synthetic molecule known to inhibit PI3Kα/δ/β with IC50 of 0.5 μM/0.57 μM/0.97 μM, respectively; more stable in solution than Wortmannin, and also blocks autophagosome formation. It not only binds to class I PI3Ks and other PI3K-related kinases, but also to novel targets seemingly unrelated to the PI3K family. LY294002 also inhibits CK2 with IC50 of 98 nM. LY294002 is a non-specific DNA-PKcs inhibitor and activates autophagy and apoptosis.
3-Methyladenine (3-MA)

3-Methyladenine (3-MA, NSC 66389) is a selective PI3K inhibitor for Vps34 and PI3Kγ with IC50 of 25 μM and 60 μM in HeLa cells; blocks class I PI3K consistently, whereas suppression of class III PI3K is transient, and also blocks autophagosome formation. 3-Methyladenine (3-MA) is successfully used to suppress mitophagy. Solutions of 3-MA are best fresh-prepared by heating.
Idelalisib (CAL-101, GS-1101)

Idelalisib (CAL-101, GS-1101) is a selective p110δ inhibitor with IC50 of 2.5 nM in cell-free assays; shown to have 40- to 300-fold greater selectivity for p110δ than p110α/β/γ, and 400- to 4000-fold more selectivity to p110δ than C2β, hVPS34, DNA-PK and mTOR. Idelalisib also stimulates autophagy.
Wortmannin

Wortmannin (KY 12420, SL-2052) is the first described PI3K inhibitor with IC50 of 3 nM in a cell-free assay, with little selectivity within the PI3K family. Wortmannin blocks autophagosome formation and potently inhibits DNA-PK/ATM with IC50 of 16 nM and 150 nM in cell-free assays. Wortmannin also inhibits PLK1 activity.
Dactolisib (BEZ235)

Dactolisib (BEZ235, NVP-BEZ235) is a dual ATP-competitive PI3K and mTOR inhibitor for p110α/γ/δ/β and mTOR(p70S6K) with IC50 of 4 nM /5 nM /7 nM /75 nM /6 nM in cell-free assays, respectively. Inhibits ATR with IC50 of 21 nM in 3T3^TopBP1-ER cell. Dactolisib induces autophagy and suppresses HIV-1 replication. Phase 2.
Pictilisib (GDC-0941)

Pictilisib (GDC-0941, RG7321) is a potent inhibitor of PI3Kα/δ with IC50 of 3 nM in cell-free assays, with modest selectivity against p110β (11-fold) and p110γ (25-fold). Pictilisib (GDC-0941) induces autophagy and apoptosis. Phase 2.
Alpelisib (BYL719)

Alpelisib (BYL719) is a potent and selective PI3Kα inhibitor with IC50 of 5 nM in a cell-free assay, and minimal effect on PI3Kβ/γ/δ. Phase 2.

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Buparlisib (BKM120)