Buparlisib (BKM120)

Name: Buparlisib (BKM120)
Brand: Selleck Chemicals
SKU: S2247
Rating: 5 (212 reviews)

For research use only.

Catalog No.S2247 Synonyms: NVP-BKM120

212 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 212 publications

Cancer Cell, 2021, S1535-6108(21)00284-1

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Cell, 2020, 25;181(7):1596-1611.e27.

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Cell, 2020, S0092-8674(20)31394-5

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Cancer Cell, 2020, 37(2):183-199

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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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Cancer Discov, 2013, 4(2):232-45

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Cancer Discov, 2013, 4(2):186-99

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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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Mol Cell, 2021, S1097-2765(21)00232-X

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Nat Commun, 2021, 12(1):5053

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Nat Commun, 2021, 12(1):1920

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Nat Commun, 2021, 12(1):3140

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

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Cancer Res, 2021, canres.CAN-21-0164-A.2021

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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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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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Am J Cancer Res, 2020, 10(12):4488-4497

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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):2910

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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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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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Cell Rep, 2018, 24(2):463-478

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Elife, 2018, 7e33718

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

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Int J Cancer, 2018, 142(9):1926-1937

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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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Mol Cancer Ther, 2018, 17(7):1526-1539

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Sci Rep, 2018, 8(1):10784

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

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Oncol Rep, 2018, 40(1):479-487

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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 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(32):52474-52487

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

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Oncotarget, 2017, 8(13):21806-21817

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Oncotarget, 2017,

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Oncotarget, 2017, 8(44):76935-76948

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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,

PubMed: 27292631 ( click the link to review the publication )

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

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

PubMed: 27604488 ( click the link to review the publication )

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(29):45414-45428

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

PubMed: 27572309 ( click the link to review the publication )

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

PubMed: 26846842 ( click the link to review the publication )

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

PubMed: 27579615 ( click the link to review the publication )

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

PubMed: 26272820 ( click the link to review the publication )

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

PubMed: 26124089 ( click the link to review the publication )

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

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

Oncogene, 2015, 10.1038/onc.2015.173

PubMed: 25982275 ( click the link to review the publication )
Glia, 2015, 63(10):1850-9

PubMed: 25944104 ( click the link to review the publication )

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

PubMed: 26293922 ( click the link to review the publication )

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

PubMed: 25933683 ( click the link to review the publication )

Biomed Pharmacother, 2015, 75:40-50

PubMed: 26463630 ( click the link to review the publication )

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

PubMed: 26397139 ( click the link to review the publication )

Crit Rev Oncol Hematol, 2015,

PubMed: 26253360 ( click the link to review the publication )

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

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

PubMed: 25250573 ( click the link to review the publication )

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

PubMed: 24451154 ( click the link to review the publication )
Breast Cancer Res, 2014, 16(4):406

PubMed: 25103565 ( click the link to review the publication )

Cell Death Dis, 2014, 5:e1134

PubMed: 24651437 ( click the link to review the publication )

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

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

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

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

PubMed: 23311350 ( click the link to review the publication )

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	M1;UNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		NUjuN2pEPzKq		MYXJR\|UxRTFvMt88US=>	NFn6SZc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkC2OVA5OCd-MkKwOlUxQDB:L3G+
U87	M12xSWFxd3C2b4Ppd{BCe3OjeR?=	MmSyNu69VQ>?	M4fsclczcA>?		M3rXNYlv\HWlZYOgZ4VtdCCjcH;weI9{cXNiYX7kJINt\WG4ZXSgVGFTWCCjbnSgZ4F{eGG\|ZT2z	M{DCbVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{ME[1NFgxLz5{MkC2OVA5ODxxYU6=
SNU-601	Mmr5S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		MmHXO\|Jp	MoPNSG1UVw>?	NWK4e3Q4UUN3ME2wMlgyPsLzMD6wOlPPxE1?	NILNWVE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkG1PVgyPCd-MkKxOVk5OTR:L3G+
SNU-1	M3n0fmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		NYLtW4NuPzKq	M2jEcWROW09?	NGf2VYRKSzVyPUGuNFgzyrFyLkCyPO69VQ>?	NX7BN5VFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKxOVk5OTRpPkKyNVU6QDF2PD;hQi=>
SNU-668	NGHLXnpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		MW[3Nog>	NUnJXVd4TE2VTx?=	MXzJR\|UxRTFwNUe5xtExNjB5NN88US=>	NYXzeohZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKxOVk5OTRpPkKyNVU6QDF2PD;hQi=>
AGS	NWPsPJlNT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		NV73PJcyPzKq	MnnqSG1UVw>?	NXn5SXF3UUN3ME2xMlcyPMLzMD6xNVfPxE1?	MnT3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJzNUm4NVQoRjJ{MUW5PFE1RC:jPh?=
SNU-216	NV7IbIlwT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		NWG4TllpPzKq	NI\4fZhFVVOR	NITVeYZKSzVyPUKuOlkzyrFyLkC4Nu69VQ>?	M3uzU\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MUW5PFE1Lz5{MkG1PVgyPDxxYU6=
SNU-5	M1Lqemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		NGnYb4c4Omh?	M3PyTWROW09?	M{fkO2lEPTB;MT6zOVHDuTBwMEmx{txO	M{fNXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MUW5PFE1Lz5{MkG1PVgyPDxxYU6=
SNU-638	NYCwR4FxT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		NHywOXE4Omh?	MlTwSG1UVw>?	MoHQTWM2OD1{LkK4NuKyOC5yNUROwG0>	NX:zSnp7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKxOVk5OTRpPkKyNVU6QDF2PD;hQi=>
SNU-16	MkXyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		NWnoT4FWPzKq	NXmxeoU2TE2VTx?=	NX7kcGQ4UUN3ME2xMlU4O8LzMD6wNFHPxE1?	NXr1OGNJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKxOVk5OTRpPkKyNVU6QDF2PD;hQi=>
SNU-484	MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		NF;1dWI4Omh?	MV3EUXNQ	MYrJR\|UxRTFwN{K4xtExNjB2Nd88US=>	NW[4XJdmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKxOVk5OTRpPkKyNVU6QDF2PD;hQi=>
SNU-620	MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		Mly2O\|Jp	NGnlV3NFVVOR	NH22emVKSzVyPUKuPVM6yrFyLkCwNe69VQ>?	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjF3OUixOEc,OjJzNUm4NVQ9N2F-
SNU-719	M{\mO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7		MVm3Nog>	NEfo[IpFVVOR	MneyTWM2OD1\|LkCzO:KyOC5yM{NOwG0>	M3vjVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MUW5PFE1Lz5{MkG1PVgyPDxxYU6=
MM cell lines	NIPwWmFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MYixNO69VQ>?	MWSyOIg>	NX32PIVHTE2VTx?=	M1LKfWlEPTBidnHybYV{KGGvb37nJIRq\m[ncnXueEBk\WyuIHzpcoV{KGmwIITpcYUh[W6mIHTvd4Uh\GWyZX7k[Y5k\Q>?	NX3xTXRRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKyNFc1QDVpPkKyNlA4PDh3PD;hQi=>
ARP-1	NUf2eI9nSXCxcITvd4l{KEG\|c3H5	M{[4bFEx\|ryP	Mom2NlRp	M{DIT2ROW09?	MX3pcoR2[2W\|IF3NJINmdGxiYYDvdJRwe2m\|IITodo92\2hiY3HzdIF{\SCjY4TpeoF1cW:w	NUPYUm9iRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKyNFc1QDVpPkKyNlA4PDh3PD;hQi=>
colon cancer cell lines	NHS4SmpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NUnj[XhIOC1zMN88US=>	NVriZ4Z5PzKq	MW\EUXNQ	M1yyPWlEPTB;Md88US=>	MkTOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ3NEO4OVcoRjJ{NUSzPFU4RC:jPh?=
gastric cancer cell lines	M2rHTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MljvNE0yOM7:TR?=	NXq5W2lRPzKq	NEjvUWxFVVOR	M33OR2lEPTB;Mj21{txO	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjV2M{i1O{c,OjJ3NEO4OVc9N2F-
HCT-116/HT-29/MKN-45	MXvBdI9xfG:\|aYOgRZN{[Xl?	NHzEeo4z\|ryP	NIq5Vo41QGh?		NUTac2lRe2irZoSgbY4hTzJicHjhd4U>	MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjV2M{i1O{c,OjJ3NEO4OVc9N2F-
HT-29 and HCT-116	M2G3dGNie3Cjc3WgZZN{[Xl?	MofUOe69VQ>?	NH;3co0zPGh?		NW\Sfm5QcW6mdXPld{Bk[XOyYYPlJIFkfGm4aYT5	NY\FRYdVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK1OFM5PTdpPkKyOVQ{QDV5PD;hQi=>
PIK3CA-mutant MCF7	NXnrVmlZT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MlHCS2k2OD1zNkFCtVkydk4xvJzMSFUxRTl6MNMxNlc{dk1?	Mn22O\|Jp		M13vc2dKPTB;MU[wxtE6OW6P78{MUGQ2OD17OEFCtVI4O26P	NGjEemE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{Mk[1N\|k3Pyd-MkK2OVM6Pjd:L3G+
PIK3CA-mutant MCF7	NUHFWHNuU2mwYYPlJGF{e2G7	NYDqUJdiUUN3ME2xNVTDuTOwTR?=	MknrO\|Jp		NGDNXI5KSzVyPUGxOOKyO26PIHnuJJJm\HWlaX7nJGFsfCCyaH;zdIhwenmuYYTpc44hdGW4ZXzz	NIT5XWY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{Mk[1N\|k3Pyd-MkK2OVM6Pjd:L3G+
MCF7-myr-Akt	MlLOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MXzHTVUxRTJ7OdMxOlhvVe,:jFzEOVDwxJ5zMDywNFBvVQ>?	M1Ty[\|czcA>?		NGr1OYJIUTVyPUK5PeKyPjiwTf-8kGxFPTExvK6xNEwxODCwTR?=	NXewbFh7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK2OVM6PjdpPkKyOlU{QTZ5PD;hQi=>
Y1 cell line	NHPs[GJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MVewMlHPxE1xMd88US=>	Mo[3NlRp	NUC2WHVYTE2VTx?=	M33IOIlvcGmkaYTzJFYx97zHIHPlcIwhfmmjYnnsbZR6KGmwIF35Z{1U[3S{LYTyZY5{\mWldHXkJINmdGy\|	M1vKVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{NkmyPVA1Lz5{Mk[5NlkxPDxxYU6=
human NSCLC	MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M37vPVAvPS1{zszN	MWK3Nog>		M4Wxd2lEPTB;Md88US=>	M{P0elxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{N{ixN\|k{Lz5{Mke4NVM6OzxxYU6=
human NSCLC	M{nuRmtqdmG\|ZTDBd5NigQ>?	MoT3Ne69VQ>?	MVmyOIg>		M1G4WIlvcGmkaYTzJJRp\SCDa4SvcXRQWiC\|aXfuZYxqdmdicHH0bJdigSCjdDCzbEBi\nSncjD0doVifG2nboS=	NHLtZ\|A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{Mke4NVM6Oyd-MkK3PFE{QTN:L3G+
JVM2	NXjUTItmS3m2b4TvfIlkcXS7IHHzd4F6	M{WxNlAvOi1{MN88US=>	MmDlO\|Jp	MVXEUXNQ	MofzTWM2OD1yLkpOwG0>	Mne2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN{M{i2N\|koRjJ\|MkO4OlM6RC:jPh?=
EHEB	M4DwZ2N6fG:2b4jpZ4l1gSCjc4PhfS=>	MYSwMlIuOjEQvF2=	MmqxO\|Jp	NHfZNGJFVVOR	M1q1UmlEPTB;MD63{txO	NHiwfJY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{KzPFY{QSd-MkOyN\|g3Ozl:L3G+
MEC2	Ml7yR5l1d3SxeHnjbZR6KGG\|c3H5	NIrIUFUxNjJvMkFOwG0>	NGT2TlU4Omh?	NX6wNWZ4TE2VTx?=	NXPGRYdMUUN3ME2wMlfPxE1?	M1jTdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|MkO4OlM6Lz5{M{KzPFY{QTxxYU6=
primary B-CLL lymphocytes	MlPVRZBweHSxc3nzJGF{e2G7	NGrFe3lKSzVyIH\vdkBm[WOqIIDybY1ienliY3XscEBtcW6n	MnvJNlRp	MmfBSG1UVw>?	MUDJR\|Ux97zeM988UUBnd3JiYXzsJJBifGmnboTz	MkXyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN{M{i2N\|koRjJ\|MkO4OlM6RC:jPh?=
primary B-CLL lymphocytes	NWjtR4VWU2mwYYPlJGF{e2G7	NE\sSndKSzVyIH\vdkBm[WOqIIDybY1ienliY3XscEBtcW6n	M2PvVlI1cA>?		MXfpcohq[mm2czDwO\|BUPktiJjC0SU1DWDFiZYjwdoV{e2mxbh?=	MlXlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN{M{i2N\|koRjJ\|MkO4OlM6RC:jPh?=
SK-HEP1	NFvIe45Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MXuxMVIx\|ryP	MV63Nog>	NFOz[5dFVVOR	MXvJR\|Ux97zeMd88US=>	Mm\qQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN2N{mxN\|YoRjJ\|NEe5NVM3RC:jPh?=
786-0	MlrUS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NXvuV2c6OS1{MN88US=>	NX64V5ZjPzKq	MmLXSG1UVw>?	M4q5[mlEPTExvKyx{txO	NEC1foc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{S3PVE{Pid-MkO0O\|kyOzZ:L3G+
human HCC cell lines	MVHD[YxtKH[rYXLpcIl1gSCjc4PhfS=>	NX\OZXFzOC5yMEWtNe69VQ>?	M1jwSFQ5cA>?		NUPPUoMzUUN3ME2x{txO	M1LLV\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NEi5PVk6Lz5{M{S4PVk6QTxxYU6=
Huh7	MVnLbY5ie2ViQYPzZZk>	M1;wcFHPxE1?	MVO0PIg>		M3uy[ZNq\26r77{BZ4FvfGy7IILl[JVk\XNicHjvd5Bpd3K7bHH0bY9vKG:oIFHreC=>	NVrpdJk3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO0PFk6QTlpPkKzOFg6QTl7PD;hQi=>
human NSCLC cell lines	NIPYPVZCeG:ydH;zbZMhSXO\|YYm=	MlmzNE4yOjVvNN88US=>	MXWyOIg>	Ml3oSG1UVw>?	NX;J[I16UUN3MIOgdoFv\2W\|IH\yc40hOC52LUNOwG0>	NETrUmc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{W2NlQ4Oid-MkO1OlI1PzJ:L3G+
Primary CLL cells	NFHyNlRCeG:ydH;zbZMhSXO\|YYm=	M{P0VVEuOTEQvF2=	MW[0PIg>		NV3Mc3ppcW6mdXPld{BieG:ydH;zbZMhcW5iQ1zMJINmdGy\|IHnu[IVx\W6mZX70JI9nKHC{b3fuc5N1cWNibXHyb4Vzew>?	Ml\qQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN6NUC4NFcoRjJ\|OEWwPFA4RC:jPh?=
Primary CLL cells	NFnQPXBMcW6jc3WgRZN{[Xl?	NHfI[Wwz\|ryP	NU\1TpY4OzCvaX6=		MlvW[IVkemWjc3XkJHBKO0tiYXP0bZZqfHl?	MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzh3MEiwO{c,OjN6NUC4NFc9N2F-
Primary CLL cells	MmW5R5l1d3SxeHnjJGF{e2G7	Ml;qNu69VQ>?	MojCNlRp		NV:4WWlucW6mdXPld{Bk\WyuIHP5eI91d3irY3n0fS=>	MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzh3MEiwO{c,OjN6NUC4NFc9N2F-
LC-1/SQSF	M{G0[mZ2dmO2aX;uJGF{e2G7	NHP5R3A{\|ryP	MmHpNlRp	NWK1ZmYxTE2VTx?=	M1vBR4Rm[3KnYYPlJG5TTjJicILveIVqdiCuZY\lcC=>	NHK5XWo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{m4NFA6Oyd-MkO5PFAxQTN:L3G+
BCR-ABL	MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MnK3NE4zPS1zMN88US=>	NVrzU45EPGR?		MmjOd4lodmmoaXPhcpRtgSCrbnjpZol1KGOnbHygdJJwdGmoZYLheIlwdg>?	MnTNQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR{NES2NVIoRjJ2MkS0OlEzRC:jPh?=
T-ALL	NGi3S4VCeG:ydH;zbZMhSXO\|YYm=	NG\qOFJj\XS5ZXXuJFEvPCCjbnSgOU4{KG2PIHH0JFI1cCCjbnSgNE46KGGwZDC1MlUhdU1iYYSgOFhpKGmwIHTp[oZmemWwdDDj[YxtKGyrbnW=	NGqwWW8zPCCxcjC0PIg>	MYfEUXNQ	NYqyc49R[W[oZXP0d{B1cGViUFmzT{Bx[XSqd3H5JIlvKFRvQVzMJINmdGxibHnu[ZM>	NXn1[oxHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSzNVA4OzZpPkK0N\|ExPzN4PD;hQi=>
H1975	M3jyUWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NYDOdWprOC5\|LUmuOu69VQ>?	NFHv[Is4Omh?	NGrmSo9FVVOR	MWTJR\|UxRTFwM{i1{txO	Ml7IQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR\|M{e4OFYoRjJ2M{O3PFQ3RC:jPh?=
H1975	NEmzeG5CeG:ydH;zbZMhSXO\|YYm=	NIf4SFIz\|ryP	M2DofVI1cA>?	M17OU2ROW09?	NUfMdHJUcW6lcnXhd4V{KGGyb4D0c5NqeyC{YYTlJJNq\26rZnnjZY51dHl?	M2rnVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{O3PFQ3Lz5{NEOzO\|g1PjxxYU6=
BON	M362OGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MmLGNU02\|ryP	M3\TU\|czcA>?		MYrk[YNz\WG\|ZYOgZ4VtdCCycn;sbYZmemG2aX;u	NXTkZm11RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS0OFM2OjNpPkK0OFQ{PTJ\|PD;hQi=>
BON	NGDIOnNCeG:ydH;zbZMhSXO\|YYm=	M2PUOFEuPc7:TR?=	MlrvNlRp		M4f4e4lv[3KnYYPld{BieG:ydH;zbZM>	NELNNXY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NES0N\|UzOyd-MkS0OFM2OjN:L3G+
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H522	M3:5NGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NHHPdmwyKM7:TR?=	MlXNO\|IhcA>?	MkjLSG1UVw>?	MmTUTY5pcWKrdIOgZ4VtdCCpcn;3eIg>	MnuwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV7M{eyPVkoRjJ3OUO3Nlk6RC:jPh?=
SKMES-1	NWLjVY5iS3m2b4TvfIlkKEG\|c3H5	NETEfmIyKM7:TR?=	M3fOR\|czKGh?		NIjyd4NKdmS3Y3XzJINmdGxiZHXheIg>	NWmyOldmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[wNVM{OThpPkK2NFE{OzF6PD;hQi=>
H596	NX\vXWFlTnWwY4Tpc44hSXO\|YYm=	NYm4WXY{OSEQvF2=			NXy2U3pPUW2yYXnyd{Bk\WyuIH3p[5JifGmxbh?=	MlPQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyMUOzNVgoRjJ4MEGzN\|E5RC:jPh?=
HCC2450	MWjGeY5kfGmxbjDBd5NigQ>?	NXfvbndROSEQvF2=			MortTY1x[Wm{czDj[YxtKGmwdnHzbY9v	MnvzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZyMUOzNVgoRjJ4MEGzN\|E5RC:jPh?=
HCT116	MkHlRY51cXC{b3zp[oVz[XSrdnWgZZN{[Xl?		NWDjWIR{PzJiaILz		M3jQfGFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgbJVu[W5iSFPUNVE3KGOnbHzzJIFnfGW{IEeyJIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTBiPTCwMlQ5KM7:TT6=	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTd4NUmwPUc,OjV5NkW5NFk9N2F-
MCF7	NHvLWJRCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NXzhR5BpPzJiaILz		MUPBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IHj1cYFvKE2FRkegZ4VtdHNiYX\0[ZIhPzJiaILzJIJ6KE2WVDDhd5NigSxiSVO1NEA:KDFizszNMi=>	NGDpbpk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe2OVkxQSd-MkW3OlU6ODl:L3G+
U87MG	NH\vdW9CdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		M3PpW\|czKGi{cx?=		NXq0eWVsSW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBpfW2jbjDVPFdOTyClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG\|c3H5MEBKSzVyIE2gNU43PCEQvF2u	M{TLTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3N{[1PVA6Lz5{NUe2OVkxQTxxYU6=
A549	NETYTppCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NGW4XXM4OiCqcoO=		MlzlRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCDNUS5JINmdGy\|IHHmeIVzKDd{IHjyd{BjgSCPVGSgZZN{[XluIFnDOVAhRSB{LkC3JO69VS5?	NGLPT2E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUe2OVkxQSd-MkW3OlU6ODl:L3G+
HeLa	MYfBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		M3rnV\|czKGi{cx?=		NIHGS2JCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JIh2dWGwIFjlUIEh[2WubIOgZYZ1\XJiN{KgbJJ{KGK7IF3UWEBie3OjeTygTWM2OCB;IESuN\|Qh\|ryPLh?=	NXGyZZN3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3OlU6ODlpPkK1O\|Y2QTB7PD;hQi=>
HCT116	MVfGeY5kfGmxbjDhd5NigQ>?	MYCxNEB2VQ>?	NIPXVoQyKGi{		NFHHOHJKdmirYnn0bY9vKG:oIGDJN2swSWu2IHnuJIh2dWGwIFjDWFEyPiClZXzsd{Bie3Onc4Pl[EBieyCDa4SgdIhwe3Cqb4L5cIF1cW:wIHH0JFExKHWPIHHmeIVzKDFiaIKgZpkhX2W\|dHXyckBjdG:2dHnu[{BidmGueYPpdy=>	NU\ZbY01RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW3OlU6ODlpPkK1O\|Y2QTB7PD;hQi=>
A2058 melanoma	NEDhfIdE\WyuIHP5Z4xmKGG\|c3H5	M4jPPFUhfU1?	M3vEfFI1KGi{cx?=		M1iwe2NmdGxiY4njcIUh[XK{ZYP0JIlvKGi3bXHuJGEzODV6IH3lcIFvd22jIHPlcIx{KGG\|c3Xzd4VlKGG\|IHHjZ5VufWyjdHnvckBifCCVdXLHNUBxcGG\|ZTDheEA2KHWPIHHmeIVzKDJ2IHjyd{BjgSCycn;wbYRqfW1iaX;kbYRmKHO2YXnubY5oKGKjc3XkJGZCS1NiYX7hcJl{cXN?	NUPkXHVtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki4Nlk2QTJpPkK4PFI6PTl{PD;hQi=>
A2058 melanoma	NXfyVlRqS2WubDDjfYNt\SCjc4PhfS=>	NUHvdFhlPSC3TR?=	NVK5Z3QxOjRiaILz		MW\D[YxtKGO7Y3zlJIFzemW\|dDDpckBpfW2jbjDBNlA2QCCvZXzhco9u[SClZXzsd{Bie3Onc4Pl[EBieyCjY3P1cZVt[XSrb36gZZQhTzJxTTDwbIF{\SCjdDC1JJVOKGGodHXyJFI1KGi{czDifUBxem:yaXTpeY0hcW:maXTlJJN1[WmwaX7nJIJie2WmIF\BR3Mh[W6jbInzbZM>	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQDh{OUW5Nkc,Ojh6Mkm1PVI9N2F-
SKOV3	MVHD[YxtKGO7Y3zlJIF{e2G7	M1zBOVIhfU1?	NYnueJc6OjRiaILz		NIf1UndE\WyuIHP5Z4xmKGG{cnXzeEBqdiCqdX3hckBUU0:YMzDj[YxteyCjc4Pld5Nm\CCjczDhZ4N2dXWuYYTpc44h[XRiR{KvUUBxcGG\|ZTDheEAzKHWPIHHmeIVzKDJ2IHjyd{BjgSCycn;wbYRqfW1iaX;kbYRmKHO2YXnubY5oKGKjc3XkJGZCS1NiYX7hcJl{cXN?	NHz4RoI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OEiyPVU6Oid-Mki4Nlk2QTJ:L3G+
SKOV3	NVrDSIJCS2WubDDjfYNt\SCjc4PhfS=>	NHz5ZZQzKHWP	M17qOVI1KGi{cx?=		NF:z[2JE\WyuIHP5Z4xmKGG{cnXzeEBqdiCqdX3hckBUU0:YMzDj[YxteyCjc4Pld5Nm\CCjczDhZ4N2dXWuYYTpc44h[XRiU4XiS\|EheGijc3WgZZQhOiC3TTDh[pRmeiB{NDDodpMh[nlicILvdIllcXWvIHnv[Ill\SC\|dHHpcolv\yCkYYPl[EBHSUOVIHHuZYx6e2m\|	NULjV2RQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMki4Nlk2QTJpPkK4PFI6PTl{PD;hQi=>
MDA-MB-231	MkTrR5l1d3SxeHnjbZR6KGG\|c3H5		NH7YVGo4OiCqcoO=		NXfxZpZpS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hVUSDLV3CMVI{OSClZXzsd{Bi\nSncjC3NkBpenNiYomgUXRVKGG\|c3H5MEBKSzVyIE2gNU45QCEQvF2u	NFW3bGQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUGwO\|QzQSd-MkmxNFc1Ojl:L3G+
PC3	NHzDTGNEgXSxdH;4bYNqfHliYYPzZZk>		M3[xTlczKGi{cx?=		NITSVndEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBRSzNiY3XscJMh[W[2ZYKgO\|IhcHK\|IHL5JG1VXCCjc4PhfUwhUUN3MDC9JFUvOzRizszNMi=>	M3z3VlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7MUC3OFI6Lz5{OUGwO\|QzQTxxYU6=
T47D	MnqzR5l1d3SxeHnjbZR6KGG\|c3H5		MYS3NkBpenN?		NITSNGdEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBVPDeGIHPlcIx{KGGodHXyJFczKGi{czDifUBOXFRiYYPzZZktKEmFNUCgQUA3Njl{IN88UU4>	M1XzSlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7MUC3OFI6Lz5{OUGwO\|QzQTxxYU6=
MCF7	NYrycG0xS3m2b4TvfIlkcXS7IHHzd4F6		M3u1eVczKGi{cx?=		NGjYdllEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBOS0Z5IHPlcIx{KGGodHXyJFczKGi{czDifUBOXFRiYYPzZZktKEmFNUCgQUAyOS5yNTFOwG0v	M4\hNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7MUC3OFI6Lz5{OUGwO\|QzQTxxYU6=
TC32	MYLxTHRUKGG\|c3H5				MnjBdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFSFM{KgZ4VtdHN?	MmH2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
A673	MWfxTHRUKGG\|c3H5				MVzxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSTZ5MzDj[Yxtew>?	Mn[2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
DAOY	NWPF[4NjeUiWUzDhd5NigQ>?				Mn\vdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKESDT2mgZ4VtdHN?	Ml;sQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Saos-2	NWq4R\|MyeUiWUzDhd5NigQ>?				M2H2UpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVYX;zMVIh[2WubIO=	NH;XVlc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
BT-37	NEnBeWxyUFSVIHHzd4F6				NYLlWmtVeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFLUMVM4KGOnbHzz	MnHxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
RD	NHK4bolyUFSVIHHzd4F6				MXPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWkRiY3XscJM>	M3PYeFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-SH	MUXxTHRUKGG\|c3H5				MnnJdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFONLV6tV2gh[2WubIO=	NF\xVZQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
BT-12	MknzdWhVWyCjc4PhfS=>				M2X4c5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCEVD2xNkBk\Wyucx?=	NH[3TpE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
MG 63 (6-TG R)	M1GxVZFJXFNiYYPzZZk>				NV;ZXoFDeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF3HJFY{KCh4LWTHJHIqKGOnbHzz	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
NB1643	NVGyRYVieUiWUzDhd5NigQ>?				MYTxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVkJzNkSzJINmdGy\|	NEO0NlQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
OHS-50	MnTqdWhVWyCjc4PhfS=>				NX7sdIY6eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF;IV{02OCClZXzsdy=>	Mn7EQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-SH	NGH1[lVyUFSVIHHzd4F6				NIPOOXlyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBUUy2QLWPIJINmdGy\|	NU\0OY5LRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh41	Ml65dWhVWyCjc4PhfS=>				MXvxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmh2MTDj[Yxtew>?	NX\DS5FsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
A673	MV;xTHRUKGG\|c3H5				MXHxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDBOlc{KGOnbHzzLS=>	M2X1UVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Rh30	MonsdWhVWyCjc4PhfS=>				NH;3R3ByUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUnizNEBk\Wyucx?=	MmrSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
MG 63 (6-TG R)	M2fuZZFJXFNiYYPzZZk>				M1\JO5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJG1IKDZ\|IDi2MXRIKFJrIHPlcIx{	MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Rh30	M1[xR5FJXFNiYYPzZZk>				MYPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDSbFMxKGOnbHzz	MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
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SK-N-MC	NGO3elFyUFSVIHHzd4F6				NWLiNJRleUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhW0tvTj3NR{Bk\Wyucx?=	NYXYZ29LRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
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insect	MXfGeY5kfGmxbjDhd5NigQ>?				MnniTY5pcWKrdHnvckBw\iC{ZXPvcYJqdmGwdDDoeY1idiCKaYOteIFo\2WmIIC4OYFteGijL4CxNVBidHCqYTDFOVQ2UyCvdYThcpQh\XiycnXzd4VlKGmwIHnud4VkfCClZXzsd{whUUN3MDC9JFAvODFzIN88UU4>	MlnXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzByM{S2NFcoRjNyMEO0OlA4RC:jPh?=
insect	MlXKSpVv[3Srb36gZZN{[Xl?				MXjJcohq[mm2aX;uJI9nKHKnY3;tZolv[W62IHj1cYFvKEircz30ZYdo\WRicEi1ZYxxcGFxcEGxNIFteGijIFW1OFJMKG23dHHueEBmgHC{ZYPz[YQhcW5iaX7z[YN1KGOnbHzzMEBKSzVyIE2gNE4xOjlizszNMi=>	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODB\|NE[wO{c,OzByM{S2NFc9N2F-
Sf21	MX\GeY5kfGmxbjDhd5NigQ>?		M2C5T\|EhcHJ?		NIDJS\|hKdmirYnn0bY9vKG:oIILlZ49u[mmwYX70JIh2dWGwIH\1cIwudGWwZ4ToJG4ufGW{bXnuZYwhUGm\|Nj30ZYdo\WRicEGxNIRmdHSjL4LlZ49u[mmwYX70JIh2dWGwIH\1cIwhdGWwZ4ToJJA5PWGucHjhJIV5eHKnc4Pl[EBqdiCkYXP1cI93cXK3czDpcoZm[3SnZDDT[lIyKGmwc3XjeEBk\WyuczD1d4lv\yCSSWCyJIF{KHO3YoP0doF1\SCvZXHzeZJm\CCjZoTldkAyKGi{IHL5JGFt\XijNkOzJHRz[WOncj3iZZNm\CCobIXvdoV{[2WwY3WgdI9t[XJuIFnDOVAhRSByLkGyOUDPxE1w	NEjqU409[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MECzOFYxPyd-M{CwN\|Q3ODd:L3G+
MCF7	MWHBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		M3[yNlczKGi{cx?=		MmDFRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCPQ1[3JINmdGy\|IHjhdoJwemmwZzDQTWs{S0FiRUW0OWshdXW2YX70JIFnfGW{IEeyJIhzeyCkeTDNWHQh[XO\|YYmsJGlEPTBiPTCwMlIxPiEQvF2u	M{j6eFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMEO0OlA4Lz5\|MECzOFYxPzxxYU6=
Sf21	Mo\sSpVv[3Srb36gZZN{[Xl?		NFzqOmQyKGi{		MkPXTY5pcWKrdHnvckBw\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>?	MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODB\|NE[wO{c,OzByM{S2NFc9N2F-
T47D	M1vEZWFvfGmycn;sbYZmemG2aY\lJIF{e2G7		NYnDemNoPzJiaILz		Ml3lRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDoeY1idiCWNEfEJINmdGy\|IHjhdoJwemmwZzDQTVNMS0FiSEGwOFdTKG23dHHueEBi\nSncjC3NkBpenNiYomgUXRVKGG\|c3H5MEBKSzVyIE2gNE4zQDZizszNMi=>	NWPpfZRCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CwN\|Q3ODdpPkOwNFM1PjB5PD;hQi=>
PC3	MnHWSpVv[3Srb36gZZN{[Xl?		M2jHe\|IhcHK\|		MWfJcohq[mm2aX;uJI9nKFCLM1ugbY4hcHWvYX6gVGM{KGOnbHzzJIF{e2W\|c3XkJIF{KHKnZIXjeIlwdiCrbjDBT3QheGixc4Doc5J6dGG2aX;uJIF1KFOnckS3N{Bu\WG\|dYLl[EBi\nSncjCyJIhzeyCkeTDmcJVwemW\|Y3XuZ4Uh[XO\|YYmsJGlEPTBiPTCwMlM3PSEQvF2u	NIO3N2s9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MECzOFYxPyd-M{CwN\|Q3ODd:L3G+
HT-29	NHfUUItE\WyuIHP5Z4xmKGG\|c3H5	M3jwU\|AvOTFzIITvJFMhfU1?	MnfCNlQhcHK\|		Mki4R4VtdCCleXPs[UBienKnc4SgbY4hcHWvYX6gTHQuOjliY3XscJMh[XO\|ZYPz[YQh[XNiYXPjeY12dGG2aX;uJIF1KEd{L12gdIhie2ViYYSgNE4yOTFidH:gN{B2VSCjZoTldkAzPCCqcoOgZpkheHKxcHnkbZVuKGmxZHnk[UB{fGGrbnnu[{Bj[XOnZDDmcI94KGO7dH;t[ZRzgQ>?	M4\DdVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMEO0OlA4Lz5\|MECzOFYxPzxxYU6=
A2058	NYnm[I5ITnWwY4Tpc44h[XO\|YYm=		NYm0WppFOSCqch?=		M2rwc2lvcGmkaYTpc44hd2ZiVF;SR\|IhcW5iaIXtZY4hSTJyNUigZ4VtdHNiYYPz[ZN{\WRiYYOg[IVkemWjc3WgbY4hWEuEL1HreEBxcG:\|cHjvdplt[XSrb36gZZQhW2W{NEezJIFnfGW{IEGgbJIh[nliV3XzeIVzdiCkbH;0JIFv[Wy7c3nzMEBKSzVyIE2gNE41OTZizszNMi=>	MlriQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzB\|NUmwNFMoRjNyM{W5NFA{RC:jPh?=
A2058	MUDGeY5kfGmxbjDhd5NigQ>?		NYLzSoFbOSCqch?=		NYT1NpRWUW6qaXLpeIlwdiCxZjDUU3JEOSCrbjDoeY1idiCDMkC1PEBk\WyuczDhd5Nme3OnZDDhd{Bl\WO{ZXHz[UBqdiCVNjDwbI9{eGixconsZZRqd25iYYSgV4VzOjN3L{KzOkBi\nSncjCxJIhzKGK7IGfld5Rmem5iYnzveEBidmGueYPpd{whUUN3MDC9JFAvPTV\|IN88UU4>	M{jlT\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyM{W5NFA{Lz5\|MEO1PVAxOzxxYU6=

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

Molarity Calculator

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

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04338399	Recruiting	Drug: Buparlisib & Paclitaxel	Head and Neck Cancer	Adlai Nortye Biopharma Co. Ltd.	December 12 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.
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 (KY 12420)

Wortmannin (KY 12420, SL-2052, BRN 0067676, NSC 627609) 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)