Carfilzomib (PR-171)

Name: Carfilzomib (PR-171)
Brand: Selleck Chemicals
SKU: S2853
Rating: 5 (148 reviews)

For research use only.

Catalog No.S2853

148 publications

CAS No. 868540-17-4

Carfilzomib (PR-171) is an irreversible proteasome inhibitor with IC50 of <5 nM in ANBL-6 cells, displayed preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, but little or no effect on the PGPH and T-L activities. Carfilzomib activates prosurvival autophagy and induces cell apoptosis.

Selleck's Carfilzomib (PR-171) has been cited by 148 publications

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

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Nature, 2020, 579(7797):136-140

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Nat Immunol, 2020, 10.1038/s41590-020-0697-2

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

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

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Cancer Cell, 2019, 35(5):752-766

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Cancer Cell, 2019, 36(5):498-511

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Nat Med, 2018, 24(3):292-303

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Nat Med, 2015, 10.1038/nm.3855

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Sci Adv, 2021, 7(23)eabg2697

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Autophagy, 2021, 1-14

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EMBO Rep, 2021, e52101

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Cell Rep, 2021, 34(11):108870

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J Control Release, 2021, S0168-3659(21)00126-7

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Haematologica, 2021, 10.3324/haematol.2021.278743

PubMed: 34162179 ( click the link to review the publication )

Cancers (Basel), 2021, 13(4)843

PubMed: 33671345 ( click the link to review the publication )

Cell Death Dis, 2021, 12(7):624

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Mol Cancer Ther, 2021, 20(2):367-378

PubMed: 33298585 ( click the link to review the publication )

Front Oncol, 2021, 11:631594

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Int J Mol Sci, 2021, 22(3)1341

PubMed: 33572814 ( click the link to review the publication )

Sci Rep, 2021, 11(1):2074

PubMed: 33483574 ( click the link to review the publication )

Hemasphere, 2021, 5(7):e602

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Biomedicines, 2021, 9(6)627

PubMed: 34072926 ( click the link to review the publication )

Oncol Rep, 2021, 45(4)34

PubMed: 33649855 ( click the link to review the publication )
Blood, 2020, 18 pii: blood

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Adv Sci (Weinh), 2020, 7(22):2002747

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Adv Sci (Weinh), 2020, 7(23):2001914

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Nat Commun, 2020, 22;11(1):1931

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Autophagy, 2020, 10.1080/15548627.2020.1740529

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Proc Natl Acad Sci U S A, 2020, 117(33):20004-20014

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Mol Syst Biol, 2020, 16(6):e9596

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Blood Cancer J, 2020, 10(12):125

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Int J Cancer, 2020, 10.1002/ijc.33046

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Int J Cancer, 2020, 10.1002/ijc.32976

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Oncogene, 2020, 9

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Cell Mol Life Sci, 2020, 10.1007/s00018-020-03568-x

PubMed: 32607595 ( click the link to review the publication )

Cancers (Basel), 2020, 11;12(5):E1207

PubMed: 32403415 ( click the link to review the publication )

FASEB J, 2020, 34(9):12379-12391

PubMed: 32960474 ( click the link to review the publication )

Front Immunol, 2020,

PubMed: 32903557 ( click the link to review the publication )

Cancer Sci, 2020, 111(4):1279-1290

PubMed: 32058648 ( click the link to review the publication )

Acta Pharmacol Sin, 2020, 10.1038/s41401-020-00544-w

PubMed: 33139838 ( click the link to review the publication )

J Electroanal Chem (Lausanne), 2020, 878:114733

PubMed: 33020701 ( click the link to review the publication )

Eur J Pharmacol, 2020, 870:172821

PubMed: 31770526 ( click the link to review the publication )

G3 (Bethesda), 2020, 4;10(5):1585-1597

PubMed: 32265286 ( click the link to review the publication )

SLAS Discov, 2020, 19;2472555220915851

PubMed: 32425084 ( click the link to review the publication )

Mol Biol Rep, 2020, 47(6):4849-4856

PubMed: 32424523 ( click the link to review the publication )

Iran J Pharm Res, 2020, 19(1):153-165

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Clin Cancer Res, 2020, clincanres.1232.2020

PubMed: 32669378 ( click the link to review the publication )
Blood Adv, 2020, 4(18):4312-4326

PubMed: 32915979 ( click the link to review the publication )

Autophagy, 2020, 1-13

PubMed: 32722981 ( click the link to review the publication )

Nat Chem Biol, 2020, 10.1038/s41589-020-0594-x

PubMed: 32747809 ( click the link to review the publication )

Br J Cancer, 2020, 10.1038/s41416-020-01191-y

PubMed: 33250513 ( click the link to review the publication )

Neurooncol Adv, 2020, 2(1):vdaa051

PubMed: 32642704 ( click the link to review the publication )

Oncotarget, 2020, 11(44):3984-3997

PubMed: 33216827 ( click the link to review the publication )

Cell Rep, 2020, 32(2):107897

PubMed: 32668248 ( click the link to review the publication )

J Zhejiang Univ Sci B, 2020, 21(1):64-76

PubMed: 31898443 ( click the link to review the publication )

Mol Cell, 2019, 75(4):849-858

PubMed: 31442425 ( click the link to review the publication )

Nat Chem Biol, 2019, 15(3):232-240

PubMed: 30692684 ( click the link to review the publication )

EMBO Mol Med, 2019, 11(10):e9930

PubMed: 31476112 ( click the link to review the publication )

Leukemia, 2019, 10.1038/s41375-019-0525-6

PubMed: 31358854 ( click the link to review the publication )

Cell Rep, 2019, 28(12):3224-3237

PubMed: 31533043 ( click the link to review the publication )

Cancers (Basel), 2019, 11(7)

PubMed: 31315220 ( click the link to review the publication )

PLoS Pathog, 2019, 15(1):e1007498

PubMed: 30645648 ( click the link to review the publication )

Cell Death Dis, 2019, 10(8):611

PubMed: 31406107 ( click the link to review the publication )

Arch Toxicol, 2019, 93(4):953-964

PubMed: 30863990 ( click the link to review the publication )

Cell Chem Biol, 2019, 10.1016/j.chembiol.2019.10.013

PubMed: 31735695 ( click the link to review the publication )

Cell Chem Biol, 2019, 26(3):340-351

PubMed: 30612952 ( click the link to review the publication )

Cell Physiol Biochem, 2019, 53(6):999-1014

PubMed: 31838790 ( click the link to review the publication )

Mol Cancer Ther, 2019, 18(11):2097-2110

PubMed: 31395684 ( click the link to review the publication )

Biochim Biophys Acta Mol Basis Dis, 2019, 1865(6):1666-1676

PubMed: 30954557 ( click the link to review the publication )

Amyloid, 2019, 26(1):24-33

PubMed: 30739503 ( click the link to review the publication )

Mol Cancer Res, 2019, 10.1158/1541-7786

PubMed: 31540997 ( click the link to review the publication )
Int J Mol Sci, 2019, 20(24)

PubMed: 31817163 ( click the link to review the publication )

Sci Rep, 2019, 9(1):18409

PubMed: 31804603 ( click the link to review the publication )

Sci Rep, 2019, 9(1):18062

PubMed: 31792264 ( click the link to review the publication )

Apoptosis, 2019, 24(5-6):404-413

PubMed: 30997620 ( click the link to review the publication )

Biochem J, 2019, 476(21):3211-3226

PubMed: 31652307 ( click the link to review the publication )

PLoS One, 2019, 14(12):e0225727

PubMed: 31794565 ( click the link to review the publication )

J Hematol Oncol, 2018, 11(1):112

PubMed: 30180865 ( click the link to review the publication )

Cancer Lett, 2018,

PubMed: 29410067 ( click the link to review the publication )

Cell Death Dis, 2018, 9(2):162

PubMed: 29415982 ( click the link to review the publication )

Mol Cancer Ther, 2018, 17(12):2610-2621

PubMed: 30224431 ( click the link to review the publication )

Hum Mol Genet, 2018, 27(3):451-462

PubMed: 29194514 ( click the link to review the publication )

Ann Hematol, 2018, 97(5):839-849

PubMed: 29359239 ( click the link to review the publication )

SLAS Discov, 2018, 23(5):459-473

PubMed: 29048950 ( click the link to review the publication )

Oncotarget, 2018,

PubMed: 29423101 ( click the link to review the publication )

Oncotarget, 2018, 9(29):20265-20281

PubMed: 29755650 ( click the link to review the publication )

FEBS J, 2018, 285(3):467-480

PubMed: 29211348 ( click the link to review the publication )

Blood, 2017, 5;129(1):88-99

PubMed: 27784673 ( click the link to review the publication )

Nat Commun, 2017, 8:14290

PubMed: 28134252 ( click the link to review the publication )

Clin Cancer Res, 2017, 23(16):4817-4830

PubMed: 28490465 ( click the link to review the publication )

Clin Cancer Res, 2017, 23(15):4301-4311

PubMed: 28314790 ( click the link to review the publication )

Exp Mol Med, 2017, 49(8):e365

PubMed: 28798402 ( click the link to review the publication )

Mol Cancer Ther, 2017, 16(11):2375-2386

PubMed: 28878026 ( click the link to review the publication )

Sci Rep, 2017, 7(1):8027

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J Pharmacol Exp Ther, 2017, 363(1):20-34

PubMed: 28760737 ( click the link to review the publication )
PLoS One, 2017, 12(2):e0173013

PubMed: 28235073 ( click the link to review the publication )

Leuk Lymphoma, 2017, 58(12):2916-2925

PubMed: 28509582 ( click the link to review the publication )

Cancer Metab, 2017, 5:7

PubMed: 28855983 ( click the link to review the publication )

Cell Host Microbe, 2017, 22(4):507-518

PubMed: 29024643 ( click the link to review the publication )

Nat Cell Biol, 2016, 18(8):897-909

PubMed: 27347849 ( click the link to review the publication )

EMBO J, 2016, 35(23):2602-2613

PubMed: 27789522 ( click the link to review the publication )

Leukemia, 2016, 30(1):104-11

PubMed: 26205085 ( click the link to review the publication )

Proc Natl Acad Sci U S A, 2016, 113(46):13162-13167

PubMed: 27799547 ( click the link to review the publication )

Matrix Biol, 2016, 55:22-34

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Cancer Lett, 2016, 382(1):1-10

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Cardiovasc Res, 2016, 110(2):188-99

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PLoS Pathog, 2016, 12(10):e1005929

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PLoS Genet, 2016, 12(9):e1006279

PubMed: 27588951 ( click the link to review the publication )

Bioinformatics, 2016, 32(12):i253-i261

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Leuk Lymphoma, 2016, 57(7):1677-86

PubMed: 26421357 ( click the link to review the publication )

Horm Cancer, 2016, 7(5-6):345-355

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Oncotarget, 2016, 7(47):77326-77341

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Oncotarget, 2016, 7(25):38523-38538

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Oncotarget, 2016, 7(4):4454-67

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Oncotarget, 2016, 7(2):1598-607

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Oncotarget, 2016, 7(29):45214-45224

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Oncotarget, 2016, 7(48):78883-78895

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Blood, 2015, 125(2):407-10

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Blood, 2015, 24;126(13):1565-74

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Blood , 2015, 10.1182/blood-2015-04-639542

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Leukemia, 2015, 29(6):1390-401

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Leukemia, 2015, 29(3):727-38

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Biomaterials, 2015, 73:70-84

PubMed: 26402156 ( click the link to review the publication )

J Clin Endocrinol Metab, 2015, 100(5):E697-709

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Cancer Discov, 2015, 5(9):972-87

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Br J Haematol, 2015, 171(3):378-86

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Med Oncol, 2015, 32(4):538

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PLoS One, 2015, 10(3):e0119546

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Chem Biol, 2015, 22(6):755-63

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Oncotarget, 2015, 6(19):17532-42

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Chem Biol, 2015, 10.1016/j.chembiol.2015.01.004

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Oncotarget, 2015, 6(10):8418-29

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Sci Transl Med, 2014, 6(250):250ra112

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Blood, 2014, 123(26):4120-31

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J Clin Invest, 2014, 124(12):5263-74

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Cancer Res, 2014, 74(16):4458-69

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Matrix Biol, 2014, 35:215-22

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Cancer Lett, 2014, 343(2):286-94

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Br J Haematol, 2014, 166(4):529-39

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J Virol, 2014, 87(23):13035-41

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Mol Cell Biol, 2014, 34(18):3421-34

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Cancer Biol Ther, 2014, 15(12):1646-57

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J Cancer, 2014, 4(8):614-25

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Am J Physiol Regul Integr Comp Physiol, 2014, 307(11):R1330-7

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Oncotarget, 2014, 5(14):5637-50

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Leuk Res, 2014, 38(8):970-6

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J Med Chem, 2013, 56(3):1262-75

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Purity & Quality Control

Choose Selective Proteasome Inhibitors

Biological Activity

Description

Targets

Proteasome ^[1]
(ANBL-6 cells)

5 nM

In vitro

Carfilzomib inhibits proliferation in a variety of cell lines and patient-derived neoplastic cells, including multiple myeloma, and induced intrinsic and extrinsic apoptotic signaling pathways and activation of c-Jun-N-terminal kinase (JNK). Carfilzomib reveals enhanced anti-MM activity compared with bortezomib, overcome resistance to bortezomib and other agents, and acts synergistically with dexamethasone (Dex). Carfilzomib shoes preferential in vitro inhibitory potency against the ChT-L activity in the β5 subunit, with over 80% inhibition at doses of 10 nM. Short exposure to low-dose Carfilzomib leads to preferential binding specificity for the β5 constitutive 20S proteasome and the β5i immunoproteasome subunits. Measurement of caspase activity in ANBL-6 cells pulsed with Carfilzomib reveals substantial increases in caspase-8, caspase-9, and caspase-3 activity after 8 hours, giving a 3.2-, 3.9- and 6.9-fold increase, respectively, over control cells after 8 hours. In carfilzomib pulse-treated cells, the mitochondrial membrane integrity is decreased to 41% (Q1 + Q2), compared with 75% in vehicle-treated control cells. ^[1] In another study, Carfilzomib has also shown preclinical effectiveness against hematological and solid malignancies. ^[2] Carfilzomib directly inhibits osteoclasts formation and bone resorption. ^[3]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Activity Description	PMID
MM.1S	M1vZR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MUKwMVExOCCwTR?=	NV\xfJRYPDhiaB?=	MVXJR\|UxyqB;wrCxNEBvVQ>?	M3GzcFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3M{GyOVQ{Lz5{NUOxNlU1OzxxYU6=
NCI-H929	NIH3RYNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M1rjcVAuOTByIH7N	M1TKZVQ5KGh?	M1TjUmlEPTBiPdMgNVQhdk1?	NWTzbGx3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWzNVI2PDNpPkK1N\|EzPTR\|PD;hQi=>
SUDHL16	NUXQXGVoSXCxcITvd4l{KEG\|c4PhfS=>	M4SwV\|IvPeLCk{OuOUBvVQ>?	NXzuWW1YPDhiaB?=	MmLa[Y5p[W6lZYOgeIhmKGOnbHyg[IVifGhiY3:teJJm[XSvZX70JJdqfGhiQVPZNVIyPQ>?	M4mxVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MkO5PVM2Lz5{NUKzPVk{PTxxYU6=
SUDHL14	NHrz[m5CeG:ydH;zbZMhSXO\|c3H5	MmTMNk426oDVMz61JI5O	M2Dhe\|Q5KGh?	Mmr0[Y5p[W6lZYOgeIhmKGOnbHyg[IVifGhiY3:teJJm[XSvZX70JJdqfGhiQVPZNVIyPQ>?	MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTJ\|OUmzOUc,OjV{M{m5N\|U9N2F-
U2932	NHf3b5BCeG:ydH;zbZMhSXO\|c3H5	MXyyMlXjiJN\|LkWgcm0>	MX20PEBp	NIO2T\|JmdmijbnPld{B1cGViY3XscEBl\WG2aDDjc{11emWjdH3lcpQhf2m2aDDBR3kyOjF3	MkW3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV{M{m5N\|UoRjJ3MkO5PVM2RC:jPh?=
P-UMSCC-1	M{ixbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			M{LENmlEPTB;MUGuNkBvVQ>?	M{TFRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUG1NFM6Lz5{NEmxOVA{QTxxYU6=
R-UMSCC-1	NYfOXmg4T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			MnXWTWM2OD1{Mkm0JI5O	M{i1RlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUG1NFM6Lz5{NEmxOVA{QTxxYU6=
P-Cal33	M4njPWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NUXJd2pOUUN3ME2xO{4{KG6P	MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlzNUCzPUc,OjR7MUWwN\|k9N2F-
R-Cal33	M{jvN2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NH3DR2xKSzVyPUGxNVIhdk1?	NVHvbXVLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NVUxOzlpPkK0PVE2ODN7PD;hQi=>
Jurkat	NEe5bmNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MVuxMVEydk1?	M4K4flQ5KGh?	NEPWcXRqdmirYnn0d{B1cGViY3XscEBxem:uaX\ldoF1cW:wIHPvMZRz\WG2bXXueEB4cXSqII\vdolvd3O2YYS=	NG\LU4o9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEiwNVEzQCd-MkS4NFEyOjh:L3G+
Jurkat	NGrkc49CeG:ydH;zbZMhSXO\|c3H5	M122Xlghdk1?	NHfWToIzPC92ODDo	NX3McJpbcW6mdXPld{BieG:ydH;zbZMtKGOjc4Dhd4Uh[WO2aY\heIlwdixiYX7kJHBCWlBiY3zlZZZi\2ViY3:teJJm[XSvZX70JJdqfGhidn;ybY5we3SjdB?=	NWXLNmpFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS4NFEyOjhpPkK0PFAyOTJ6PD;hQi=>
UMSCC-22A	MnrhRZBweHSxc3nzJGF{e3OjeR?=	MnLBNlAxKG6P	MX:yOEBp	NIXYSW5qdmS3Y3WgeIhmKGOnbHygZZBweHSxc3nzJINwNXS{ZXH0cYVvfCC5aYToJG9PYCByOUGy	MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjl{OUiwN{c,OjJ7Mkm4NFM9N2F-
UMSCC-22B	M2XpTWFxd3C2b4Ppd{BCe3O\|YYm=	MViyNFAhdk1?	NHfMdIQzPCCq	NVnORXk4cW6mdXPlJJRp\SClZXzsJIFxd3C2b4Ppd{Bkdy22cnXheI1mdnRid3n0bEBQVlhiMEmxNi=>	MomxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ7Mkm4NFMoRjJ{OUK5PFA{RC:jPh?=
1483	MVjBdI9xfG:\|aYOgRZN{e2G7	MnrhNlAxKG6P	MkXKNlQhcA>?	NVrIe4tXcW6mdXPlJJRp\SClZXzsJIFxd3C2b4Ppd{Bkdy22cnXheI1mdnRid3n0bEBQVlhiMEmxNi=>	MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjl{OUiwN{c,OjJ7Mkm4NFM9N2F-
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MDA-MB-468	NE[1[pRHfW6ldHnvckBie3OjeR?=	MUCzOUBvVQ>?	M2rDZVQhcHK\|	Mn:yTY5pcWKrdHnvckBw\iB{NmOgdJJwfGWjc3;t[UBqdiCqdX3hckBOTEFvTVKtOFY5KGOnbHzzJIF{e2W\|c3XkJIF{KGGlY4XteYxifGmxbjDv[kBpcWeqIH3vcIVkfWyjcjD3[YlocHRicH;sfZVjcXG3aYTpck1kd26sdXfheIVlKHC{b4TlbY5{KGG2IEO1JI5OKGGodHXyJFQhcHK\|IHL5JHdme3Sncn6gZoxwfCCjbnHsfZNqew>?	NEDFfY09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{m5OFc{PCd-Mke5PVQ4OzR:L3G+
MM1S	MlzQR5l1d3SxeHnjbZR6KGG\|c3H5		NVLwS2dSPzJiaILz	MlnzR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUW0yWyClZXzsd{Bu\WG\|dYLl[EBi\nSncjC3NkBpenNiYomgUXRUKGG\|c3H5MEBKSzVyIE2gNE4xODF3IN88UU4>	MmKzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjhyMke1N\|EoRjJ6MEK3OVMyRC:jPh?=
RPMI8226	NYLqZXV2S3m2b4TvfIlkcXS7IHHzd4F6		M3;he\|czKGi{cx?=	MWHDfZRwfG:6aXPpeJkh[WejaX7zeEBpfW2jbjDSVG1KQDJ{NjDj[YxteyCvZXHzeZJm\CCjZoTldkA4OiCqcoOgZpkhVVSVIHHzd4F6NCCLQ{WwJF0hOC5yMUOyJO69VS5?	MonUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjhyMke1N\|EoRjJ6MEK3OVMyRC:jPh?=
TC32	MnyzdWhVWyCjc4PhfS=>			NFXyN2xyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiVFOzNkBk\Wyucx?=	M4DubFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
U-2 OS	NVzMeIw3eUiWUzDhd5NigQ>?			M4Wye5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCXLUKgU3Mh[2WubIO=	NIjDOZY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
A673	NVTF[ZBOeUiWUzDhd5NigQ>?			NUjRXXlUeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFG2O\|Mh[2WubIO=	NHn6UG09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
DAOY	NHTiU4dyUFSVIHHzd4F6			MWXxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhTEGRWTDj[Yxtew>?	M1fzXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Saos-2	Mn\1dWhVWyCjc4PhfS=>			MV;xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW2Gxcz2yJINmdGy\|	NInmdIM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
BT-37	NFPEcFByUFSVIHHzd4F6			M3jZO5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCEVD2zO{Bk\Wyucx?=	MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
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SK-N-SH	NWHrSm1MeUiWUzDhd5NigQ>?			NV\TWWpkeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPLMW4uW0hiY3XscJM>	M3nreVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
BT-12	NHW5XYtyUFSVIHHzd4F6			MV3xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSlRvMUKgZ4VtdHN?	M3z0SVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
MG 63 (6-TG R)	NFrmZWJyUFSVIHHzd4F6			MXzxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVUdiNkOgLFYuXEdiUjmgZ4VtdHN?	MlHuQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
NB1643	NFeyN5pyUFSVIHHzd4F6			MW\xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVkJzNkSzJINmdGy\|	M{SyfFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
OHS-50	NELk[o9yUFSVIHHzd4F6			NYfv[4F{eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF;IV{02OCClZXzsdy=>	MmnHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
BT-12	NVflW3RieUiWUzDhd5NigQ>?			Mlm3dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgRnQuOTJiY3XscJM>	M1O0OVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
LAN-5	Ml7ldWhVWyCjc4PhfS=>			NYXrcGZReUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhVEGQLUWgZ4VtdHN?	MnnMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
fibroblast cells	MoXydWhVWyCjc4PhfS=>			MnzudWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKGOxboTyc4whUGhid3ns[EB1gXCnIH\pZpJw[myjc4SgZ4VtdHN?	NF24WFg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB-EBc1	MXTxTHRUKGG\|c3H5			NEX1bXpyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBPSi2HQnOxJINmdGy\|	MkfSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-SH	MWLxTHRUKGG\|c3H5			MXrxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDTT{1PNVOKIHPlcIx{	MkPKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Rh41	M33NTpFJXFNiYYPzZZk>			M1rPPZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaESxJINmdGy\|	NGfTXos9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
A673	Ml\PdWhVWyCjc4PhfS=>			MoezdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgRVY4OyClZXzsd{k>	NXPyTopLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh30	NWWxUVg6eUiWUzDhd5NigQ>?			MWDxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmh\|MDDj[Yxtew>?	M1T0RVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
BT-37	MkPWdWhVWyCjc4PhfS=>			Mo\mdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohS2:wZnnycYF1d3K7IIPjdoVmdiCob4KgRnQuOzdiY3XscJM>	NV\CVXF6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
MG 63 (6-TG R)	NF\ue3ByUFSVIHHzd4F6			MXXxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDNS{A3OyBqNj3US{BTMSClZXzsdy=>	MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Rh30	MlfKdWhVWyCjc4PhfS=>			M4\Y[ZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHJpOzBiY3XscJM>	NWTpOZRSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
fibroblast cells	NWPOTWpteUiWUzDhd5NigQ>?			M{Pue5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJINwdnS{b3ygTIghf2muZDD0fZBmKG[rYoLvZoxie3RiY3XscJM>	NUjrc4h1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
OHS-50	NGm1XWpyUFSVIHHzd4F6			NVTQdYFieUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiQ3;u[olzdWG2b4L5JJNkemWnbjDmc5IhV0iVLUWwJINmdGy\|	MnezQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-SH	NHnUbIJyUFSVIHHzd4F6			NFHZ[mlyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCRcoToc4dwdmGuIEPEJJZq[WKrbHn0fUB{[3KnZX6g[o9zKFONLV6tV2gh[2WubIO=	MnTkQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Daoy	Mkn6dWhVWyCjc4PhfS=>			MVnxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBQenSqb3fvcoFtKDOGII\pZYJqdGm2eTDzZ5Jm\W5iZn;yJGRid3liY3XscJM>	MlXJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
TC32	M3;XdJFJXFNiYYPzZZk>			NG\hNJhyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCRcoToc4dwdmGuIEPEJINie3Cjc3Wgd4Nz\WWwIH\vdkBVSzN{IHPlcIx{	NV7H[5M1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
TC32	MnO0dWhVWyCjc4PhfS=>			MVHxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBQenSqb3fvcoFtKDOGII\pZYJqdGm2eTDzZ5Jm\W5iZn;yJHREOzJiY3XscJM>	MmLSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
MG 63 (6-TG R)	NHTBRpVyUFSVIHHzd4F6			NXvNZlhZeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiT4L0bI9od26jbDCzSEB3cWGkaXzpeJkhe2O{ZXXuJIZweiCPRzC2N{ApPi2WRzDSLUBk\Wyucx?=	MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SJ-GBM2	NVziR3JpeUiWUzDhd5NigQ>?			NFmyRXpyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1qtS2JOOiClZXzsdy=>	NGT3bW89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SK-N-MC	NGnkXWlyUFSVIHHzd4F6			NIO3bZpyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1utUk1OSyClZXzsdy=>	Mn:xQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
NB-EBc1	MkL0dWhVWyCjc4PhfS=>			MmiwdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6ELVXCZ\|Eh[2WubIO=	NEHlbXM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
LAN-5	M3HwW5FJXFNiYYPzZZk>			NGLp[oJyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTFHOMVUh[2WubIO=	NUXFTYt2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh18	M1;3fpFJXFNiYYPzZZk>			M1LBc5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaEG4JINmdGy\|	NI[2e4M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SK-N-MC	NIjueoxyUFSVIHHzd4F6			M1zCVJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHNMNU5vTVOgZ4VtdHN?	MmPUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SJ-GBM2	MXzxTHRUKGG\|c3H5			M{DYbZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHNLNUeETUKgZ4VtdHN?	NIfNfm49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
TC32	M{K3[JFJXFNiYYPzZZk>			M2ruT5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KEOxbn\pdo1ifG:{eTDzZ5Jm\W5iZn;yJHREOzJiY3XscJM>	NFHoWFM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
Rh18	M37JVpFJXFNiYYPzZZk>			MYDxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBEd26oaYLtZZRwenlic3Py[YVvKG[xcjDSbFE5KGOnbHzz	NWXFSm8{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Saos-2	NHfzeZNyUFSVIHHzd4F6			NHW5VW9yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCFb37mbZJu[XSxcomgd4Nz\WWwIH\vdkBU[W:\|LUKgZ4VtdHN?	M2Pnc\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SJ-GBM2	MkLqdWhVWyCjc4PhfS=>			M3q5dpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KE:{dHjv[49v[WxiM1Sgeoli[mmuaYT5JJNkemWnbjDmc5IhW0pvR1LNNkBk\Wyucx?=	NEDIV\|c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
RD	M3rxRZFJXFNiYYPzZZk>			Mkf1dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohV3K2aH;nc45idCB\|RDD2bYFjcWyrdImgd4Nz\WWwIH\vdkBTTCClZXzsdy=>	NGGxOlE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
ANBL-6	M3POcWZ2dmO2aX;uJIF{e2G7			NFPxVHpKdmirYnn0bY9vKG:oIEKwV{Bxem:2ZXHzc41mKGGldHn2bZR6KGmwIHj1cYFvKEGQQlytOkBk\WyuczygTWM2OCB;IECuNFEh\|ryPLh?=	MlPWQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl4NUKxOFMoRjJ7NkWyNVQ{RC:jPh?=
MCF7	NXn6SnpnS3m2b4TvfIlkcXS7IHHzd4F6		NET6fFM1QCCqcoO=	M37yfGN6fG:2b4jpZ4l1gSCjZ3HpcpN1KGi3bXHuJG1ETjdiY3XscJMh[W[2ZYKgOFghcHK\|IHL5JG1VXCCjc4PhfUwhUUN3MDC9JFAvODB2MTFOwG0v	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODF4NUO0OEc,OzBzNkWzOFQ9N2F-
MDA-MB-231	MVzDfZRwfG:6aXPpeJkh[XO\|YYm=		M3vXdlQ5KGi{cx?=	MoTwR5l1d3SxeHnjbZR6KGGpYXnud5QhcHWvYX6gUWRCNU2ELUKzNUBk\WyuczDh[pRmeiB2ODDodpMh[nliTWTUJIF{e2G7LDDJR\|UxKD1iMD6wNFQ1KM7:TT6=	MkjBQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzBzNkWzOFQoRjNyMU[1N\|Q1RC:jPh?=
RPMI8226	NFr4b\|REgXSxdH;4bYNqfHliYYPzZZk>		NWX0RVFXPDhiaILz	NUXBO\|NIS3m2b4TvfIlkcXS7IHHnZYlve3RiaIXtZY4hWlCPSUiyNlYh[2WubIOgZYZ1\XJiNEigbJJ{KGK7IF3UWEBie3OjeTygTWM2OCB;IECuNFA3PyEQvF2u	MmnlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOzBzNkWzOFQoRjNyMU[1N\|Q1RC:jPh?=

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	pERK / ERK / pSTAT5 / STAT5 / pPI3K / PI3K; PubMed: 24590311 Oncogenesis Western blot analysis for activated (phosphorylated) ERK, Stat5 and PI3K signaling pathways following exposure to carfilzomib, total levels of ERK, Stat5 and PI3K were used as a loading control. caspase-9 / caspase-8; PubMed: 24590311 Oncogenesis Western blot analysis for activated (cleaved) caspase-8 and caspase-9 following exposure to carfilzomib. c-PARP / PARP / caspase-3; PubMed: 22929803 Clin Cancer Res UMSCC-22A, UMSCC-22B, 1483 and UMSCC-1 cells were treated for 24 hours with 0.1% DMSO, or 200 nmol/L carfilzomib or ONX 0912, followed by immunoblotting with anti-PARP, anti-caspase-3, or anti-β-actin. Shown are full-length PARP, cleaved PARP (c-PARP), and the cleaved, active subunits of caspase-3. Similar results were obtained in 3 independent experiments. Bcl-2 / Bcl-Xl / Mcl-1 / Bik / Bim / Bax / Bak; PubMed: 22929803 Clin Cancer Res UMSCC-22A, UMSCC-22B, 1483 and UMSCC-1 cells were treated for 24 hours with 0.1% DMSO, or 100 nmol/L carfilzomib or ONX 0912, followed by immunoblotting for the indicated proteins. In the case of Bik immunoblotting, cells were treated with 200 nmol/L carfilzomib or ONX 0912 to more clearly demonstrate Bik upregulation in 1483 and UMSCC-1 cells. Blots shown are representative of 3 independent experiments. Atg5 / Atg12 / Beclin-1 / LC3-II; PubMed: 22929803 Clin Cancer Res HNSCC cells were treated for 24 hours with 100 nmol/L carfilzomib or ONX 0912, or with 0.1% DMSO. Immunoblots were probed for Beclin-1, Atg5/12 conjugate, LC3-II, or β-actin. Representative blots from 3 independent experiments are shown. Noxa / Bik / Puma / Mcl-1; PubMed: 25548100 Mol Cancer Res SW620 cells were treated with the indicated dosage for 48 h. Expression of Noxa, Bik and/or Puma, c-myc and Mcl-1 proteins was then analyzed by immunoblotting. Tubulin served as control for protein loading. EGFR / HER2 / ER alpha / p-Akt(Ser473) / Akt / p-ERK / ERK / p53; PubMed: 29069787 Oncotarget T47D and MCF7 cells were cultured with the indicated carfilzomib concentrations for 32 or 36 hours, respectively. Western blots of protein lysates were probed with the indicated antibodies. β-actin served as loading control. BDP1 / HER2(Tyr1248) / HER2(Tyr1221/Tyr1222) / PARP1 / caspase-7 / p53 Mut; PubMed: 29069787 Oncotarget BT474 cells were cultured in the presence of the indicated carfilzomib concentrations for 32 hours. Western blots of protein lysates were probed with the indicated antibodies. HLA class I; PubMed: 26323098 Oncotarget Immunofluorescence analysis was performed to confirm the consequence that down-regulation of HLA class I was in a dose- and time-dependent manner.	24590311 22929803 25548100 29069787 26323098
Growth inhibition assay	Cell viability; PubMed: 27655642 Oncotarget Cytotoxic effects of carfilzomib on breast cancer cells in MTT assays. Seven human breast cancer cell lines, MCF7, T-47D, MDA-MB-361, HCC1954, MDA-MB-468, MDA-MB-231, and BT-549 were treated with carfilzomib at 0, 0.001 μM, 0.01 μM, 0.05 μM, 0.1 μM, 1 μM, 10 μM, or 50 μM for 72 h, then subjected to MTT assays. The absorbance of each well was measured at 540 nm and plotted for the cell viability curve. IC50 values of carfilzomib in breast cancer cell lines were listed.	27655642

In vivo

Carfilzomib moderately reduces tumor growth in an in vivo xenograft model. Carfilzomib effectively decreases multiple myeloma cell viability following continual or transient treatment mimicking. Carfilzomib increases trabecular bone volume, decreases bone resorption and enhances bone formation in non-tumor bearing mice. ^[3]

Protocol

Kinase Assay:^[1]	- Collapse Enzyme-linked immunosorbent assay for subunit profiling of carfilzomib: ANBL-6 cells (2 × 10⁶/well) are plated in 96-well plates and treated with Carfilzomib doses from 0.001 to 10 μM for 1 hour. Cells are then lysed (20 mM Tris-HCl, 0.5 mM EDTA), and cleared lysates are transferred to polymerase chain reaction (PCR) plates. A standard curve is generated using untreated ANBL-6 cell lysates starting at a concentration of 6 μg protein/μL. The active site probe [biotin-(CH2)4-Leu-Leu-Leu-epoxyketone; 20 μM] is added and incubated at room temperature for 1 hour. Cell lysates are then denatured by adding 1% sodium dodecyl sulfate (SDS) and heating to 100°C, followed by mixing with 20 μL per well streptavidin-sepharose high-performance beads in a 96-well multiscreen DV plate and incubated for 1 hour. These beads are then washed with enzyme-linked immunosorbent assay (ELISA) buffer (PBS, 1% bovine serum albumin, and 0.1% Tween-20), and incubated overnight at 4°C on a plate shaker with antibodies to proteasome subunits. Antibodies used included mouse monoclonal anti-β1, anti-β2, anti-β1i, and anti-β5i, goat polyclonal anti-β2i, and rabbit polyclonal anti-β5 (affinity-purified antiserum against KLH-CWIRVSSDNVADLHDKYS peptide). The beads are washed and incubated for 2 hours with horseradish peroxidase-conjugated secondary goat antirabbit, goat antimouse or rabbit antigoat antibodies. After washing, the beads are developed using the supersignal ELISA picochemiluminescence substrate. Luminescent detection is performed. Raw luminescence is converted to μg/mL by comparison with the standard curve and expressed as the % inhibition relative to vehicle control. Curve fits are generated using the following nonsigmoidal dose-response equation: Y = Bottom + (Top-Bottom)/(1 + 10̂((LogEC50 − X) × HillSlope)), where X is the logarithm of concentration, Y is the % inhibition, and EC50 is the dose showing 50% effect.
Cell Research:^[1]	- Collapse Cell lines: WST-1, ANBL-6 cells Concentrations: 100 nM Incubation Time: 1 hour Method: WST-1 is used to determine the effects of proteasome inhibitor Carfilzomib on cell proliferation. The inhibition of proliferation is calculated in relation to parallel control cells that receives vehicle alone. A linear spline function is used to interpolate the median inhibitory concentration (IC50) using XLfit 4 software. The degree of resistance (DOR) is calculated using the formula: DOR = IC50(resistant cells)/IC50(sensitive cells). ANBL-6 cells pulsed with 100 nM carfilzomib are washed and suspended in PBS containing 5 μg/mL of JC-1, which exhibits potential-dependent accumulation in mitochondria. Analysis of the mitochondrial membrane potential-dependent color shift from 525 to 590 nm is carried out on a FacScan, and the data are analyzed with CellQuest software. (Only for Reference)
Animal Research:^[4]	- Collapse Animal Models: Beige-nude-XID mice Dosages: 2.0 mg/kg Administration: i.v. (Only for Reference)

References

[4] Dasmahapatra G, et al. Mol Cancer Ther. 2011, 10(9), 1686-1697.

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Solubility (25°C)

In vitro	DMSO	50 mg/mL (69.45 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 2% DMSO+30% PEG 300+2%Tween 80+ddH2O For best results, use promptly after mixing.	1mg/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 Carfilzomib (PR-171) SDF

Molecular Weight	719.91
Formula	C₄₀H₅₇N₅O₇
CAS No.	868540-17-4
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CC(C)CC(C(=O)C1(CO1)C)NC(=O)C(CC2=CC=CC=C2)NC(=O)C(CC(C)C)NC(=O)C(CCC3=CC=CC=C3)NC(=O)CN4CCOCC4

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage

mg/kg

Average weight of animals

Dosing volume per animal

Number of animals

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO+ % + % Tween 80+ % ddH₂O

Calculate Reset

Calculation results:

Working concentration： mg/ml；

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

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

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

Bio Calculators

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and SDS / COA (available on product pages).

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration _(start) x Volume _(start) = Concentration _(final) x Volume _(final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and SDS / COA (available online).

The Serial Dilution Calculator Equation

Serial Dilutions
Concertration (start):
Dilution-folds:

Computed Result

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

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
NCT04811508	Recruiting	--	Relapsed Multiple Myeloma	Centre Hospitalier le Mans	August 4 2020	--
NCT04407858	Recruiting	--	Myeloma\|Heart Failure\|Hypertension	European Georges Pompidou Hospital	May 21 2020	--

Tech Support

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

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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

Frequently Asked Questions

Question 1:
How should I prepare solution of Carfilzomib for ongoing in vivo study?
Answer:
This compound can be dissolved in 2% DMSO/30% PEG 300/dd H2O at 10 mg/ml as a suspension, and can be dissolved in 2% DMSO/ castor oil at 10 mg/ml as a clear solution.

Proteasome Signaling Pathway Map

Proteasome Inhibitors with Unique Features

Pan Proteasome Inhibitor

Ixazomib (MLN2238) : β5 site, IC50=3.4 nM; β1 site, IC50=31 nM; β2 site, IC50=3500 nM.
Most Potent Proteasome Inhibitor

Bortezomib (PS-341) : 20S proteasome, K_i of 0.6 nM.
Newest Proteasome Inhibitor

Oprozomib (ONX 0912) : Orally bioavailable inhibitor for CT-L activity of 20S proteasome β5/LMP7 with IC50 of 36 nM/82 nM.
Classic Proteasome Inhibitor

ONX-0914 (PR-957) : Selective immunoproteasome inhibitor with minimal cross-reactivity for the constitutive proteasome.

Related Proteasome Products

VR23 ^New

VR23 is a potent proteasome inhibitor with IC50 of 1 nM, 50-100 nM, and 3 μM for trypsin-like proteasomes, chymotrypsin-like proteasomes, and caspase-like proteasomes, respectively.
Calpeptin ^New

Calpeptin is a potent, cell-permeable calpain inhibitor with ID50 of 52 nM, 34 nM, 138 nM, and 40 nM for Calpain I (porcine erythrocytes), Calpain II (porcine kidney), Papainb, and Calpain I (human platelets), respectively. Calpeptin attenuates apoptosis and intracellular inflammatory changes in muscle cells.
Marimastat (BB-2516) ^New

Marimastat (BB-2516, TA2516) is a broad spectrum matrix metalloprotease (MMP) inhibitor for MMP-9, MMP-1, MMP-2, MMP-14 and MMP-7 with IC50 of 3 nM, 5 nM, 6 nM, 9 nM and 13 nM, respectively. Phase 3.
MG-132

MG132 (Z-Leu-Leu-Leu-al) is a potent cell-permeable proteasome and calpain inhibitor with IC50s of 0.1 μM and 1.2 μM for the inhibition of proteasome and calpain, respectively. MG132 activates autophagy and induces apoptosis in tumor cells.
Bortezomib (PS-341)

Bortezomib (PS-341, Velcade, LDP-341, MLM341, NSC 681239) is a potent 20S proteasome inhibitor with K_i of 0.6 nM. It exhibits favorable selectivity towards tumor cells over normal cells. Bortezomib (PS-341) inhibits NF-κB and induces ERK phosphorylation to suppress cathepsin B and inhibit the catalytic process of autophagy in ovarian cancer and other solid tumors.
Ixazomib (MLN2238)

Ixazomib (MLN2238) inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50 and K_i of 3.4 nM and 0.93 nM in cell-free assays, respectively, also inhibits the caspase-like (β1) and trypsin-like (β2) proteolytic sites, with IC50 of 31 and 3500 nM. Ixazomib (MLN2238) induces autophagy. Phase 3.

Features:A first-in-class proteasome inhibitor that has improved pharmacokinetics (PK), pharmacodynamics(PD), and antitumor activity in preclinical studies.
ONX-0914 (PR-957)

ONX-0914 (PR-957) is a potent and selective immunoproteasome inhibitor with minimal cross-reactivity for the constitutive proteasome in a cell-free assay.

Features:The first highly selective, small molecule inhibitor of the immunoproteasome. Potential use in cancer and autoimmune diseases (e.g. rheumatoid arthritis, inflammatory bowel disease, and lupus).
Ixazomib Citrate (MLN9708) Analogue

Ixazomib Citrate (MLN9708) Analogue is the analogue of Ixazomib Citrate (MLN9708) from WO2016165677A1. Ixazomib Citrate (MLN9708) immediately hydrolyzed to Ixazomib (MLN2238), the biologically active form, on exposure to aqueous solutions or plasma. Ixazomib (MLN2238) inhibits the chymotrypsin-like proteolytic (β5) site of the 20S proteasome with IC50/K_i of 3.4 nM/0.93 nM in cell-free assays, less potent to β1 and little activity to β2. Ixazomib (MLN2238) induces autophagy. Phase 3.

Features:The 1st oral proteasome inhibitor in early stage clinical trials for Multiple Myeloma.
Celastrol (NSC 70931)

Celastrol (NSC 70931, Tripterine) is a potent proteasome inhibitor for the chymotrypsin-like activity of a purified 20S proteasome with IC50 of 2.5 μM. Celastrol induces apoptosis and autophagy via the ROS/JNK signaling pathway. Celastrol inhibits dopaminergic neuronal death of Parkinson's disease through activating mitophagy.

Features:A potent antioxidant and anti-inflammatory drug.
Oprozomib (ONX 0912)

Oprozomib (ONX 0912, PR-047) is an orally bioavailable inhibitor for CT-L activity of 20S proteasome β5/LMP7 with IC50 of 36 nM/82 nM. Phase 1/2.

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Carfilzomib (PR-171)