AZD1480

Name: AZD1480
Brand: Selleck Chemicals
SKU: S2162
Rating: 5 (90 reviews)

For research use only.

Catalog No.S2162

90 publications

CAS No. 935666-88-9

AZD1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of 0.26 nM in a cell-free assay, selectivity against JAK3 and Tyk2, and to a smaller extent against JAK1. Phase 1.

Selleck's AZD1480 has been cited by 90 publications

Cell Stem Cell, 2019, 25(1):69-86

PubMed: 31080136 ( click the link to review the publication )

Cell, 2018, 175(2):458-471

PubMed: 30173917 ( click the link to review the publication )

Cancer Cell, 2018, 34(2):315-330

PubMed: 30033091 ( click the link to review the publication )

Cell Metab, 2017, 25(6):1320-1333

PubMed: 28591635 ( click the link to review the publication )

Nat Med, 2015, 21(1):47-54

PubMed: 25485912 ( click the link to review the publication )

Blood Cancer J, 2021, 11(6):111

PubMed: 34099621 ( click the link to review the publication )

Cancers (Basel), 2021, 13(6)1205

PubMed: 33801977 ( click the link to review the publication )

Cancers (Basel), 2021, 13(7)1579

PubMed: 33808059 ( click the link to review the publication )

Cancers (Basel), 2021, 13(15)3780

PubMed: 34359681 ( click the link to review the publication )

Aging (Albany NY), 2021, 13(10):13644-13662

PubMed: 33893245 ( click the link to review the publication )

Evid Based Complement Alternat Med, 2021, 2021:5591687

PubMed: 34211571 ( click the link to review the publication )

NPJ Precis Oncol, 2021, 5(1):75

PubMed: 34376782 ( click the link to review the publication )

Proc Natl Acad Sci U S A, 2020, 117(26):15047-15054

PubMed: 32532922 ( click the link to review the publication )

PLoS Biol, 2020, 18(3):e3000646

PubMed: 32203518 ( click the link to review the publication )

Clin Cancer Res, 2020,

PubMed: 32887724 ( click the link to review the publication )

Front Immunol, 2020, 14;11:867

PubMed: 32477351 ( click the link to review the publication )

Carcinogenesis, 2020, 41(7):993-1004

PubMed: 31740922 ( click the link to review the publication )

Oncogenesis, 2020, 10;9(2):15

PubMed: 32041943 ( click the link to review the publication )

Mol Cancer Res, 2020, molcanres.0186.2020

PubMed: 33004621 ( click the link to review the publication )

J Immunother Cancer, 2020, 8(1):e000285

PubMed: 32581055 ( click the link to review the publication )

Eur Arch Otorhinolaryngol, 2020, 10.1007/s00405-020-06274-3

PubMed: 32783069 ( click the link to review the publication )

Nat Commun, 2019, 10(1):716

PubMed: 30755611 ( click the link to review the publication )

Nat Commun, 2019, 10(1):3601

PubMed: 31399589 ( click the link to review the publication )

Cancer Res, 2019, 10.1158/0008-5472.CAN-18-2808

PubMed: 31806641 ( click the link to review the publication )
Oncogene, 2019, 101038/s41388-019-1136-4

PubMed: 31804622 ( click the link to review the publication )

J Exp Clin Cancer Res, 2019, 18;38(1):85

PubMed: 30777101 ( click the link to review the publication )

Cancers (Basel), 2019, 11(1)

PubMed: 30634502 ( click the link to review the publication )

Cancers (Basel), 2019, 11(9)

PubMed: 31540495 ( click the link to review the publication )

Cell Death Discov, 2019, 5:72

PubMed: 30854231 ( click the link to review the publication )

Cancer Discov, 2019,

PubMed: 30366930 ( click the link to review the publication )

Front Immunol, 2019, 1.1243055556

PubMed: 31156620 ( click the link to review the publication )

Gastric Cancer, 2019, 22(3):486-496

PubMed: 30264329 ( click the link to review the publication )

Stem Cell Res Ther, 2019, 10(1):384

PubMed: 31842997 ( click the link to review the publication )

J Cell Mol Med, 2019, 23(6):4301-4312

PubMed: 30993883 ( click the link to review the publication )

Lab Invest, 2019, 99(12):1810-1821

PubMed: 31467427 ( click the link to review the publication )

Am J Physiol Lung Cell Mol Physiol, 2019, 316(3):L487-L497

PubMed: 30604628 ( click the link to review the publication )

Acta Pharmacol Sin, 2019, 10.1038/s41401-019-0254-4

PubMed: 31201357 ( click the link to review the publication )

J Microbiol Biotechnol, 2019, 29(12):2006-2013

PubMed: 31581384 ( click the link to review the publication )

FEBS Open Bio, 2019, 9(10):1689-1704

PubMed: 31314158 ( click the link to review the publication )

Reproduction, 2019, 158(4):303-312

PubMed: 31408846 ( click the link to review the publication )

Cancer Immunol Res, 2019,

PubMed: 30401677 ( click the link to review the publication )

Nat Commun, 2018, 9(1):4345

PubMed: 30341316 ( click the link to review the publication )

Cancer Lett, 2018, 429:54-65

PubMed: 29729901 ( click the link to review the publication )

Metabolism, 2018, 79:10-23

PubMed: 29080813 ( click the link to review the publication )

Int J Obes , 2018, 42(2):252-259

PubMed: 28925407 ( click the link to review the publication )

J Cell Sci, 2018, 131(10)

PubMed: 29678906 ( click the link to review the publication )

Am J Physiol Lung Cell Mol Physiol, 2018, 314(5):L882-L892

PubMed: 29345196 ( click the link to review the publication )

Front Endocrinol (Lausanne), 2018, 9:424

PubMed: 30140255 ( click the link to review the publication )
Int J Oncol, 2018,

PubMed: 30015925 ( click the link to review the publication )

Mol Immunol, 2018, 101:221-228

PubMed: 30007232 ( click the link to review the publication )

Molecules, 2018, 23(6)E1478

PubMed: 29921758 ( click the link to review the publication )

Blood, 2017, 129(14):1969-1979

PubMed: 28151428 ( click the link to review the publication )

Proc Natl Acad Sci U S A, 2017, 114(11):2934-2939

PubMed: 28246332 ( click the link to review the publication )

Proc Natl Acad Sci U S A, 2017, 114(7):1643-1648

PubMed: 28130546 ( click the link to review the publication )

Elife, 2017, 6

PubMed: 28199182 ( click the link to review the publication )

Oxid Med Cell Longev, 2017, 2017:7601592

PubMed: 29147463 ( click the link to review the publication )

Mol Cancer Res, 2017, 15(7):852-861

PubMed: 28314843 ( click the link to review the publication )

Sci Rep, 2017,

PubMed: 29259270 ( click the link to review the publication )

Endocrinology, 2017, 158(7):2255-2268

PubMed: 28444169 ( click the link to review the publication )

Oncotarget, 2017, 8(53):91516-91529

PubMed: 29207662 ( click the link to review the publication )

Oncotarget, 2017, 8(65):109319-109331

PubMed: 29312610 ( click the link to review the publication )

J Clin Invest, 2016, 126(4):1300-10

PubMed: 26927669 ( click the link to review the publication )

Nat Commun, 2016, 7:12428

PubMed: 27687249 ( click the link to review the publication )

Small, 2016, 12(24):3270-82

PubMed: 27167493 ( click the link to review the publication )

Neuro Oncol, 2016, 10.1093/neuonc/now139

PubMed: 27402815 ( click the link to review the publication )

PLoS Genet, 2016, 12(9):e1006279

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

Biochim Biophys Acta, 2016, 1863(11):2758-2765

PubMed: 27566291 ( click the link to review the publication )

Photodiagnosis Photodyn Ther, 2016, 14:119-27

PubMed: 26607555 ( click the link to review the publication )

Hum Mol Genet, 2016, 25(1):9-23

PubMed: 26494904 ( click the link to review the publication )

Nat Cell Biol, 2015, 17(1):57-67

PubMed: 25487280 ( click the link to review the publication )

Cell Rep, 2015, 10.1016/j.celrep.2015.04.049

PubMed: 26027934 ( click the link to review the publication )

Sci Rep, 2015, 5:13414

PubMed: 26299368 ( click the link to review the publication )
Mol Pharmacol, 2015, 87(4):572-81

PubMed: 25583084 ( click the link to review the publication )

Mol Pharmacol, 2015, 87(4):572-81

PubMed: ( click the link to review the publication )

Biochem Biophys Res Commun, 2015, 458(4):908-12

PubMed: 25704089 ( click the link to review the publication )

Biochem Biophys Res Commun, 2015, 458(4):908-12

PubMed: ( click the link to review the publication )

Oncotarget, 2015, 8(48):83457-83468

PubMed: 29137356 ( click the link to review the publication )

Oncotarget, 2015, 6(29):28401-24

PubMed: 26315114 ( click the link to review the publication )

Blood, 2014, 123(10):1516-24

PubMed: 24408322 ( click the link to review the publication )

Autophagy, 2014, 10(7):1212-28

PubMed: 24813621 ( click the link to review the publication )

J Med Chem, 2014, 57(15):6342-53

PubMed: 24978112 ( click the link to review the publication )

Oncol Rep, 2014, 32(5):1991-8

PubMed: 25216185 ( click the link to review the publication )

PLoS One, 2014, 9(10):e109799

PubMed: 25289677 ( click the link to review the publication )

PLoS One, 2014, 9(11):e112014

PubMed: 25390891 ( click the link to review the publication )

Proc Natl Acad Sci U S A, 2013, 110(42):16975-80

PubMed: 24082147 ( click the link to review the publication )

Cancer Lett, 2013, 341(2):224-30

PubMed: 23941832 ( click the link to review the publication )

Endocrinology, 2013, 154(9):3219-27

PubMed: 23782942 ( click the link to review the publication )

Asian Pac J Cancer Prev, 2013, 14(8):4823-7

PubMed: 24083752 ( click the link to review the publication )

Leukemia, 2012, 26(4):708-15

PubMed: 21926964 ( click the link to review the publication )

Mol Cell Proteomics, 2012, 11(6):M112.017764

PubMed: 22345495 ( click the link to review the publication )

Purity & Quality Control

Choose Selective JAK Inhibitors

Biological Activity

Description

AZD1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of 0.26 nM in a cell-free assay, selectivity against JAK3 and Tyk2, and to a smaller extent against JAK1. Phase 1.

Targets

JAK2 ^[1]
(Cell-free assay)

0.26 nM

In vitro

5μM AZD1480 induces G2/M arrest and cell death by inhibiting Aurora kinases. ^[1] AZD1480 is a potent JAK2 inhibitor that can suppress growth, survival, as well as FGFR3 and STAT3 signaling and downstream targets including Cyclin D2 in human multiple myeloma cells. At low micromolar concentrations, AZD1480 blocks cell proliferation and induces apoptosis of myeloma cell lines. ^[2]AZD1480 effectively blocks constitutive and stimulus-induced JAK1, JAK2, and STAT-3 phosphorylation in both human and murine glioma cells, and leads to a decrease in cell proliferation and induction of apoptosis. ^[3]AZD1480 is a potent, competitive small-molecule inhibitor of JAK1/2 kinase, and that it is capable of inhibiting STAT3 phosphorylation and tumor growth in a STAT3-dependent manner. AZD1480 inhibits tumor angiogenesis and metastasis in part by affecting the tumor microenvironment. ^[4]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
SW620	NHS3RWJHfW6ldHnvckBCe3OjeR?=	NX;EdmFoPSEQvF2=	M13MPFQ5KGh?	NILP[WVFVVOR	MofWZoxw[2u\|IFrBT\|IwW1SDVEOgd4lodmGuaX7n	M2KwXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OUW0PVc1Lz5{NUm1OFk4PDxxYU6=
LoVo	NGHoN45HfW6ldHnvckBCe3OjeR?=	M2W4cVUh\|ryP	Mn;ZOFghcA>?	M4LsXmROW09?	NIPsU29jdG:la4OgTmFMOi:VVFHUN{B{cWewYXzpcoc>	NGP3S5I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUm1OFk4PCd-MkW5OVQ6PzR:L3G+
HN5	MWHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		NF3E[og4OiCq		M{ThRWVEPTB;Mz64NUDDuSBzLkm5JO69VQ>?	NGTZNIk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUixNFAyOCd-MkW4NVAxOTB:L3G+
Cal33	MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		M4r0elczKGh?		NH;RWWpGSzVyPUOuN\|chyrFiMD63OUDPxE1?	MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPThzMECxNEc,OjV6MUCwNVA9N2F-
UM-22B	NYfYeJQzT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		MUC3NkBp		NIXaPJlGSzVyPUKuOlYhyrFiMD6yOEDPxE1?	NHzObnk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUixNFAyOCd-MkW4NVAxOTB:L3G+
686LN	M3nVVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		NHzCeHM4OiCq		MVzFR\|UxRTJwMEWgxtEhOS5\|MzFOwG0>	NVPr[mhORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NVAxOTBpPkK1PFExODFyPD;hQi=>
UM SCC-1	MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		MV23NkBp		NVfVWo8zTUN3ME2xMlY4KMLzIECuOFIh\|ryP	NFHF[WE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUixNFAyOCd-MkW4NVAxOTB:L3G+
UM-22A	MmTaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		NUTJeo1OPzJiaB?=		NX3RNIE{TUN3ME2xMlMzKMLzIECuN\|kh\|ryP	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPThzMECxNEc,OjV6MUCwNVA9N2F-
OSC19	M2PNNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		Ml\HO\|IhcA>?		NVLGdWY2TUN3ME2xMlI3KMLzIECuNlAh\|ryP	Mlu3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6MUCwNVAoRjJ3OEGwNFExRC:jPh?=
PCI-52	MnjQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		MVK3NkBp		MUjFR\|UxRTFwMECgxtEhOC5yOTFOwG0>	NYS4dmtJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NVAxOTBpPkK1PFExODFyPD;hQi=>
PCI-15B	MmLOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		NXrOUoxRPzJiaB?=		NX3ZbWdUTUN3ME2wMlk6KMLzIEGuO\|Qh\|ryP	NUTKN3J1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NVAxOTBpPkK1PFExODFyPD;hQi=>
UMSCC-1	MV7GeY5kfGmxbjDBd5NigQ>?	NGHoZWoxNjByMEWtNU43KM7:TR?=	MlrkNlQhcA>?		NGLsRXpi[nKxZ3H0[ZMhUUxvNvMAl4lv\HWlZXSgeZAuemWpdXzheIlwdiCxZjDwV3RCXDOWeYK3NFXDqGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz	Mn3RQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6MUCwNVAoRjJ3OEGwNFExRC:jPh?=
Cal33	MX\GeY5kfGmxbjDBd5NigQ>?	MUKwMlAxODVvMz64JO69VQ>?	MlnyNlQhcA>?		Mmj2ZYJzd2ejdHXzJGlNNTckgKPpcoR2[2WmIIXwMZJm\3WuYYTpc44hd2ZicGPURXQ{XHm{N{C1xsBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>	MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPThzMECxNEc,OjV6MUCwNVA9N2F-
HH5	MXPGeY5kfGmxbjDBd5NigQ>?	MoK1NE4xODB3LUOuPEDPxE1?	M{DGeFI1KGh?		M4jBSYFjem:pYYTld{BKVC144pETbY5lfWOnZDD1dE1z\We3bHH0bY9vKG:oIIDTWGFVO1S7ckewOeKhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>	MljhQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6MUCwNVAoRjJ3OEGwNFExRC:jPh?=
UM-22A	MUHGeY5kfGmxbjDBd5NigQ>?	MYGwMlAxODVvMT62JO69VQ>?	NEDDXIMzPCCq		NHOzU4hi[nKxZ3H0[ZMhUUxvNvMAl4lv\HWlZXSgeZAuemWpdXzheIlwdiCxZjDwV3RCXDOWeYK3NFXDqGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz	NX7m[np{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NVAxOTBpPkK1PFExODFyPD;hQi=>
A1847	NFnCdY9HfW6ldHnvckBCe3OjeR?=	NHfmWXAxNjB3LUGwJO69VQ>?	M2nKOlI1KGh?	NXW1SZBnTE2VT9Mg	NGDkc5Bz\WS3Y3XzJJBpd3OyaH;yfYxifGWmIGPURXQ{KGyndnXsdy=>	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ2NkCxOUc,OjV4NE[wNVU9N2F-
OVCAR-5	M2LMe2Z2dmO2aX;uJGF{e2G7	NWDLNXhTOC5yNT2xNEDPxE1?	NIXm[4EzPCCq	M3rTdGROW00EoB?=	M2PDTJJm\HWlZYOgdIhwe3Cqb4L5cIF1\WRiU2TBWFMhdGW4ZXzz	MnjxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV4NE[wNVUoRjJ3NkS2NFE2RC:jPh?=
OVCAR-8	NEHGb3FHfW6ldHnvckBCe3OjeR?=	M{jwXlAvODVvMUCg{txO	M3:zNVI1KGh?	NYn5[Gd2TE2VT9Mg	M3fjbJJm\HWlZYOgdIhwe3Cqb4L5cIF1\WRiU2TBWFMhdGW4ZXzz	MkPDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV4NE[wNVUoRjJ3NkS2NFE2RC:jPh?=
MOVCAR-5447	M{fSdGZ2dmO2aX;uJGF{e2G7	MkH1NE4xPS1zMDFOwG0>	NX\YeWpsOjRiaB?=	MoDtSG1UV8Li	MXry[YR2[2W\|IIDoc5NxcG:{eXzheIVlKFOWQWSzJIxmfmWucx?=	MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ2NkCxOUc,OjV4NE[wNVU9N2F-
MOVCAR-5009	MV\GeY5kfGmxbjDBd5NigQ>?	MWOwMlA2NTFyIN88US=>	NEXqbnYzPCCq	NHHkWWJFVVORwrC=	M1v5XJJm\HWlZYOgdIhwe3Cqb4L5cIF1\WRiU2TBWFMhdGW4ZXzz	M3fTc\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkS2NFE2Lz5{NU[0OlAyPTxxYU6=
A1847	NHvaS5NE\WyuIG\pZYJqdGm2eTDBd5NigQ>?	MkXHNE4xPS1zMDFOwG0>	NXric4N2PzJiaB?=	Mlz0SG1UVw>?	MnKzdoVlfWOnczDj[YxtKH[rYXLpcIl1gSCjdDD0bIUh[2:wY3XycpRz[XSrb36gc4YhPSEQvF2=	M1;uXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkS2NFE2Lz5{NU[0OlAyPTxxYU6=
OVCAR-5	NHH2WVRE\WyuIG\pZYJqdGm2eTDBd5NigQ>?	NVPKd3dLOC5yNT2xNEDPxE1?	Mnn2O\|IhcA>?	M1TLNGROW09?	NVPRRnl4emWmdXPld{Bk\WyuII\pZYJqdGm2eTDheEB1cGViY3;uZ4VzdnS{YYTpc44hd2ZiNTFOwG0>	MnjwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV4NE[wNVUoRjJ3NkS2NFE2RC:jPh?=
OVCAR-8	NHTTWJFE\WyuIG\pZYJqdGm2eTDBd5NigQ>?	Mo\INE4xPS1zMDFOwG0>	NXfVZmxLPzJiaB?=	NY[3OGllTE2VTx?=	MYLy[YR2[2W\|IHPlcIwhfmmjYnnsbZR6KGG2IITo[UBkd26lZYLueJJifGmxbjDv[kA2KM7:TR?=	NFTreJU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[0OlAyPSd-MkW2OFYxOTV:L3G+
OVCAR-5	M13Le2Fxd3C2b4Ppd{BCe3OjeR?=	NUTLXWxyOC53L{GvOUDPxE1?	M2T1UFQ5KGh?	MXLEUXNQ	MlfNbY5lfWOnczDzbYdvcW[rY3HueEBieG:ydH;zbZMh[XRiaHnnbEBkd26lZYLueJJifGmxbh?=	M1XpdFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkS2NFE2Lz5{NU[0OlAyPTxxYU6=
OVCAR-8	NWG4OWhzSXCxcITvd4l{KEG\|c3H5	M4DxcFAvPS9zL{Wg{txO	NVnqWnJbPDhiaB?=	M3S4VWROW09?	M3rnN4lv\HWlZYOgd4lodmmoaXPhcpQh[XCxcITvd4l{KGG2IHjp[4gh[2:wY3XycpRz[XSrb36=	MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ2NkCxOUc,OjV4NE[wNVU9N2F-
AKRSL	M3vteGNmdGxiVnnhZoltcXS7IFHzd4F6		M4ntclczKGh?		M1HDXGlEPTExvK6xNEDPxE1?	MnjKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV3MES2N\|UoRjJ3NUC0OlM2RC:jPh?=
PALJDL	NUX1VW0{S2WubDDWbYFjcWyrdImgRZN{[Xl?		NUmxXHh{PzJiaB?=		Mnv0TWM2OD1{LkSg{txO	NYXIdm9iRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW1NFQ3OzVpPkK1OVA1PjN3PD;hQi=>
MO4	M1;BUGZ2dmO2aX;uJGF{e2G7	MWOwMlUwOS93IN88US=>	M3m4U\|YhcA>?		MYLpcohq[mm2czDQMXNVSVR\|IHX4dJJme3Orb39CpC=>	M4jnTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MUS5OVM2Lz5{NUG0PVU{PTxxYU6=
DU145	MUfGeY5kfGmxbjDBd5NigQ>?	MlvHNE0zODBibl2=	M3nae\|EhcMLi		MWLzeZBxemW\|c3XzJGlNNTZvYXP0bZZifGWmIGP0ZZQ{KGGwZDDFVmsyNzJic3nncoFtcW6p	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDV5N{m0Nkc,OjR3N{e5OFI9N2F-
DU145	M4jZZ2Z2dmO2aX;uJGF{e2G7	MmLHPFAxKG6P	NYXYbVl{PzJiaB?=		MV7zeZBxemW\|c3XzJGlNNTZvaX7keYNm\CCvaXfyZZRwenl?	NXvZeGY6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS1O\|c6PDJpPkK0OVc4QTR{PD;hQi=>
CWR22Rv1	MmTLSpVv[3Srb36gRZN{[Xl?	MkDpPFAxKG6P	MYi3NkBp		MlTud5VxeHKnc4Pld{BKVC14LXnu[JVk\WRibXnndoF1d3K7	MojXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR3N{e5OFIoRjJ2NUe3PVQzRC:jPh?=
N592	NFmzO4RIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=				MXHJR\|UxRTBwOESg{txO	MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF3OEewNUc,OjRzNUi3NFE9N2F-
H82	MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?				MmfKTWM2OD1zLkO3JO69VQ>?	MWG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF3OEewNUc,OjRzNUi3NFE9N2F-
GLC4	Mly4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				MmTCTWM2OD1zLke5JO69VQ>?	Ml7xQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzNUi3NFEoRjJ2MUW4O\|AyRC:jPh?=
H526	MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?				NIjIbJhKSzVyPUOuNFgh\|ryP	MYC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF3OEewNUc,OjRzNUi3NFE9N2F-
H1173	M4DJZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7				M4LCeGlEPTB;Mj6zPUDPxE1?	M1HENlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MUW4O\|AyLz5{NEG1PFcxOTxxYU6=
DMS114	M2\5UWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7				MX3JR\|UxRTBwN{Og{txO	NHf2b5Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEG1PFcxOSd-MkSxOVg4ODF:L3G+
NCI-N592	NH\SXXNHfW6ldHnvckBCe3OjeR?=	NVHvPGtZOC5\|L{GvN{DPxE1?	NGHkZoIzPCCq		MmnCbY5lfWOnczDHNk9OKGOnbHygZ5lkdGViYYLy[ZN1	M2XTWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MUW4O\|AyLz5{NEG1PFcxOTxxYU6=
GLC4	MlfmSpVv[3Srb36gRZN{[Xl?	MnHnNE4{NzFxMzFOwG0>	Ml\UNlQhcA>?		NWDNV4U3cW6mdXPld{BIOi:PIHPlcIwh[3mlbHWgZZJz\XO2	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF3OEewNUc,OjRzNUi3NFE9N2F-
NCI-H82	NF3CRYlHfW6ldHnvckBCe3OjeR?=	NWHwepVUOC5\|L{GvN{DPxE1?	MV2yOEBp		NIrNWW1qdmS3Y3XzJGczN01iY3XscEBkgWOuZTDhdpJme3R?	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF3OEewNUc,OjRzNUi3NFE9N2F-
NCI-N592	MVzBdI9xfG:\|aYOgRZN{[Xl?	MXmwMlMwOS9\|IN88US=>	NVy2XWZGPDhiaB?=		M1LjV4lv[3KnYYPld{B1cGVibHX2[Ywhd2ZiY3zlZZZm\C2FYYPwZZNmKDN?	M1rmSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MUW4O\|AyLz5{NEG1PFcxOTxxYU6=
GLC4	NHraOHFCeG:ydH;zbZMhSXO\|YYm=	M{PUflAvOy9zL{Og{txO	M4jwNlQ5KGh?		NF;vZYJqdmO{ZXHz[ZMhfGinIHzleoVtKG:oIHPs[YF3\WRvQ3HzdIF{\SB\|	MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF3OEewNUc,OjRzNUi3NFE9N2F-
NCI-H82	NVnSSpJLSXCxcITvd4l{KEG\|c3H5	M1XPUVAvOy9zL{Og{txO	MkG1OFghcA>?		Mmn3bY5kemWjc3XzJJRp\SCuZY\lcEBw\iClbHXheoVlNUOjc4Dhd4UhOw>?	MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF3OEewNUc,OjRzNUi3NFE9N2F-
CWR22Rv1	NEfEUGpCeG:ydH;zbZMhSXO\|YYm=				MXTJR\|UxRTBwNEiyJO69VQ>?	NEHPW\|Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{m0NlA6PSd-MkO5OFIxQTV:L3G+
CWR22Pc	M1vwTmFxd3C2b4Ppd{BCe3OjeR?=				MonXTWM2OD1yLkSzPEDPxE1?	MmTtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7NEKwPVUoRjJ\|OUSyNFk2RC:jPh?=
PC-3	Mkf3RZBweHSxc3nzJGF{e2G7				NH7MSodKSzVyPUGuO\|U2KM7:TR?=	MnjIQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7NEKwPVUoRjJ\|OUSyNFk2RC:jPh?=
DU145	NVT1UHRtSXCxcITvd4l{KEG\|c3H5				Mkj3TWM2OD1\|LkWxO{DPxE1?	NHjiVmI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{m0NlA6PSd-MkO5OFIxQTV:L3G+
RC165N	NWnzNGs3SXCxcITvd4l{KEG\|c3H5				M{\ie2lEPTB;Mj6wPFMh\|ryP	NXezfJBnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5OFIxQTVpPkKzPVQzODl3PD;hQi=>
ARPE19	Mn76S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			Mmr4SG1UVw>?	NHn1fHFKSzVyPUK0MlM5KM7:TR?=	MmHnQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ\|NUOxPVIyRC:jPh?=
HEK293	MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MV7EUXNQ	MXPJR\|UxRThwNkeg{txO	NW\DemFzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
KCNR	NEn0eW9Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MnfsSG1UVw>?	NEDZbJRKSzVyPUCuOFYh\|ryP	MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
SY5Y	NYjJbFhGT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			MY\EUXNQ	NEHxPINKSzVyPUCuN\|Yh\|ryP	MmjYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ\|NUOxPVIyRC:jPh?=
BE2	NXvIOJl6T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NV\iWmE6TE2VTx?=	MmTFTWM2OD1yLkexJO69VQ>?	MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
AS	MleyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NGGwO\|VFVVOR	NV\qZZBrUUN3ME2xMlU{KM7:TR?=	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
NGP	NUjpS456T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NUTx[Gs6TE2VTx?=	NH;aWnNKSzVyPUCuOVYh\|ryP	MWC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
IMR32	M1LyNWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NV;Z[JVTTE2VTx?=	NFPlR5hKSzVyPUCuOlYh\|ryP	M4C4OFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NUOxPVIyLz5{M{WzNVkzOTxxYU6=
LAN5	M1;B[mdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MWfEUXNQ	M2XV[2lEPTB;MT6wOEDPxE1?	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
RH18	Mn3uS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MnjESG1UVw>?	M1Swb2lEPTB;MT60NkDPxE1?	MnPGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ\|NUOxPVIyRC:jPh?=
RH30	MnjJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NWXXc2tCTE2VTx?=	Mlf4TWM2OD1zLkK1JO69VQ>?	MlnLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ\|NUOxPVIyRC:jPh?=
RH17	M1nzO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NIjlZpZFVVOR	MmCxTWM2OD1{LkWxJO69VQ>?	NYC0W4NIRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
RH28	NYnB[lNST3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NXHITFQyTE2VTx?=	NH2wWoZKSzVyPUSuNlgh\|ryP	Mn7PQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ\|NUOxPVIyRC:jPh?=
RH36	M4fpbmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NH;QOG9FVVOR	NHnkTZRKSzVyPUWuN\|ch\|ryP	NUDjTHlFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
RH41	MnzkS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NIXR[2xFVVOR	NYfW[I1XUUN3ME2wMlQ5KM7:TR?=	NVTMXG5xRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
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TC32	MnvyS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NUKxNWk4TE2VTx?=	NF74R5pKSzVyPUOuPFUh\|ryP	Mn\BQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ\|NUOxPVIyRC:jPh?=
TC71	NUDhboJHT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			M3jGXmROW09?	MoTnTWM2OD12LkOzJO69VQ>?	NIX1SFU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N\|E6OjF:L3G+
KCNR	NXrxRZN7SXCxcITvd4l{KEG\|c3H5	NWTnSFJDOC53L{GuNE8zNjVizszN	NF7tR2QzPCCq	MX7EUXNQ	NIi5WndqdmS3Y3XzJIFvKGmwY4LlZZNmKGmwIHPhd5Bie2ViMz:3JIFkfGm4aYT5	NWXpSGNkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
SY5Y	M{LlcWFxd3C2b4Ppd{BCe3OjeR?=	NH\ZWJUxNjVxMT6wM\|IvPSEQvF2=	MXKyOEBp	MX3EUXNQ	NUPBW5M3cW6mdXPld{BidiCrbnPy[YF{\SCrbjDjZZNx[XOnIEOvO{Bi[3Srdnn0fS=>	MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
Rh18	M{KyTGFxd3C2b4Ppd{BCe3OjeR?=	MXqwMlUwOS5yL{KuOUDPxE1?	NVvEPZNLOjRiaB?=	Mk\oSG1UVw>?	MlfzbY5lfWOnczDhckBqdmO{ZXHz[UBqdiClYYPwZZNmKDNxNzDhZ5Rqfmm2eR?=	MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
TC32	M2W1NWFxd3C2b4Ppd{BCe3OjeR?=	MoL5NE42NzFwMD:yMlUh\|ryP	MXmyOEBp	M4ewUGROW09?	M37qWolv\HWlZYOgZY4hcW6lcnXhd4UhcW5iY3HzdIF{\SB\|L{egZYN1cX[rdIm=	NVTJbZpNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
KCNR	MWrGeY5kfGmxbjDBd5NigQ>?	NITs[JkxNjVxMT6wM\|IvPS93IN88US=>	NG\LNWszPCCq	MXXEUXNQ	M1XKPYlvcGmkaYTzJIJwfGhiZX7kc4dmdm:3czDjc45{fGm2dYTpeoUh[W6mIFnMMVYucW6mdXPl[EBUXEGWMzDhZ5RqfmG2aX;u	MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
SY5Y	NXzWc29FTnWwY4Tpc44hSXO\|YYm=	NFf5[oMxNjVxMT6wM\|IvPS93IN88US=>	MnGxNlQhcA>?	MVnEUXNQ	Mn;sbY5pcWKrdIOgZo91cCCnbnTv[4Vvd3W\|IHPvcpN1cXS3dHn2[UBidmRiSVytOk1qdmS3Y3XkJHNVSVR\|IHHjeIl3[XSrb36=	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
Rh18	M{WyemZ2dmO2aX;uJGF{e2G7	NYTFXGVZOC53L{GuNE8zNjVxNTFOwG0>	MmWyNlQhcA>?	M1[5OWROW09?	NXHadYROcW6qaXLpeJMh[m:2aDDlcoRw\2Wwb4XzJINwdnO2aYT1eIl3\SCjbnSgTWwuPi2rbnT1Z4VlKFOWQWSzJIFkfGm4YYTpc44>	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
TC32	Ml\wSpVv[3Srb36gRZN{[Xl?	NGXsdnUxNjVxMT6wM\|IvPS93IN88US=>	NWDWWJF2OjRiaB?=	NX24VmMyTE2VTx?=	NVXQbpNvcW6qaXLpeJMh[m:2aDDlcoRw\2Wwb4XzJINwdnO2aYT1eIl3\SCjbnSgTWwuPi2rbnT1Z4VlKFOWQWSzJIFkfGm4YYTpc44>	NEDQS\|c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N\|E6OjF:L3G+
TPC-1	NVLS[mRDT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NGGyTWwyKML3TR?=	M4\3NVAuPCCm	NEXWOVFFVVOR	M1PLcYlvcGmkaYTzJINmdGxiZ4Lve5RpKGGodHXyJFIh\CC2cnXheI1mdnR?	NFzScZg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{C1OlQ6QSd-MkOwOVY1QTl:L3G+
MZ-CRC1	M{flc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	NXLYPJQ6OSEEtV2=	NF32WFUxNTViZB?=	NXrpeopNTE2VTx?=	M1fLNolvcGmkaYTzJINmdGxiZ4Lve5RpKGGodHXyJFEh\CC2cnXheI1mdnR?	NFXaV5c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{C1OlQ6QSd-MkOwOVY1QTl:L3G+
TT	MWjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	Mk\5NUDDvU1?	NXSyfIlbOC12IHS=	NYrifFljTE2VTx?=	MYDpcohq[mm2czDj[YxtKGe{b4f0bEBi\nSncjCxJIQhfHKnYYTt[Y51	NVHsdpViRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOwOVY1QTlpPkKzNFU3PDl7PD;hQi=>
TPC-1	NGDC[npHfW6ldHnvckBCe3OjeR?=	MV[xJOK2VQ>?	M{e1T\|czKGh?	NWfjN\|JvTE2VTx?=	MkLVbY5lfWOnczDHNUBjdG:la3Hn[S=>	Mn;xQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjNyNU[0PVkoRjJ\|MEW2OFk6RC:jPh?=
MZ-CRC1	MV7GeY5kfGmxbjDBd5NigQ>?	NXfvbnRLOSEEtV2=	MoTuO\|IhcA>?	MljCSG1UVw>?	MnrBbY5lfWOnczDHNUBjdG:la3Hn[S=>	MmTQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjNyNU[0PVkoRjJ\|MEW2OFk6RC:jPh?=
TT	M3jRSWZ2dmO2aX;uJGF{e2G7	NEiye40yKML3TR?=	NYPjSJMyPzJiaB?=	MXjEUXNQ	NUTHTWpDcW6mdXPld{BIOSCkbH;jb4Fo\Q>?	NHfPVYU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{C1OlQ6QSd-MkOwOVY1QTl:L3G+
MZ-CRC1	NILQdFlCeG:ydH;zbZMhSXO\|YYm=	MkTYNUDDvU1?	MUO0PEBp	MlP5SG1UVw>?	M1:4d4lv\HWlZYOgZZBweHSxc3nz	M2fvTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|MEW2OFk6Lz5{M{C1OlQ6QTxxYU6=
TT	NWCzdoY3SXCxcITvd4l{KEG\|c3H5	M2jsO\|EhyrWP	MoLYOFghcA>?	M1HINWROW09?	NUT0bZBDcW6mdXPld{BieG:ydH;zbZM>	NVjTNpI1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOwOVY1QTlpPkKzNFU3PDl7PD;hQi=>
HD-LM2	NWDvUolvT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		MX63NwKBkWh?	NGC0OXJFVVOR	NHSxNolKSzVyPUeuPFQ1KM7:TR?=	M4HyNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OEK5NFk1Lz5{MkiyPVA6PDxxYU6=
L-428	MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		MV:3NwKBkWh?	MXzEUXNQ	NYXzbIpXUUN3ME23Mlk1PyEQvF2=	NEnHTpQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkiyPVA6PCd-MkK4NlkxQTR:L3G+
KM-H2	NGfE[2pIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		MYG3NwKBkWh?	NXXmbHB6TE2VTx?=	MkTlTWM2OD1zLkOwPEDPxE1?	NGPEUZA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkiyPVA6PCd-MkK4NlkxQTR:L3G+
L-540	MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		MWW3NwKBkWh?	MX;EUXNQ	NEDQeFNKSzVyPUiuNlE3KM7:TR?=	NG\ubnQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkiyPVA6PCd-MkK4NlkxQTR:L3G+
HD-LM2	MULGeY5kfGmxbjDBd5NigQ>?	MWqwMlEwOC53L{GvOUDPxE1?	MXS3NwKBkWh?	NHzHV3JFVVOR	MkfkbY5pcWKrdIOgV3RCXDNuIGPURXQ2KGGwZDDTWGFVPiCyaH;zdIhwenmuYYTpc44>	MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjh{OUC5OEc,OjJ6MkmwPVQ9N2F-
L-428	NHP3VmdHfW6ldHnvckBCe3OjeR?=	M3PlPFAvOS9yLkWvNU82KM7:TR?=	MnvrO\|LjiImq	NYW1VIJETE2VTx?=	M{nUOolvcGmkaYTzJHNVSVR\|LDDTWGFVPSCjbnSgV3RCXDZicHjvd5Bpd3K7bHH0bY9v	NE[5ZlE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkiyPVA6PCd-MkK4NlkxQTR:L3G+
KM-H2	MV\GeY5kfGmxbjDBd5NigQ>?	NWH4PYc3OC5zL{CuOU8yNzVizszN	NEfTfJM4OuLCiXi=	MX\EUXNQ	Mnu0bY5pcWKrdIOgV3RCXDNuIGPURXQ2KGGwZDDTWGFVPiCyaH;zdIhwenmuYYTpc44>	M2fvUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OEK5NFk1Lz5{MkiyPVA6PDxxYU6=
L-540	MYPGeY5kfGmxbjDBd5NigQ>?	MkTjNE4yNzBwNT:xM\|Uh\|ryP	NEjVN484OuLCiXi=	M3XPSWROW09?	NUPYfZBvcW6qaXLpeJMhW1SDVEOsJHNVSVR3IHHu[EBUXEGWNjDwbI9{eGixconsZZRqd25?	MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjh{OUC5OEc,OjJ6MkmwPVQ9N2F-
HD-LM2	NHLRXoRCeG:ydH;zbZMhSXO\|YYm=	MUexM\|Uh\|ryP	M1rMRVcz6oDLaB?=	MkTpSG1UVw>?	NYX3XlFtcW6mdXPld{BieG:ydH;zbZM>	M2XWUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OEK5NFk1Lz5{MkiyPVA6PDxxYU6=
L-428	NWrHXFdpSXCxcITvd4l{KEG\|c3H5	MnHQNU82KM7:TR?=	M3vvUFcz6oDLaB?=	MlX1SG1UVw>?	NUjBTVZWcW6mdXPld{BieG:ydH;zbZM>	M3LhPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OEK5NFk1Lz5{MkiyPVA6PDxxYU6=
KM-H2	MnLlRZBweHSxc3nzJGF{e2G7	MnzNNU82KM7:TR?=	NWHjcHZvPzMkgJno	MVzEUXNQ	M2jtbolv\HWlZYOgZZBweHSxc3nz	MWW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjh{OUC5OEc,OjJ6MkmwPVQ9N2F-
L-540	NUP0NI1GSXCxcITvd4l{KEG\|c3H5	MljaNU82KM7:TR?=	NUnjSGF4PzMkgJno	Mn25SG1UVw>?	NHvPR4RqdmS3Y3XzJIFxd3C2b4Ppdy=>	MoDxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ6MkmwPVQoRjJ{OEK5NFk1RC:jPh?=
U251-MG	NV6zZ3BxTnWwY4Tpc44hSXO\|YYm=	MWKxJOK2VQ>?	NX21V\|FYOC1zNjDo		NIHlXoFqdmirYnn0d{Bkd26\|dHn0eZRqfmViU2TBWE0{KGGwZDDKRWszKGGldHn2ZZRqd25?	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjB{N{[5NUc,OjJyMke2PVE9N2F-
U87-MG	NVm5SWNiTnWwY4Tpc44hSXO\|YYm=	MWqxJOK2VQ>?	M{\uXlAuOTZiaB?=		MXvpcohq[mm2czDjc45{fGm2dYTpeoUhW1SDVD2zJIFv\CCMQVuyJIFkfGm4YYTpc44>	MnfkQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJyMke2PVEoRjJ{MEK3OlkyRC:jPh?=
4C8	MVXGeY5kfGmxbjDBd5NigQ>?	M3XSd\|EhyrWP	NVzxS2ZMOC1zNjDo		NV\OOVZJcW6qaXLpeJMh[2:wc4TpeJV1cX[nIGPURXQuOyCjbnSgTmFMOiCjY4TpeoF1cW:w	NXXKTWFXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKwNlc3QTFpPkKyNFI4PjlzPD;hQi=>
U251-MG	MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M1:xXVEwOTBiwsXN	MkLhNlQwPDhxN{KgbC=>		MXnpcohq[mm2czDj[YxtKHC{b3zp[oVz[XSrb36gZZQh[SClb37j[Y51emG2aX;uJI9nKDFyINM1US=>	M1PuW\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MEK3OlkyLz5{MkCyO\|Y6OTxxYU6=
U87-MG	NGjxfmxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	NHX5VVEyNzFyINM1US=>	NYC3N3pbOjRxNEivO\|IhcA>?		NHPveJhqdmirYnn0d{Bk\WyuIIDyc4xq\mW{YYTpc44h[XRiYTDjc45k\W62cnH0bY9vKG:oIEGwJOK2VQ>?	MkLYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJyMke2PVEoRjJ{MEK3OlkyRC:jPh?=
4C8	NGTmSHFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MY[xM\|ExKML3TR?=	NVjNdJNiOjRxNEivO\|IhcA>?		M{[zc4lvcGmkaYTzJINmdGxicILvcIln\XKjdHnvckBifCCjIHPvcoNmdnS{YYTpc44hd2ZiMUCgxtVO	M1XyelxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MEK3OlkyLz5{MkCyO\|Y6OTxxYU6=
U266	NGjKR5NCeG:ydH;zbZMhSXO\|YYm=	M{XLbFAvPS1{IN88US=>	MmLNOFgwPzJiaB?=		MljNbY5lfWOnczDhdI9xfG:\|aYOg[I9{\SCmZYDlcoRmdnSueR?=	NYD6dGp1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxOlQ2OTdpPkKxNVY1PTF5PD;hQi=>
Kms.11	MUDBdI9xfG:\|aYOgRZN{[Xl?	NV\rRXdYOC53LUKg{txO	NH[2Vos1QC95MjDo		NFnFXnpqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5	NYjydmViRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxOlQ2OTdpPkKxNVY1PTF5PD;hQi=>
8226	MWnBdI9xfG:\|aYOgRZN{[Xl?	MW[wMlUuOiEQvF2=	Mm\mOFgwPzJiaB?=		M3Sx[Ylv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm=	NHTG[GY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUG2OFUyPyd-MkGxOlQ2OTd:L3G+
SET2	M3PJb2dzd3e2aDDpcohq[mm2aX;uJIF{e2G7		MYS0PEBpenN?		M1TuXWdzd3e2aDDpcohq[mm2aX;uJI9nKGi3bXHuJHNGXDJiY3XscJMh\XiycnXzd4lv\yCMYXuyJHY3OTeIIH31eIFvfCCjZoTldkA1QCCqcoOgZpkhVVSVIHHzd4F6NCCJSUWwJF0hOC5yMU[g{txONg>?	MkPqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzM{iyOFYoRjJzMUO4NlQ3RC:jPh?=
SET2	MmXUSpVv[3Srb36gZZN{[Xl?		NVvlOJpROSCqch?=		MlrqTY5pcWKrdHnvckBw\iCVdHH0N{BxcG:\|cHjvdplt[XSrb36gbY4hcHWvYX6gV2VVOiClZXzsd{Bi\nSncjCxJIhzKGK7IGfld5Rmem5iYnzveJRqdmduIFnDOVAhRSByLkCyN{DPxE1w	M{fkTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
SET2	NWLUVFlDTnWwY4Tpc44h[XO\|YYm=		MlvBNUBpeg>?		Ml7yTY5pcWKrdHnvckBw\iCVdHH0OUBxcG:\|cHjvdplt[XSrb36gbY4hcHWvYX6gV2VVOiClZXzsd{Bi\nSncjCxJIhzKGK7IGfld5Rmem5iYnzveJRqdmduIFnDOVAhRSByLkCyOUDPxE1w	NHT4TJo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUGzPFI1Pid-MkGxN\|gzPDZ:L3G+
HEL	NHrhfJFHfW6ldHnvckBie3OjeR?=		M3;BTVEhcHJ?		MUXJcohq[mm2aX;uJI9nKFO2YYS1JJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDISWwh[2WubIOgZYZ1\XJiMTDodkBjgSCZZYP0[ZJvKGKub4T0bY5oNCCLQ{WwJF0hOC5yNEGg{txONg>?	M4fCWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
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UKE1	M2POVmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		NEHwSVY1QCCqcoO=		Mo\rS5Jwf3SqIHnubIljcXSrb36gc4YhcHWvYX6gWWtGOSClZXzsd{BmgHC{ZYPzbY5oKEqja{KgWlYyP0ZibYX0ZY51KGGodHXyJFQ5KGi{czDifUBOXFNiYYPzZZktKEeLNUCgQUAxNjB3NDFOwG0v	Ml7rQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzM{iyOFYoRjJzMUO4NlQ3RC:jPh?=
BA/F3	MUjHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?		MoPmOFghcHK\|		M1TJO2dzd3e2aDDpcohq[mm2aX;uJI9nKG2xdYPlJGJCN0Z\|IHPlcIx{KGW6cILld5NqdmdiVHXsMWpCUzJia3nuZZNmKGGodHXyJFQ5KGi{czDifUBOXFNiYYPzZZktKEeLNUCgQUAxNjB4IN88UU4>	NXfOfJFsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxN\|gzPDZpPkKxNVM5OjR4PD;hQi=>
HEL	MkXvSpVv[3Srb36gZZN{[Xl?		M3HDXFEhcHJ?		MmS3TY5pcWKrdHnvckBw\iCVdHH0N{BxcG:\|cHjvdplt[XSrb36gbY4hcHWvYX6gTGVNKGOnbHzzJIFnfGW{IEGgbJIh[nliV3XzeIVzdiCkbH;0eIlv\yxiSVO1NEA:KDBwMEig{txONg>?	NYfjOmR2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxN\|gzPDZpPkKxNVM5OjR4PD;hQi=>
HEL	MoqxS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		MVm0PEBpenN?		MWLHdo94fGhiaX7obYJqfGmxbjDv[kBpfW2jbjDISWwh[2WubIOg[ZhxemW\|c3nu[{BL[Wt{IG[2NVdHKG23dHHueEBi\nSncjC0PEBpenNiYomgUXRUKGG\|c3H5MEBIUTVyIE2gNE4{QSEQvF2u	M2PUbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
BA/F3	MVTHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?		NHziTGo1QCCqcoO=		NXjHNZFwT3Kxd4ToJIlvcGmkaYTpc44hd2ZibX;1d4UhSkFxRkOgZ4VtdHNiZYjwdoV{e2mwZzDU[YwuUkGNMTDrbY5ie2ViYX\0[ZIhPDhiaILzJIJ6KE2WUzDhd5NigSxiR1m1NEA:KDBwNzFOwG0v	M1\LVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
BA/F3	MoDjS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		NIjDUVQ1QCCqcoO=		NFnuUFVIem:5dHigbY5pcWKrdHnvckBw\iCvb4Xz[UBDSS:IMzDj[YxteyCneIDy[ZN{cW6pIGTlcE1VgWt{IHvpcoF{\SCjZoTldkA1QCCqcoOgZpkhVVSVIHHzd4F6NCCJSUWwJF0hOiEQvF2u	M1vE[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
BA/F3	NXjQdXR1T3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=		NXHEXIlkPDhiaILz		M2eycGdzd3e2aDDpcohq[mm2aX;uJI9nKG2xdYPlJGJCN0Z\|IHPlcIx{KGW6cILld5NqdmdiVHXsMWpCUzNia3nuZZNmKGGodHXyJFQ5KGi{czDifUBOXFNiYYPzZZktKEeLNUCgQUAzNjFizszNMi=>	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF\|OEK0Okc,OjFzM{iyOFY9N2F-
UKE1	MlnLSpVv[3Srb36gZZN{[Xl?		NVXzcm5mOSCqch?=		M13hVGlvcGmkaYTpc44hd2ZiU4TheFUheGixc4Doc5J6dGG2aX;uJIlvKGi3bXHuJHVMTTFiY3XscJMh[W[2ZYKgNUBpeiCkeTDX[ZN1\XKwIHLsc5R1cW6p	MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF\|OEK0Okc,OjFzM{iyOFY9N2F-
SW620	M3H3SmNmdGxiY4njcIUh[XO\|YYm=	MoXsN{4{KHWP	M2W2bVI1KGi{cx?=		MoLYR4VtdCCleXPs[UBienKnc4SgbY4hcHWvYX6gV3c3OjBiY3XscJMh[XO\|ZYPz[YQh[XNiYXPjeY12dGG2aX;uJIF1KEd{L12gdIhie2ViYYSgN{4{KHWPIHHmeIVzKDJ2IHjyd{BjgSCobH;3JIN6fG:vZYTyfS=>	NXvre2liRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxN\|gzPDZpPkKxNVM5OjR4PD;hQi=>
HEL	MlnBSpVv[3Srb36gZZN{[Xl?	M2LR[FAvOyC3TR?=	M1:xVlUhdWmwcx?=		Mme0TY5pcWKrdHnvckBw\iCVdHH0OUBxcG:\|cHjvdplt[XSrb36gbY4hcHWvYX6gTGVNKGOnbHzzJIF1KDBwMzD1UUBi\nSncjC1JI1qdnNiYomgW4V{fGW{bjDicI91fGmwZx?=	M2Thb\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
HEL	MoPTSpVv[3Srb36gZZN{[Xl?	NH:3fG4xNjNidV2=	M1vVdVMxKHSxIE[wJI1qdnN?		M13ubWlvcGmkaYTpc44hd2ZiU4TheFUheGixc4Doc5J6dGG2aX;uJIlvKGi3bXHuJGhGVCClZXzsd{BifCByLkOgeW0h[W[2ZYKgN\|AhfG9iNkCgcYlveyCkeTDX[ZN1\XKwIHLsc5R1cW6p	MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF\|OEK0Okc,OjFzM{iyOFY9N2F-
BA/F3	NFXaTWpCdnSrdIXtc5Ih[XO\|YYm=	NX7TZXd4OzBibXevb4c>	MV[xNkBpenN?		MljNRY51cXS3bX;yJIFkfGm4aYT5JIFo[Wmwc4SgcY92e2ViQlGvSlMh[2WubIOg[ZhxemW\|c3nu[{BV\WxvSlHLNkB5\W6xZ4Lh[pRm\CCrbjDOR5IhdW:3c3WgZZN{\XO\|ZXSgZZMhemWmdXP0bY9vKG:oIIDoc5NxcG:{eXzheIVlKFO2YYS1JIxmfmWuIHnuJJNxdGWnbjDheEA{OCCvZz;r[{wheG9iYX\0[ZIhOTJiaILzJIJ6KFenc4Tldo4h[myxdITpcoc>	MYK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF\|OEK0Okc,OjFzM{iyOFY9N2F-
HEL	MYjGeY5kfGmxbjDhd5NigQ>?	NUHjfGYxOC5\|IIXN	MVS1JI1qdnN?		NELaWFRKdmirYnn0bY9vKG:oIGP0ZZQ{KHCqb4PwbI9zgWyjdHnvckBqdiCqdX3hckBJTUxiY3XscJMh[XRiMD6zJJVOKGGodHXyJFUhdWmwczDifUBY\XO2ZYLuJIJtd3S2aX7n	M1;z[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
HEL	NEeybYlHfW6ldHnvckBie3OjeR?=	MnOwNE4{KHWP	NYewUVRVOzBidH:gOlAhdWmwcx?=		MkDSTY5pcWKrdHnvckBw\iCVdHH0N{BxcG:\|cHjvdplt[XSrb36gbY4hcHWvYX6gTGVNKGOnbHzzJIF1KDBwMzD1UUBi\nSncjCzNEB1dyB4MDDtbY5{KGK7IGfld5Rmem5iYnzveJRqdmd?	M1rFS\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
Hs578T	MnjzSpVv[3Srb36gZZN{[Xl?	MVmxJJVO	NVXNV49COjRiaILz		M2DUOGlvcGmkaYTpc44hd2ZiU2TBWFNENW2nZHnheIVlKHS{YX7zZ5JqeHSrb36gbY4hcHWvYX6gTJM2PziWIHPlcIx{KGG2IEGgeW0h[W[2ZYKgNlQhcHK\|IHL5JIx2[2moZYLhd4UhemWyb4L0[ZIh\2WwZTDhd5NigQ>?	NGK5e4E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEm3PFEyOid-MkS5O\|gyOTJ:L3G+
NCI-H1975	M2LZWmZ2dmO2aX;uJIF{e2G7	MmrwNE4xODNidH:gN{B2VQ>?	NXvVfJFlOiCqcoO=		MknuTY5pcWKrdHnvckBw\iCMQVuxJIlvKGi3bXHuJG5EUS2KMUm3OUBk\WyuczDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5iU2TBWFMheGixc4Doc5J6dGG2aX;uJIF1KDBwMECzJJRwKDNidV2gZYZ1\XJiMjDodpMh[nliV3XzeIVzdiCkbH;0JIFv[Wy7c3nz	MoTyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ4MUS0NFgoRjJ4NkG0OFA5RC:jPh?=
HEL 92.1.7	MXnGeY5kfGmxbjDhd5NigQ>?		M{LtZ\|IhcHK\|		M4fS[GlvcGmkaYTpc44hd2ZiSlHLNkBqdiCqdX3hckBJTUxiOUKuNU44KGOnbHzzJIF{e2W\|c3XkJIF{KHKnZIXjeIlwdiCrbjDTWGFVPSCyaH;zdIhwenmuYYTpc44h[W[2ZYKgNkBpenNiYomgW4V{fGW{bjDicI91KGGwYXz5d4l{	MmTvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ4MUS0NFgoRjJ4NkG0OFA5RC:jPh?=
DAOY	NFXlOXFyUFSVIHHzd4F6				MYnxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhTEGRWTDj[Yxtew>?	NXm1[oJjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
SJ-GBM2	M3vxdJFJXFNiYYPzZZk>				M2Hrb5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSj3HRm0zKGOnbHzz	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
A673	NGrTRodyUFSVIHHzd4F6				MVjxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSTZ5MzDj[Yxtew>?	MkPtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-MC	NUDvcII4eUiWUzDhd5NigQ>?				M3TGUpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMW1EKGOnbHzz	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
BT-37	MlHMdWhVWyCjc4PhfS=>				NUTSVGxDeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFLUMVM4KGOnbHzz	Mmr3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
NB-EBc1	MkTudWhVWyCjc4PhfS=>				NFW3VHNyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKtSWJkOSClZXzsdy=>	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
Saos-2	NWXkVWgxeUiWUzDhd5NigQ>?				MofYdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFOjb4OtNkBk\Wyucx?=	MonSQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-SH	NVvBdGJZeUiWUzDhd5NigQ>?				NIW4dFRyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1utUk1UUCClZXzsdy=>	NVe3e4JPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB1643	NGXu[plyUFSVIHHzd4F6				MlnQdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6EMU[0N{Bk\Wyucx?=	NW\sTVZKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
BT-12	NVS1c\|I2eUiWUzDhd5NigQ>?				MYPxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSlRvMUKgZ4VtdHN?	NXzOXGJ1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
OHS-50	MXHxTHRUKGG\|c3H5				MWXxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhV0iVLUWwJINmdGy\|	MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
RD	M4rnSJFJXFNiYYPzZZk>				NX\IV3lleUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLEJINmdGy\|	NE\GTmM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
MG 63 (6-TG R)	MU\xTHRUKGG\|c3H5				MVzxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVUdiNkOgLFYuXEdiUjmgZ4VtdHN?	NWHUPG1FRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh41	MX\xTHRUKGG\|c3H5				M4TQTpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaESxJINmdGy\|	M{W3PVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	p-STAT3 / STAT3 / p-JAK2 / JAK2 ; PubMed: 22027691 Mol Cancer Ther Cells were treated with AZD1480 for the indicated times, lysed and immunoblotted with the indicated antibodies. p-STAT1 / STAT1 / p-STAT5 / STAT5 / p-STAT6 / STAT6 ; PubMed: 22829094 Blood Cancer J Western blot assay of the four HL cell lines treated with increasing doses of AZD1480 (0.1–5 μM) for 72 h. p-ERK / ERK / p-p38 / p38 / SOCS3 / p-SHP2 / SHP2 ; PubMed: 22829094 Blood Cancer J Representative western blot assay showing increased levels of ERK, p38 and SHP-2 phosphorylation in HD-LM2 and L-428, after treatment for 72 h with increasing doses of AZD1480 (0.1-5 μM). In contrast, L-540 showed a dose-dependent inhibition of ERK and p38 activation without increased SHP-2 phosphorylation. SOCS-3 levels decreased in all the cell lines.	22027691 22829094
Immunofluorescence	pSTAT5; PubMed: 30140255 Front Endocrinol (Lausanne) HepG2 cells were incubated in the presence of Pro-Gly (0.5 mM) and/or AZD1480 (1 μM) for 6 h and phospho-STAT5 translocation to nuclei was detected by ICC. Scale bar, 10 μm. The IP and ICC experiments were conducted independently for 3 times, with 3 replicates each time.	30140255
Growth inhibition assay	Cell proliferation ; PubMed: 22027691 Mol Cancer Ther Cells were treated with AZD1480 for the indicated times, and the WST-1 cell proliferation assay performed. The 48 and 72 h time points were statistically significant. Data represent mean ± SD, replicates of three (**, p<0.001; ANOVA). Cell viability; PubMed: 25855603 Blood IL-3-independent Ba/F3 cells were treated with increasing concentrations of the JAK inhibitor AZD1480 showing submicromolar inhibition of proliferation.	22027691 25855603

In vivo

AZD1480 inhibits the STAT3 phosphorylation in an xenograft model of human solid tumors and multiple myeloma. ^[1] In vivo, AZD1480 inhibits the growth of subcutaneous tumors and increases survival of mice bearing intracranial glioblastoma (GBM) tumors by inhibiting STAT-3 activity, indicating that pharmacologic inhibition of the JAK/STAT-3 pathway by AZD1480 should be considered for study in the treatment of patients with GBM tumors. ^[3]AZD1480 blocks lung infiltration of myeloid cells and formation of pulmonary metastases in both mouse syngeneic experimental and spontaneous metastatic models. Furthermore, AZD1480 reduces angiogenesis and metastasis in a human xenograft tumor model. ^[4] The Jak2 inhibitor, AZD1480, suppresses the growth of human solid tumor xenografts harboring persistent Stat3 activity. ^[5]

Protocol

Kinase Assay:^[5]	- Collapse kinase assays: Inhibition studies of AZD1480 are performed using recombinant Jak1, Jak2, or Jak3 under buffer conditions of 50 mM HEPES pH 7.3, 1 mM DTT, 0.01% Tween-20, 50 mM/ml BSA, and 10 mM MgCl₂. Jak3 enzyme is expressed as N-terminal GST fusion in insect cells and purified by glutathione-affinity and size-exclusion chromatographies. Enzymes are assayed in the presence of AZD1480 (10 point dose response, in triplicate, from 8.3 μM to 0.3 nM in half-log dilution steps) using 1.5 μM peptide substrate (Jak1: FITC-C6-KKHTDDGYMPMSPGVA-NH2, Jak2 and Jak3: FAM-SRCtide) and screened under their respective ATP Km (Jak1: 55 μM, Jak2: 15 μM, Jak3: 3 μM) and approximated physiological ATP concentration of 5 mM. Phosphorylated and unphosphorylated peptides are separated and quantified by a Caliper LC3000 system for calculating percent inhibition.
Cell Research:^[4]	- Collapse Cell lines: Renca or 786-O cells, mouse endothelial cells and splenic CD11b⁺/c^-myeloid cells, HUVECs Concentrations: ~1 μM Incubation Time: 48 or 24 hours Method: Renca or 786-O cells are suspended in DMEM medium with 5% FBS , and seeded in 96-well plates (5×10³ per well) to allow adhesion and then treated with DMSO or AZD1480 for 48 hours. Cell viability is determined by MTS assay. Absorbance at 490 nm is measured with Mikrotek Laborsysteme. Mouse endothelial cells and splenic CD11b⁺/c^- myeloid cells are enriched from tumor-bearing mice,and cultured in 5% FBS RPMI-1640 medium. HUVECs are cultured on collagen 1–coated plates in complete medium. All cells are treated with DMSO and AZD1480 at various doses for 24 hours. Cell viability is determined by counting cell number manually. All the experiments are repeated 3 times. (Only for Reference)
Animal Research:^[4]	- Collapse Animal Models: Female BALB/c and athymic nude (NCR ^- nu/nu) mice (7–8 weeks old) Dosages: Once a day at the dose of 50 mg/kg or twice daily at 30 mg/kg Administration: Oral gavage (Only for Reference)

References

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Solubility (25°C)

In vitro	DMSO	69 mg/mL warmed (197.83 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 30% PEG400+0.5% Tween80+5% propylene glycol For best results, use promptly after mixing.	5 mg/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 AZD1480 SDF

Molecular Weight	348.77
Formula	C₁₄H₁₄ClFN₈
CAS No.	935666-88-9
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CC1=CC(=NN1)NC2=NC(=NC=C2Cl)NC(C)C3=NC=C(C=N3)F

In vivo Formulation Calculator (Clear solution)

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

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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

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Working concentration： mg/ml；

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

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

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).

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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
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Computed Result

C1=C0/X	C1:	LOG(C1):
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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
NCT01219543	Terminated	Drug: AZD1480 Daily\|Drug: AZD1480 BID	Solid Tumour\|Advanced Solid Malignancies\|Child-Pugh A to B7 Advanced Hepatocellular Carcinoma\|EGFR and/or ROS Mutant NSCLC\|Lung Metastasis Carcinoma\|Gastric Cancer	AstraZeneca	November 2010	Phase 1
NCT01112397	Terminated	Drug: AZD1480	Solid Malignancies	AstraZeneca	April 2010	Phase 1

Tech Support

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

Handling Instructions

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

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

JAK Signaling Pathway Map

JAK Inhibitors with Unique Features

Pan JAK Inhibitor

Ruxolitinib (INCB018424) : Pan JAK1/2 inhibitor, IC50=3.3 nM/2.8 nM.
FDA-approved JAK Inhibitor

Tofacitinib (CP-690550,Tasocitinib) : Approved by FDA for rheumatoid arthritis (RA).
Newest JAK Inhibitor

XL019 ^New : Potent and selective JAK2 inhibitor with IC50 of 2.2 nM, exhibiting >50-fold selectivity over JAK1, JAK3 and TYK2.
Classic JAK Inhibitor

AG-490 (Tyrphostin B42) : Potent JAK2/3 inhibitor with IC50 of 1.2 nM/1.1 nM; also potent to Aurora A/B, Abl(T315I). Phase 1/2.

Related JAK Products

FLLL32 ^New

FLLL32 is a potent JAK2/STAT3 inhibitor with IC50 of <5 μM. FLLL32 inhibits the induction of STAT3 phosphorylation by IFNα and IL-6 in breast cancer cells.
Cerdulatinib (PRT062070) hydrochloride ^New

Cerdulatinib (PRT-062070, PRT2070) hydrochloride is an oral active, multi-targeted tyrosine kinase inhibitor with IC50 of 12 nM/6 nM/8 nM/0.5 nM and 32 nM for JAK1/JAK2/JAK3/TYK2 and Syk, respectively. Also inhibits 19 other tested kinases with IC50 less than 200 nM.
Ruxolitinib (INCB018424)

Ruxolitinib (INCB018424) is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM in cell-free assays, >130-fold selectivity for JAK1/2 versus JAK3. Ruxolitinib kills tumor cells through toxic mitophagy. Ruxolitinib induces autophagy and enhances apoptosis.
Tofacitinib (CP-690550) Citrate

Tofacitinib citrate (CP-690550, Tasocitinib) is a novel inhibitor of JAK with IC50 of 1 nM, 20 nM and 112 nM against JAK3, JAK2, and JAK1, respectively. Tofacitinib citrate has anti-infection activity.
Tofacitinib (CP-690550)

Tofacitinib (CP-690550,Tasocitinib) is a novel inhibitor of JAK3 with IC50 of 1 nM in cell-free assays, 20- to 100-fold less potent against JAK2 and JAK1. Tofacitinib inhibits the expression of antiapoptotic BCL-A1 and BCL-XL in human plasmacytoid dendritic cells (PDC) and induced PDC apoptosis.
Fedratinib (TG101348)

Fedratinib (SAR302503, TG101348) is a selective inhibitor of JAK2 with IC50 of 3 nM in cell-free assays, 35- and 334-fold more selective for JAK2 versus JAK1 and JAK3. Fedratinib also inhibits FMS-like tyrosine kinase 3 (FLT3) and RET (c-RET) with IC50 of 15 nM and 48 nM, respectively. Fedratinib has potential antineoplastic activity. Fedratinib inhibits proliferation and induces apoptosis. Phase 2.
Momelotinib (CYT387)

Momelotinib (CYT387, LM-1149 , CYT11387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, ~10-fold selectivity versus JAK3. Momelotinib (CYT387) induces apoptosis and autophagy. Phase 3.
WP1066

WP1066 is a novel inhibitor of JAK2 and STAT3 with IC50 of 2.30 μM and 2.43 μM in HEL cells; shows activity to JAK2, STAT3, STAT5, and ERK1/2 not JAK1 and JAK3. WP1066 induces apoptosis. Phase 1.

Features:Similar to its parent compound AG490, WP1066 inhibits the phosphorylation of JAK2, but unlike AG490, WP1066 also degraded JAK2 protein.
Baricitinib (INCB028050)

Baricitinib (LY3009104, INCB028050) is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM in cell-free assays, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2. Baricitinib is found to reduce or interrupt the passage of the virus into target cells and is used in the treatment research for COVID-19. Phase 3.

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AZD1480