AZD1480

For research use only. Not for use in humans.

目录号：S2162

CAS No. 935666-88-9

AZD1480是一种新型，ATP竞争性的JAK2抑制剂，无细胞试验中IC50为0.26 nM，选择性作用于JAK3和Tyk2，对JAK1的作用较弱。Phase 1。

规格

价格

库存

购买数量

10mM (1mL in DMSO)	RMB 1071.19	现货
5mg	RMB 819.48	现货
50mg	RMB 4671.71	现货
大包装	有超大折扣

大剂量询单有大折扣!

今日订购，明日送达，全国免运费！

全国免费电话：400-668-6834 | Email：info@selleck.cn

客户使用Selleck生产的AZD1480发表文献91篇：

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 )

Front Immunol, 2021, 12:661323

PubMed: 34531850 ( 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 )

产品安全说明书

JAK抑制剂选择性比较

生物活性

产品描述

AZD1480是一种新型，ATP竞争性的JAK2抑制剂，无细胞试验中IC50为0.26 nM，选择性作用于JAK3和Tyk2，对JAK1的作用较弱。Phase 1。

特性

AZD1480为治疗多发性骨髓瘤的潜在新型治疗剂。

靶点

JAK2 ^[1]
(Cell-free assay)

0.26 nM

体外研究

5μM AZD1480诱导细胞周期停在G2/M期，且通过抑制Aurora激酶而诱导细胞死亡。^[1]AZD1480是JAK2的有效抑制剂，作用于人类多发性骨髓瘤细胞，可以抑制生长，存活，FGFR3 和 STAT3信号，及下游靶点，包括 Cyclin D2。在低微摩尔浓度时，AZD1480抑制细胞增殖和诱导骨髓瘤细胞系凋亡。^[2]AZD1480 作用于人和鼠神经胶质瘤细胞，有效抑制组成型和诱导型JAK1, JAK2, 及STAT-3的磷酸化作用，结果导致细胞增殖降低，且诱导凋亡。^[3]AZD1480是有效的ATP竞争性的JAK1/2激酶小分子抑制剂，可抑制STAT3磷酸化和肿瘤生长，这种抑制存在STAT3依赖性。AZD1480通过影响肿瘤的微环境而抑制肿瘤血管生成和局部转移。^[4]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
SW620	NGLDeYhHfW6ldHnvckBCe3OjeR?=	NGnYXoQ2KM7:TR?=	MVm0PEBp	NVv6U4RiTE2VTx?=	Mne4Zoxw[2u\|IFrBT\|IwW1SDVEOgd4lodmGuaX7n	MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTl3NEm3OEc,OjV7NUS5O\|Q9N2F-
LoVo	NUHGcHhGTnWwY4Tpc44hSXO\|YYm=	NUHmN3pVPSEQvF2=	NELHboQ1QCCq	M4nNbWROW09?	MkHUZoxw[2u\|IFrBT\|IwW1SDVEOgd4lodmGuaX7n	MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTl3NEm3OEc,OjV7NUS5O\|Q9N2F-
HN5	MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		NHrhcI44OiCq		MofjSWM2OD1\|LkixJOKyKDFwOUmg{txO	M{\QUlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEGwNFExLz5{NUixNFAyODxxYU6=
Cal33	M1PqNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		MWO3NkBp		NYXPZ45RTUN3ME2zMlM4KMLzIECuO\|Uh\|ryP	NGqyXJI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUixNFAyOCd-MkW4NVAxOTB:L3G+
UM-22B	M{HyR2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7		MnvqO\|IhcA>?		Ml;QSWM2OD1{Lk[2JOKyKDBwMkSg{txO	NVu5U3p6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NVAxOTBpPkK1PFExODFyPD;hQi=>
686LN	MYrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		M3:2S\|czKGh?		M4foPWVEPTB;Mj6wOUDDuSBzLkOzJO69VQ>?	NUH3UmV2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NVAxOTBpPkK1PFExODFyPD;hQi=>
UM SCC-1	M2LGdWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		MojvO\|IhcA>?		NWW3[o5ETUN3ME2xMlY4KMLzIECuOFIh\|ryP	MnXQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6MUCwNVAoRjJ3OEGwNFExRC:jPh?=
UM-22A	MkCzS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		Mk\iO\|IhcA>?		NUfXZXNGTUN3ME2xMlMzKMLzIECuN\|kh\|ryP	NIW0Zpg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUixNFAyOCd-MkW4NVAxOTB:L3G+
OSC19	NXXzNZVnT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		NIjFTHg4OiCq		NUTENY1OTUN3ME2xMlI3KMLzIECuNlAh\|ryP	M{\KUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEGwNFExLz5{NUixNFAyODxxYU6=
PCI-52	NFnSXHZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		NF7YSHQ4OiCq		MUPFR\|UxRTFwMECgxtEhOC5yOTFOwG0>	NV6ycoJsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NVAxOTBpPkK1PFExODFyPD;hQi=>
PCI-15B	M1X4TGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		MmnhO\|IhcA>?		M331V2VEPTB;MD65PUDDuSBzLke0JO69VQ>?	M1HuTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEGwNFExLz5{NUixNFAyODxxYU6=
UMSCC-1	NVL2[npHTnWwY4Tpc44hSXO\|YYm=	MoXZNE4xODB3LUGuOkDPxE1?	MVSyOEBp		NWLUZZZ4[WK{b3fheIV{KEmOLUdihLNqdmS3Y3XkJJVxNXKnZ4XsZZRqd25ib3[gdHNVSVR\|VInyO\|A2yqCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?	NXLIfnl3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NVAxOTBpPkK1PFExODFyPD;hQi=>
Cal33	MWrGeY5kfGmxbjDBd5NigQ>?	MXmwMlAxODVvMz64JO69VQ>?	NGnRfFczPCCq		MorPZYJzd2ejdHXzJGlNNTckgKPpcoR2[2WmIIXwMZJm\3WuYYTpc44hd2ZicGPURXQ{XHm{N{C1xsBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPThzMECxNEc,OjV6MUCwNVA9N2F-
HH5	MVLGeY5kfGmxbjDBd5NigQ>?	NHPyeoUxNjByMEWtN{45KM7:TR?=	M1XVNlI1KGh?		MXrhZpJw\2G2ZYOgTWwuPuLCk3nu[JVk\WRidYCtdoVofWyjdHnvckBw\iCyU2TBWFNVgXJ5MEZCpIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy	NWDUUZp5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NVAxOTBpPkK1PFExODFyPD;hQi=>
UM-22A	Mor0SpVv[3Srb36gRZN{[Xl?	MVGwMlAxODVvMT62JO69VQ>?	M{TDNFI1KGh?		MoTsZYJzd2ejdHXzJGlNNTckgKPpcoR2[2WmIIXwMZJm\3WuYYTpc44hd2ZicGPURXQ{XHm{N{C1xsBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPThzMECxNEc,OjV6MUCwNVA9N2F-
A1847	NX3VZ\|hvTnWwY4Tpc44hSXO\|YYm=	NXXEe4tGOC5yNT2xNEDPxE1?	MUeyOEBp	NHjjXHJFVVORwrC=	MYPy[YR2[2W\|IIDoc5NxcG:{eXzheIVlKFOWQWSzJIxmfmWucx?=	M3;zVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkS2NFE2Lz5{NU[0OlAyPTxxYU6=
OVCAR-5	NYKzU3pOTnWwY4Tpc44hSXO\|YYm=	NXjZZ3hbOC5yNT2xNEDPxE1?	NFTm[24zPCCq	MVvEUXNQyqB?	Mmi1doVlfWOnczDwbI9{eGixconsZZRm\CCVVFHUN{Bt\X[nbIO=	NETlPII9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[0OlAyPSd-MkW2OFYxOTV:L3G+
OVCAR-8	MU\GeY5kfGmxbjDBd5NigQ>?	M4LyXFAvODVvMUCg{txO	M4PtXVI1KGh?	MWfEUXNQyqB?	M1zsT5Jm\HWlZYOgdIhwe3Cqb4L5cIF1\WRiU2TBWFMhdGW4ZXzz	NUDLOXdVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2OFYxOTVpPkK1OlQ3ODF3PD;hQi=>
MOVCAR-5447	MXTGeY5kfGmxbjDBd5NigQ>?	NUjzNZU{OC5yNT2xNEDPxE1?	NHLCfFAzPCCq	NGiyWolFVVORwrC=	M3fMZZJm\HWlZYOgdIhwe3Cqb4L5cIF1\WRiU2TBWFMhdGW4ZXzz	NXTESIFnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2OFYxOTVpPkK1OlQ3ODF3PD;hQi=>
MOVCAR-5009	MnHoSpVv[3Srb36gRZN{[Xl?	NHjwNVExNjB3LUGwJO69VQ>?	M{DpWVI1KGh?	MVPEUXNQyqB?	Mlz3doVlfWOnczDwbI9{eGixconsZZRm\CCVVFHUN{Bt\X[nbIO=	NFXp[mw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[0OlAyPSd-MkW2OFYxOTV:L3G+
A1847	M4DtWmNmdGxiVnnhZoltcXS7IFHzd4F6	NW\aeG9sOC5yNT2xNEDPxE1?	MX63NkBp	NITpSZhFVVOR	NWXGbpJmemWmdXPld{Bk\WyuII\pZYJqdGm2eTDheEB1cGViY3;uZ4VzdnS{YYTpc44hd2ZiNTFOwG0>	NE\YZ449[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[0OlAyPSd-MkW2OFYxOTV:L3G+
OVCAR-5	MV\D[YxtKF[rYXLpcIl1gSCDc4PhfS=>	MlHjNE4xPS1zMDFOwG0>	NWO4XXE{PzJiaB?=	NWrvcI1LTE2VTx?=	NWjaWVBZemWmdXPld{Bk\WyuII\pZYJqdGm2eTDheEB1cGViY3;uZ4VzdnS{YYTpc44hd2ZiNTFOwG0>	NXzPVJZ6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2OFYxOTVpPkK1OlQ3ODF3PD;hQi=>
OVCAR-8	NXPjWGRWS2WubDDWbYFjcWyrdImgRZN{[Xl?	NEPGVYoxNjB3LUGwJO69VQ>?	MXe3NkBp	MV;EUXNQ	Mn;2doVlfWOnczDj[YxtKH[rYXLpcIl1gSCjdDD0bIUh[2:wY3XycpRz[XSrb36gc4YhPSEQvF2=	M3TMcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkS2NFE2Lz5{NU[0OlAyPTxxYU6=
OVCAR-5	NIDPdmRCeG:ydH;zbZMhSXO\|YYm=	NHvUdHkxNjVxMT:1JO69VQ>?	MnPBOFghcA>?	NUO4V4lrTE2VTx?=	MmPubY5lfWOnczDzbYdvcW[rY3HueEBieG:ydH;zbZMh[XRiaHnnbEBkd26lZYLueJJifGmxbh?=	M3X0fFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkS2NFE2Lz5{NU[0OlAyPTxxYU6=
OVCAR-8	NE\3cVVCeG:ydH;zbZMhSXO\|YYm=	NGTpdIwxNjVxMT:1JO69VQ>?	NITPd2o1QCCq	M1\BcWROW09?	MX\pcoR2[2W\|IIPp[45q\mmlYX70JIFxd3C2b4Ppd{BifCCqaXfoJINwdmOncn70doF1cW:w	M{TrSFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkS2NFE2Lz5{NU[0OlAyPTxxYU6=
AKRSL	NYDSZY1CS2WubDDWbYFjcWyrdImgRZN{[Xl?		MmO0O\|IhcA>?		NELjbmdKSzVy78{eNVAh\|ryP	MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTVyNE[zOUc,OjV3MES2N\|U9N2F-
PALJDL	M4e4Z2NmdGxiVnnhZoltcXS7IFHzd4F6		NVrHeHY1PzJiaB?=		NVfkZnR6UUN3ME2yMlQh\|ryP	NVW2TGtzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW1NFQ3OzVpPkK1OVA1PjN3PD;hQi=>
MO4	NVjPeVNWTnWwY4Tpc44hSXO\|YYm=	M3:0fVAvPS9zL{Wg{txO	NXXPWWdpPiCq		Mn3IbY5pcWKrdIOgVE1UXEGWMzDlfJBz\XO\|aX;uxsA>	NGTOcHU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUG0PVU{PSd-MkWxOFk2OzV:L3G+
DU145	NG\nUmtHfW6ldHnvckBCe3OjeR?=	NELofHoxNTJyMDDuUS=>	MUKxJIjDqA>?		M1rnZ5N2eHC{ZYPz[ZMhUUxvNj3hZ5RqfmG2ZXSgV5RifDNiYX7kJGVTUzFxMjDzbYdv[Wyrbne=	NFfKeYI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEW3O\|k1Oid-MkS1O\|c6PDJ:L3G+
DU145	Mnj5SpVv[3Srb36gRZN{[Xl?	NXPtfpl1QDByIH7N	NGK4SoU4OiCq		MWTzeZBxemW\|c3XzJGlNNTZvaX7keYNm\CCvaXfyZZRwenl?	NITwOYw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEW3O\|k1Oid-MkS1O\|c6PDJ:L3G+
CWR22Rv1	Ml3FSpVv[3Srb36gRZN{[Xl?	Ml;aPFAxKG6P	Mn7ZO\|IhcA>?		MUjzeZBxemW\|c3XzJGlNNTZvaX7keYNm\CCvaXfyZZRwenl?	M12xelxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NUe3PVQzLz5{NEW3O\|k1OjxxYU6=
N592	NGW3SWlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=				MkLpTWM2OD1yLki0JO69VQ>?	M4LQZ\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MUW4O\|AyLz5{NEG1PFcxOTxxYU6=
H82	NIPFeZFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=				M4HNNGlEPTB;MT6zO{DPxE1?	MmLzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzNUi3NFEoRjJ2MUW4O\|AyRC:jPh?=
GLC4	NUnFSGZXT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=				NILIeHhKSzVyPUGuO\|kh\|ryP	NYLlWld6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSxOVg4ODFpPkK0NVU5PzBzPD;hQi=>
H526	MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?				M{jXemlEPTB;Mz6wPEDPxE1?	M3X4elxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MUW4O\|AyLz5{NEG1PFcxOTxxYU6=
H1173	MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?				MVvJR\|UxRTJwM{mg{txO	M{HEblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MUW4O\|AyLz5{NEG1PFcxOTxxYU6=
DMS114	NV;aWJBsT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=				NXLx[HBXUUN3ME2wMlc{KM7:TR?=	MkjEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzNUi3NFEoRjJ2MUW4O\|AyRC:jPh?=
NCI-N592	MV7GeY5kfGmxbjDBd5NigQ>?	NI[1bVYxNjNxMT:zJO69VQ>?	NGW3XZYzPCCq		M1f0fYlv\HWlZYOgS\|IwVSClZXzsJIN6[2ynIHHydoV{fA>?	MlHFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzNUi3NFEoRjJ2MUW4O\|AyRC:jPh?=
GLC4	M1S0O2Z2dmO2aX;uJGF{e2G7	M2DiXVAvOy9zL{Og{txO	MXOyOEBp		NHrMR3NqdmS3Y3XzJGczN01iY3XscEBkgWOuZTDhdpJme3R?	NFr6O\|Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEG1PFcxOSd-MkSxOVg4ODF:L3G+
NCI-H82	MlXmSpVv[3Srb36gRZN{[Xl?	MXSwMlMwOS9\|IN88US=>	M3zrSFI1KGh?		Mn36bY5lfWOnczDHNk9OKGOnbHygZ5lkdGViYYLy[ZN1	M3L0RVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MUW4O\|AyLz5{NEG1PFcxOTxxYU6=
NCI-N592	M4jWNGFxd3C2b4Ppd{BCe3OjeR?=	MnHVNE4{NzFxMzFOwG0>	NHrWOpo1QCCq		MkHKbY5kemWjc3XzJJRp\SCuZY\lcEBw\iClbHXheoVlNUOjc4Dhd4UhOw>?	MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF3OEewNUc,OjRzNUi3NFE9N2F-
GLC4	MXXBdI9xfG:\|aYOgRZN{[Xl?	NUXlSXIzOC5\|L{GvN{DPxE1?	NIT3Uo81QCCq		M1rwVolv[3KnYYPld{B1cGVibHX2[Ywhd2ZiY3zlZZZm\C2FYYPwZZNmKDN?	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF3OEewNUc,OjRzNUi3NFE9N2F-
NCI-H82	MoHLRZBweHSxc3nzJGF{e2G7	Mn;wNE4{NzFxMzFOwG0>	MXq0PEBp		NF64UJZqdmO{ZXHz[ZMhfGinIHzleoVtKG:oIHPs[YF3\WRvQ3HzdIF{\SB\|	NFrsdIw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEG1PFcxOSd-MkSxOVg4ODF:L3G+
CWR22Rv1	NH;wNJVCeG:ydH;zbZMhSXO\|YYm=				MmLPTWM2OD1yLkS4NkDPxE1?	MmTLQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7NEKwPVUoRjJ\|OUSyNFk2RC:jPh?=
CWR22Pc	MmrNRZBweHSxc3nzJGF{e2G7				NYfVc45WUUN3ME2wMlQ{QCEQvF2=	M3jIO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OUSyNFk2Lz5{M{m0NlA6PTxxYU6=
PC-3	NFLkO4xCeG:ydH;zbZMhSXO\|YYm=				MV3JR\|UxRTFwN{W1JO69VQ>?	NELNVIk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{m0NlA6PSd-MkO5OFIxQTV:L3G+
DU145	NFfHUYVCeG:ydH;zbZMhSXO\|YYm=				NV\sXoluUUN3ME2zMlUyPyEQvF2=	M3z6O\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|OUSyNFk2Lz5{M{m0NlA6PTxxYU6=
RC165N	NYfzPG5[SXCxcITvd4l{KEG\|c3H5				MYfJR\|UxRTJwMEizJO69VQ>?	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzl2MkC5OUc,OjN7NEKwPVU9N2F-
ARPE19	M2frXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			M{S0O2ROW09?	MkTGTWM2OD1{ND6zPEDPxE1?	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
HEK293	Mnf2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NXzIeI56TE2VTx?=	M3iwXWlEPTB;OD62O{DPxE1?	M3PFTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NUOxPVIyLz5{M{WzNVkzOTxxYU6=
KCNR	NUjpN4NQT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			Mmq1SG1UVw>?	NWLKe29sUUN3ME2wMlQ3KM7:TR?=	MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
SY5Y	MnfGS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			Mmn3SG1UVw>?	MnrSTWM2OD1yLkO2JO69VQ>?	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
BE2	M3[0Xmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			M1rXbGROW09?	MYjJR\|UxRTBwN{Gg{txO	MXe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
AS	NUG1VoUyT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			M3HkfGROW09?	M3uzeGlEPTB;MT61N{DPxE1?	NWDhWm55RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
NGP	MoPVS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MVXEUXNQ	M1zPOWlEPTB;MD61OkDPxE1?	NUTPfYtxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
IMR32	M4TzNmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			M4PmNmROW09?	MoHITWM2OD1yLk[2JO69VQ>?	NWL6d45oRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
LAN5	M2X3Vmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NVn1bXpETE2VTx?=	MoDKTWM2OD1zLkC0JO69VQ>?	NHn1[\|A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N\|E6OjF:L3G+
RH18	MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NXHFU2RxTE2VTx?=	MnvnTWM2OD1zLkSyJO69VQ>?	MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
RH30	NWXRXZhlT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NYPmR4d7TE2VTx?=	NGHudGtKSzVyPUGuNlUh\|ryP	NWfBfHg3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
RH17	Ml71S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			M1z3SmROW09?	NHOwcphKSzVyPUKuOVEh\|ryP	NGe0e5A9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N\|E6OjF:L3G+
RH28	M13nUGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MkDCSG1UVw>?	NGnDO5VKSzVyPUSuNlgh\|ryP	MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
RH36	MUDHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MYLEUXNQ	NGTHUFlKSzVyPUWuN\|ch\|ryP	NVfFU5N4RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
RH41	MXzHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			M2LWfGROW09?	NGXXUnRKSzVyPUCuOFgh\|ryP	NWW4WHZIRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
RD	NYi0eWx[T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			NIXxXoNFVVOR	MoHnTWM2OD12LkOyJO69VQ>?	NGnmTFc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N\|E6OjF:L3G+
TC32	M4fMcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MWTEUXNQ	MU\JR\|UxRTNwOEWg{txO	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
TC71	MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			MV7EUXNQ	NX\vTHAxUUN3ME20MlM{KM7:TR?=	NHPsc2U9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N\|E6OjF:L3G+
KCNR	M2DBU2Fxd3C2b4Ppd{BCe3OjeR?=	M4q5WVAvPS9zLkCvNk42KM7:TR?=	NI\jfogzPCCq	MmLNSG1UVw>?	MXXpcoR2[2W\|IHHuJIlv[3KnYYPlJIlvKGOjc4Dhd4UhOy95IHHjeIl3cXS7	NWfSbnZbRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
SY5Y	NGTiSFZCeG:ydH;zbZMhSXO\|YYm=	Ml20NE42NzFwMD:yMlUh\|ryP	NXHaTHc6OjRiaB?=	NULsOI9yTE2VTx?=	M1joPYlv\HWlZYOgZY4hcW6lcnXhd4UhcW5iY3HzdIF{\SB\|L{egZYN1cX[rdIm=	MkPUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ\|NUOxPVIyRC:jPh?=
Rh18	MUPBdI9xfG:\|aYOgRZN{[Xl?	MVWwMlUwOS5yL{KuOUDPxE1?	NFjvbG4zPCCq	MlzxSG1UVw>?	NVL4WoIxcW6mdXPld{BidiCrbnPy[YF{\SCrbjDjZZNx[XOnIEOvO{Bi[3Srdnn0fS=>	MVS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
TC32	MVXBdI9xfG:\|aYOgRZN{[Xl?	M{XV[\|AvPS9zLkCvNk42KM7:TR?=	MX6yOEBp	NV3xdIZMTE2VTx?=	NWrj[ph2cW6mdXPld{BidiCrbnPy[YF{\SCrbjDjZZNx[XOnIEOvO{Bi[3Srdnn0fS=>	NUTSNYUzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
KCNR	M3\pZWZ2dmO2aX;uJGF{e2G7	NIfzbmUxNjVxMT6wM\|IvPS93IN88US=>	NGK1dGczPCCq	MULEUXNQ	NV7MflNrcW6qaXLpeJMh[m:2aDDlcoRw\2Wwb4XzJINwdnO2aYT1eIl3\SCjbnSgTWwuPi2rbnT1Z4VlKFOWQWSzJIFkfGm4YYTpc44>	NHvEOY89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N\|E6OjF:L3G+
SY5Y	MXjGeY5kfGmxbjDBd5NigQ>?	NHi1SXQxNjVxMT6wM\|IvPS93IN88US=>	M2\sUFI1KGh?	NFLvVmpFVVOR	MYTpcohq[mm2czDic5RpKGWwZH;n[Y5wfXNiY3;ud5RqfHW2aY\lJIFv\CCLTD22MYlv\HWlZXSgV3RCXDNiYXP0bZZifGmxbh?=	MkP2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ\|NUOxPVIyRC:jPh?=
Rh18	NU\sUpVrTnWwY4Tpc44hSXO\|YYm=	NFy4WocxNjVxMT6wM\|IvPS93IN88US=>	MXOyOEBp	M17pZWROW09?	M{XCXolvcGmkaYTzJIJwfGhiZX7kc4dmdm:3czDjc45{fGm2dYTpeoUh[W6mIFnMMVYucW6mdXPl[EBUXEGWMzDhZ5RqfmG2aX;u	NWO3colERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
TC32	M3TWTWZ2dmO2aX;uJGF{e2G7	MYewMlUwOS5yL{KuOU82KM7:TR?=	MYKyOEBp	MXjEUXNQ	NF3UcYxqdmirYnn0d{Bjd3SqIHXu[I9o\W6xdYOgZ49ve3SrdIX0bZZmKGGwZDDJUE03NWmwZIXj[YQhW1SDVEOgZYN1cX[jdHnvci=>	Mnq3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ\|NUOxPVIyRC:jPh?=
TPC-1	MVHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NYf2W3pYOSEEtV2=	NUDMfG05OC12IHS=	M3zEemROW09?	NFr0eIhqdmirYnn0d{Bk\WyuIHfyc5d1cCCjZoTldkAzKGRidILlZZRu\W62	NYj5SZByRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOwOVY1QTlpPkKzNFU3PDl7PD;hQi=>
MZ-CRC1	MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	MVKxJOK2VQ>?	MnfhNE02KGR?	NIT4RYRFVVOR	MULpcohq[mm2czDj[YxtKGe{b4f0bEBi\nSncjCxJIQhfHKnYYTt[Y51	M2rHUlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|MEW2OFk6Lz5{M{C1OlQ6QTxxYU6=
TT	MWLHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M{TpdFEhyrWP	M3;aRVAuPCCm	MlvQSG1UVw>?	MmnabY5pcWKrdIOgZ4VtdCCpcn;3eIgh[W[2ZYKgNUBlKHS{ZXH0cYVvfA>?	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzB3NkS5PUc,OjNyNU[0PVk9N2F-
TPC-1	NXzmeHhDTnWwY4Tpc44hSXO\|YYm=	MX:xJOK2VQ>?	MormO\|IhcA>?	MknWSG1UVw>?	MlHDbY5lfWOnczDHNUBjdG:la3Hn[S=>	M4LmNlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|MEW2OFk6Lz5{M{C1OlQ6QTxxYU6=
MZ-CRC1	MmrSSpVv[3Srb36gRZN{[Xl?	M3THZ\|EhyrWP	Mny5O\|IhcA>?	NHfGSFZFVVOR	NUnvU4xqcW6mdXPld{BIOSCkbH;jb4Fo\Q>?	NF3aU5Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{C1OlQ6QSd-MkOwOVY1QTl:L3G+
TT	NIDIb4dHfW6ldHnvckBCe3OjeR?=	NInZWmgyKML3TR?=	MVW3NkBp	MYjEUXNQ	NE\yOHZqdmS3Y3XzJGcyKGKub3PrZYdm	M1WwblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|MEW2OFk6Lz5{M{C1OlQ6QTxxYU6=
MZ-CRC1	MYTBdI9xfG:\|aYOgRZN{[Xl?	M3HneFEhyrWP	M37uclQ5KGh?	NF;qVVNFVVOR	Ml[4bY5lfWOnczDhdI9xfG:\|aYO=	MoCyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjNyNU[0PVkoRjJ\|MEW2OFk6RC:jPh?=
TT	Mm[xRZBweHSxc3nzJGF{e2G7	M1PDelEhyrWP	NHr6[VE1QCCq	M1S0OWROW09?	MWfpcoR2[2W\|IHHwc5B1d3Orcx?=	MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzB3NkS5PUc,OjNyNU[0PVk9N2F-
HD-LM2	M1;zRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		M3XFOVcz6oDLaB?=	MlfHSG1UVw>?	NFK2d4xKSzVyPUeuPFQ1KM7:TR?=	NHfwdVA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkiyPVA6PCd-MkK4NlkxQTR:L3G+
L-428	NGnBWoVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		M{PLe\|cz6oDLaB?=	M1jCcGROW09?	MonBTWM2OD15Lkm0O{DPxE1?	M1XzXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OEK5NFk1Lz5{MkiyPVA6PDxxYU6=
KM-H2	MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		MX:3NwKBkWh?	M2jy[GROW09?	NV\hcIQyUUN3ME2xMlMxQCEQvF2=	M4jqb\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OEK5NFk1Lz5{MkiyPVA6PDxxYU6=
L-540	NVjlXHdbT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		M2\QS\|cz6oDLaB?=	M2fLfWROW09?	MlfYTWM2OD16LkKxOkDPxE1?	M{\lclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OEK5NFk1Lz5{MkiyPVA6PDxxYU6=
HD-LM2	NWLtfnJTTnWwY4Tpc44hSXO\|YYm=	MljkNE4yNzBwNT:xM\|Uh\|ryP	MmLGO\|LjiImq	MVTEUXNQ	MV;pcohq[mm2czDTWGFVOyxiU2TBWFUh[W6mIGPURXQ3KHCqb4PwbI9zgWyjdHnvci=>	M{PnelxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OEK5NFk1Lz5{MkiyPVA6PDxxYU6=
L-428	MmfOSpVv[3Srb36gRZN{[Xl?	NYjFU21oOC5zL{CuOU8yNzVizszN	MY[3NwKBkWh?	MULEUXNQ	NFTRTGhqdmirYnn0d{BUXEGWMzygV3RCXDViYX7kJHNVSVR4IIDoc5NxcG:{eXzheIlwdg>?	M{DwSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OEK5NFk1Lz5{MkiyPVA6PDxxYU6=
KM-H2	NYD3O5hZTnWwY4Tpc44hSXO\|YYm=	MUCwMlEwOC53L{GvOUDPxE1?	MXe3NwKBkWh?	M3zMVGROW09?	NUHQc3NwcW6qaXLpeJMhW1SDVEOsJHNVSVR3IHHu[EBUXEGWNjDwbI9{eGixconsZZRqd25?	MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjh{OUC5OEc,OjJ6MkmwPVQ9N2F-
L-540	NH3EUldHfW6ldHnvckBCe3OjeR?=	MonUNE4yNzBwNT:xM\|Uh\|ryP	M37lW\|cz6oDLaB?=	M4HRdWROW09?	MXjpcohq[mm2czDTWGFVOyxiU2TBWFUh[W6mIGPURXQ3KHCqb4PwbI9zgWyjdHnvci=>	M3;NUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OEK5NFk1Lz5{MkiyPVA6PDxxYU6=
HD-LM2	MXnBdI9xfG:\|aYOgRZN{[Xl?	NHXpU2syNzVizszN	MXy3NwKBkWh?	MU\EUXNQ	NIP1fINqdmS3Y3XzJIFxd3C2b4Ppdy=>	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjh{OUC5OEc,OjJ6MkmwPVQ9N2F-
L-428	Mn;4RZBweHSxc3nzJGF{e2G7	NHXlc5AyNzVizszN	NULhNoNSPzMkgJno	NFrvSnBFVVOR	M4Lle4lv\HWlZYOgZZBweHSxc3nz	MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjh{OUC5OEc,OjJ6MkmwPVQ9N2F-
KM-H2	NGDLPFJCeG:ydH;zbZMhSXO\|YYm=	MknNNU82KM7:TR?=	MUC3NwKBkWh?	M33ZVmROW09?	MkCybY5lfWOnczDhdI9xfG:\|aYO=	M4nsUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OEK5NFk1Lz5{MkiyPVA6PDxxYU6=
L-540	MVjBdI9xfG:\|aYOgRZN{[Xl?	NIT3NFQyNzVizszN	NU\LWYdRPzMkgJno	MoPCSG1UVw>?	NGjKd41qdmS3Y3XzJIFxd3C2b4Ppdy=>	MmDlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ6MkmwPVQoRjJ{OEK5NFk1RC:jPh?=
U251-MG	NHnBWHBHfW6ldHnvckBCe3OjeR?=	NUnvSmFsOSEEtV2=	M{exNFAuOTZiaB?=		MnTJbY5pcWKrdIOgZ49ve3SrdIX0bZZmKFOWQWStN{BidmRiSlHLNkBi[3SrdnH0bY9v	M2jFXVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MEK3OlkyLz5{MkCyO\|Y6OTxxYU6=
U87-MG	NGq1PXNHfW6ldHnvckBCe3OjeR?=	NXLDWoUyOSEEtV2=	M{jQc\|AuOTZiaB?=		MVLpcohq[mm2czDjc45{fGm2dYTpeoUhW1SDVD2zJIFv\CCMQVuyJIFkfGm4YYTpc44>	M1fKRVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MEK3OlkyLz5{MkCyO\|Y6OTxxYU6=
4C8	MlPqSpVv[3Srb36gRZN{[Xl?	M4X0R\|EhyrWP	NFHwVHkxNTF4IHi=		MXrpcohq[mm2czDjc45{fGm2dYTpeoUhW1SDVD2zJIFv\CCMQVuyJIFkfGm4YYTpc44>	M{jDWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MEK3OlkyLz5{MkCyO\|Y6OTxxYU6=
U251-MG	NX[xdFA2T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	Ml;pNU8yOCEEtV2=	MY[yOE81QC95MjDo		MojsbY5pcWKrdIOgZ4VtdCCycn;sbYZmemG2aX;uJIF1KGFiY3;uZ4VvfHKjdHnvckBw\iBzMDFCuW0>	MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjB{N{[5NUc,OjJyMke2PVE9N2F-
U87-MG	NGDrfJlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MVixM\|ExKML3TR?=	NYrBXFlTOjRxNEivO\|IhcA>?		Ml;ybY5pcWKrdIOgZ4VtdCCycn;sbYZmemG2aX;uJIF1KGFiY3;uZ4VvfHKjdHnvckBw\iBzMDFCuW0>	NULLNmVERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKwNlc3QTFpPkKyNFI4PjlzPD;hQi=>
4C8	NY\WdIs4T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MorINU8yOCEEtV2=	M2Gy[VI1NzR6L{eyJIg>		MYHpcohq[mm2czDj[YxtKHC{b3zp[oVz[XSrb36gZZQh[SClb37j[Y51emG2aX;uJI9nKDFyINM1US=>	NYPLeIlLRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKwNlc3QTFpPkKyNFI4PjlzPD;hQi=>
U266	MnnWRZBweHSxc3nzJGF{e2G7	MX[wMlUuOiEQvF2=	MVO0PE84OiCq		NX:2[Jp7cW6mdXPld{BieG:ydH;zbZMh\G:\|ZTDk[ZBmdmSnboTsfS=>	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF4NEWxO{c,OjFzNkS1NVc9N2F-
Kms.11	NEjpSGdCeG:ydH;zbZMhSXO\|YYm=	M2PK[FAvPS1{IN88US=>	NInTRYQ1QC95MjDo		Mn\PbY5lfWOnczDhdI9xfG:\|aYOg[I9{\SCmZYDlcoRmdnSueR?=	NUDKPVRMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxOlQ2OTdpPkKxNVY1PTF5PD;hQi=>
8226	MWrBdI9xfG:\|aYOgRZN{[Xl?	MVuwMlUuOiEQvF2=	NVLlcox5PDhxN{KgbC=>		Mn;HbY5lfWOnczDhdI9xfG:\|aYOg[I9{\SCmZYDlcoRmdnSueR?=	NWXPOYVuRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxOlQ2OTdpPkKxNVY1PTF5PD;hQi=>
SET2	NIWwZZdIem:5dHigbY5pcWKrdHnvckBie3OjeR?=		M1fMNFQ5KGi{cx?=		MUPHdo94fGhiaX7obYJqfGmxbjDv[kBpfW2jbjDTSXQzKGOnbHzzJIV5eHKnc4PpcochUmGtMjDWOlE4TiCvdYThcpQh[W[2ZYKgOFghcHK\|IHL5JG1VWyCjc4PhfUwhT0l3MDC9JFAvODF4IN88UU4>	M2HuVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
SET2	MULGeY5kfGmxbjDhd5NigQ>?		MYqxJIhz		M4fjVGlvcGmkaYTpc44hd2ZiU4TheFMheGixc4Doc5J6dGG2aX;uJIlvKGi3bXHuJHNGXDJiY3XscJMh[W[2ZYKgNUBpeiCkeTDX[ZN1\XKwIHLsc5R1cW6pLDDJR\|UxKD1iMD6wNlMh\|ryPLh?=	MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF\|OEK0Okc,OjFzM{iyOFY9N2F-
SET2	NUHuTYhLTnWwY4Tpc44h[XO\|YYm=		M2eybFEhcHJ?		NFf2UmNKdmirYnn0bY9vKG:oIGP0ZZQ2KHCqb4PwbI9zgWyjdHnvckBqdiCqdX3hckBUTVR{IHPlcIx{KGGodHXyJFEhcHJiYomgW4V{fGW{bjDicI91fGmwZzygTWM2OCB;IECuNFI2KM7:TT6=	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF\|OEK0Okc,OjFzM{iyOFY9N2F-
HEL	MnPHSpVv[3Srb36gZZN{[Xl?		NVjLb2lsOSCqch?=		Ml33TY5pcWKrdHnvckBw\iCVdHH0OUBxcG:\|cHjvdplt[XSrb36gbY4hcHWvYX6gTGVNKGOnbHzzJIFnfGW{IEGgbJIh[nliV3XzeIVzdiCkbH;0eIlv\yxiSVO1NEA:KDBwMESxJO69VS5?	NFnnbFc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUGzPFI1Pid-MkGxN\|gzPDZ:L3G+
Ba/F3	M1K1WmZ2dmO2aX;uJIF{e2G7				NF3rc3lKdmirYnn0bY9vKG:oIGP0ZZQ2KHCqb4PwbI9zgWyjdHnvckBqdiCvb4Xz[UBD[S:IMzDj[YxteyCneIDy[ZN{cW6pIGTFUE1L[Wt{LDDJR\|UxKD1iMD6wOFYh\|ryPLh?=	MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF\|OEK0Okc,OjFzM{iyOFY9N2F-
UKE1	NHfEZmtIem:5dHigbY5pcWKrdHnvckBie3OjeR?=		NWPzOHpkPDhiaILz		MmPGS5Jwf3SqIHnubIljcXSrb36gc4YhcHWvYX6gWWtGOSClZXzsd{BmgHC{ZYPzbY5oKEqja{KgWlYyP0ZibYX0ZY51KGGodHXyJFQ5KGi{czDifUBOXFNiYYPzZZktKEeLNUCgQUAxNjB3NDFOwG0v	Ml;qQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzM{iyOFYoRjJzMUO4NlQ3RC:jPh?=
BA/F3	MX7Hdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?		MYW0PEBpenN?		NV3PcnFMT3Kxd4ToJIlvcGmkaYTpc44hd2ZibX;1d4UhSkFxRkOgZ4VtdHNiZYjwdoV{e2mwZzDU[YwuUkGNMjDrbY5ie2ViYX\0[ZIhPDhiaILzJIJ6KE2WUzDhd5NigSxiR1m1NEA:KDBwME[g{txONg>?	MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF\|OEK0Okc,OjFzM{iyOFY9N2F-
HEL	NU\acGZrTnWwY4Tpc44h[XO\|YYm=		M{TucVEhcHJ?		NIj4fI1KdmirYnn0bY9vKG:oIGP0ZZQ{KHCqb4PwbI9zgWyjdHnvckBqdiCqdX3hckBJTUxiY3XscJMh[W[2ZYKgNUBpeiCkeTDX[ZN1\XKwIHLsc5R1cW6pLDDJR\|UxKD1iMD6wPEDPxE1w	M3;nT\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
HEL	NGLOV5ZIem:5dHigbY5pcWKrdHnvckBie3OjeR?=		MkTnOFghcHK\|		NUj1cW5yT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hUEWOIHPlcIx{KGW6cILld5NqdmdiSnHrNkBXPjF5RjDteZRidnRiYX\0[ZIhPDhiaILzJIJ6KE2WUzDhd5NigSxiR1m1NEA:KDBwM{mg{txONg>?	MkHhQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzM{iyOFYoRjJzMUO4NlQ3RC:jPh?=
BA/F3	M17Y[Gdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		NXLocXQ1PDhiaILz		MkHsS5Jwf3SqIHnubIljcXSrb36gc4YhdW:3c3WgRmEwTjNiY3XscJMh\XiycnXzd4lv\yCWZXytTmFMOSCtaX7hd4Uh[W[2ZYKgOFghcHK\|IHL5JG1VWyCjc4PhfUwhT0l3MDC9JFAvPyEQvF2u	MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF\|OEK0Okc,OjFzM{iyOFY9N2F-
BA/F3	NI\XTpBIem:5dHigbY5pcWKrdHnvckBie3OjeR?=		NFXlWFE1QCCqcoO=		NUew[Y5CT3Kxd4ToJIlvcGmkaYTpc44hd2ZibX;1d4UhSkFxRkOgZ4VtdHNiZYjwdoV{e2mwZzDU[YwuXHmtMjDrbY5ie2ViYX\0[ZIhPDhiaILzJIJ6KE2WUzDhd5NigSxiR1m1NEA:KDJizszNMi=>	NU\PSIlZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxN\|gzPDZpPkKxNVM5OjR4PD;hQi=>
BA/F3	NVq4WpgxT3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=		MofoOFghcHK\|		M1vYOmdzd3e2aDDpcohq[mm2aX;uJI9nKG2xdYPlJGJCN0Z\|IHPlcIx{KGW6cILld5NqdmdiVHXsMWpCUzNia3nuZZNmKGGodHXyJFQ5KGi{czDifUBOXFNiYYPzZZktKEeLNUCgQUAzNjFizszNMi=>	M3z2c\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
UKE1	MkXpSpVv[3Srb36gZZN{[Xl?		NVj2TWhJOSCqch?=		MUHJcohq[mm2aX;uJI9nKFO2YYS1JJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDVT2UyKGOnbHzzJIFnfGW{IEGgbJIh[nliV3XzeIVzdiCkbH;0eIlv\w>?	NGnhcI49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUGzPFI1Pid-MkGxN\|gzPDZ:L3G+
SW620	M4HxRWNmdGxiY4njcIUh[XO\|YYm=	NUiydodDOy5\|IIXN	MWeyOEBpenN?		M{n0R2NmdGxiY4njcIUh[XK{ZYP0JIlvKGi3bXHuJHNYPjJyIHPlcIx{KGG\|c3Xzd4VlKGG\|IHHjZ5VufWyjdHnvckBifCCJMj;NJJBp[XOnIHH0JFMvOyC3TTDh[pRmeiB{NDDodpMh[nliZnzve{BkgXSxbXX0dpk>	Mn\WQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzM{iyOFYoRjJzMUO4NlQ3RC:jPh?=
HEL	M{Pne2Z2dmO2aX;uJIF{e2G7	NFHoR2kxNjNidV2=	MWi1JI1qdnN?		M3PRNWlvcGmkaYTpc44hd2ZiU4TheFUheGixc4Doc5J6dGG2aX;uJIlvKGi3bXHuJGhGVCClZXzsd{BifCByLkOgeW0h[W[2ZYKgOUBucW6\|IHL5JHdme3Sncn6gZoxwfHSrbne=	NGnnSVg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUGzPFI1Pid-MkGxN\|gzPDZ:L3G+
HEL	NV7JZll{TnWwY4Tpc44h[XO\|YYm=	NYLkXZlTOC5\|IIXN	NXHhUm81OzBidH:gOlAhdWmwcx?=		MYrJcohq[mm2aX;uJI9nKFO2YYS1JJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDISWwh[2WubIOgZZQhOC5\|IIXNJIFnfGW{IEOwJJRwKDZyIH3pcpMh[nliV3XzeIVzdiCkbH;0eIlv\w>?	MnzOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzM{iyOFYoRjJzMUO4NlQ3RC:jPh?=
BA/F3	NFXUSW9CdnSrdIXtc5Ih[XO\|YYm=	MlG1N\|AhdWdxa3e=	M4HydFEzKGi{cx?=		MomzRY51cXS3bX;yJIFkfGm4aYT5JIFo[Wmwc4SgcY92e2ViQlGvSlMh[2WubIOg[ZhxemW\|c3nu[{BV\WxvSlHLNkB5\W6xZ4Lh[pRm\CCrbjDOR5IhdW:3c3WgZZN{\XO\|ZXSgZZMhemWmdXP0bY9vKG:oIIDoc5NxcG:{eXzheIVlKFO2YYS1JIxmfmWuIHnuJJNxdGWnbjDheEA{OCCvZz;r[{wheG9iYX\0[ZIhOTJiaILzJIJ6KFenc4Tldo4h[myxdITpcoc>	MofyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzM{iyOFYoRjJzMUO4NlQ3RC:jPh?=
HEL	MX;GeY5kfGmxbjDhd5NigQ>?	MkHmNE4{KHWP	MnS0OUBucW6\|		MV;Jcohq[mm2aX;uJI9nKFO2YYSzJJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDISWwh[2WubIOgZZQhOC5\|IIXNJIFnfGW{IEWgcYlveyCkeTDX[ZN1\XKwIHLsc5R1cW6p	M3;lSlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
HEL	NF;abJFHfW6ldHnvckBie3OjeR?=	NEiy[FAxNjNidV2=	MnrxN\|AhfG9iNkCgcYlvew>?		M17le2lvcGmkaYTpc44hd2ZiU4TheFMheGixc4Doc5J6dGG2aX;uJIlvKGi3bXHuJGhGVCClZXzsd{BifCByLkOgeW0h[W[2ZYKgN\|AhfG9iNkCgcYlveyCkeTDX[ZN1\XKwIHLsc5R1cW6p	NWXKfmFkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxN\|gzPDZpPkKxNVM5OjR4PD;hQi=>
Hs578T	MWLGeY5kfGmxbjDhd5NigQ>?	MoHPNUB2VQ>?	M2TVdlI1KGi{cx?=		NF;iNIxKdmirYnn0bY9vKG:oIGPURXQ{Sy2vZXTpZZRm\CC2cnHud4NzcXC2aX;uJIlvKGi3bXHuJGh{PTd6VDDj[YxteyCjdDCxJJVOKGGodHXyJFI1KGi{czDifUBtfWOrZnXyZZNmKHKncH;yeIVzKGenbnWgZZN{[Xl?	NFXjTpc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEm3PFEyOid-MkS5O\|gyOTJ:L3G+
NCI-H1975	NUfBPWl7TnWwY4Tpc44h[XO\|YYm=	NH;Ic2oxNjByMzD0c{A{KHWP	Mmr4NkBpenN?		NEfvTXpKdmirYnn0bY9vKG:oIFrBT\|EhcW5iaIXtZY4hVkOLLVixPVc2KGOnbHzzJIF{e2W\|c3XkJIF{KHKnZIXjeIlwdiCrbjDTWGFVOyCyaH;zdIhwenmuYYTpc44h[XRiMD6wNFMhfG9iMzD1UUBi\nSncjCyJIhzeyCkeTDX[ZN1\XKwIHLsc5Qh[W6jbInzbZM>	Mk\aQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ4MUS0NFgoRjJ4NkG0OFA5RC:jPh?=
HEL 92.1.7	NYK5fZB[TnWwY4Tpc44h[XO\|YYm=		MoO1NkBpenN?		NV35Rog3UW6qaXLpeIlwdiCxZjDKRWszKGmwIHj1cYFvKEiHTDC5Nk4yNjdiY3XscJMh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJHNVSVR3IIDoc5NxcG:{eXzheIlwdiCjZoTldkAzKGi{czDifUBY\XO2ZYLuJIJtd3RiYX7hcJl{cXN?	M1vmTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NkG0OFA5Lz5{Nk[xOFQxQDxxYU6=
DAOY	NGLVbVdyUFSVIHHzd4F6				M4jaOJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCGQV;ZJINmdGy\|	NX:zcY5iRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
SJ-GBM2	NH3EVVFyUFSVIHHzd4F6				MnLLdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFOMLVfCUVIh[2WubIO=	M3\IRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
A673	MlPZdWhVWyCjc4PhfS=>				M13WfZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCDNkezJINmdGy\|	MnrNQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SK-N-MC	NF3oSXpyUFSVIHHzd4F6				M3;MdZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMW1EKGOnbHzz	NEC1Roo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
BT-37	MX;xTHRUKGG\|c3H5				MkiydWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUO3JINmdGy\|	M{jqVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
NB-EBc1	NIDqcmtyUFSVIHHzd4F6				M4nydpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCQQj3FRoMyKGOnbHzz	NFr0[\|k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
Saos-2	MWnxTHRUKGG\|c3H5				NGDV[FVyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU3Hvd{0zKGOnbHzz	MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-SH	NX;WUIhzeUiWUzDhd5NigQ>?				M2TwXZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSz3OMXNJKGOnbHzz	NIHkUng9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
NB1643	M1y3WZFJXFNiYYPzZZk>				M2PkWZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCQQkG2OFMh[2WubIO=	NXrNbXdHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
BT-12	MVHxTHRUKGG\|c3H5				MVfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSlRvMUKgZ4VtdHN?	M2\hO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
OHS-50	MX7xTHRUKGG\|c3H5				M{npfJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCRSGOtOVAh[2WubIO=	NIL2S2Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
RD	NELzd\|ByUFSVIHHzd4F6				M1nPTZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCURDDj[Yxtew>?	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
MG 63 (6-TG R)	Ml\PdWhVWyCjc4PhfS=>				M3zC[5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCPRzC2N{ApPi2WRzDSLUBk\Wyucx?=	NFW4XZk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
Rh41	NWC5[VhUeUiWUzDhd5NigQ>?				NWPHTGJ4eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLoOFEh[2WubIO=	NXXpUm9ORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>

... 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

体内研究

AZD1480作用于人类实体瘤模型和多发性骨髓瘤模型，抑制 STAT3磷酸化。^[1]在体内, AZD1480抑制皮下移植瘤的生长，且通过抑制STAT3活性提高携带颅内恶性胶质瘤(GBM)的鼠寿命，说明AZD1480抑制JAK/STAT3通路的药理学可以用于研究治疗携带颅内恶性胶质瘤的患者。^[3]AZD1480抑制骨髓细胞的肺浸润和肺转移瘤。AZD1480作用于人类移植瘤模型降低血管生成和代谢。^[4]AZD1480抑制含有STAT活性的人类实体瘤的生长。^[5]

激酶实验：^[5]	- 合并激酶实验: 在有buffer(包括50 mM HEPES pH 为7.3, 1 mM DTT, 0.01% Tween-20, 50 µg/ml BSA,及10 mM MgCl₂)的条件下，使用重组Jak1, Jak2, 或Jak3进行AZD1480抑制效果研究。在昆虫细胞中，Jak3酶表达为氮端GST融合蛋白，且通过谷胱甘肽亲和及尺寸排除色谱来纯化Jak3酶。加入AZD1480 (10点剂量反应, 重复三次, 8.3 µM 到0.3 nM )，使用1.5 µM 肽底物(Jak1:FITC-C6-KKHTDDGYMPMSPGVA-NH2, Jak2和Jak3: FAM-SRCtide)，及各自ATP K_m (Jak1: 55 µM, Jak2: 15 µM, Jak3: 3 µM)，ATP浓度为5 mM，进行酶实验。分离磷酸化和未磷酸化的肽段，使用Caliper LC3000系统计算抑制百分率。
细胞实验：^[4]	- 合并 Cell lines: Renca或786-O细胞，鼠内皮细胞和脾CD11b+/c−骨髓细胞, HUVECs Concentrations: 1 μM Incubation Time: 48或24小时 Method: Renca或786-O细胞悬浮在含5%FBS的DMEM培养基中,按每孔5×10³个细胞接种在96孔板上，使细胞粘附，实验组用AZD1480，对照组用DMSO，处理48小时。通过MTS实验测定细胞活力。使用Mikrotek Laborsysteme在490nm处测定吸光值。鼠内皮细胞和脾CD11b+/c− 骨髓细胞从携带肿瘤的鼠中富集得到，培养在含5% FBS的RPMI-1640培养基上。HUVECs 培养在胶原1包被的含完全培养基的板上。用DMSO和不同剂量AZD1480处理所有细胞，持续24小时。手动计算细胞数而测定细胞活力。所有实验重复三次。 (Only for Reference)
动物实验：^[4]	- 合并 Animal Models: 雌性BALB/c和无胸腺鼠(NCR− nu/nu) (7-8周大) Dosages: 每天一次，剂量为50 mg/kg；或者每天两次，剂量为30 mg/kg Administration: 口服饲喂 (Only for Reference)

参考文献

- 合并

溶解度 (25°C)

体外	DMSO	69 mg/mL warmed (197.83 mM)
	Water	Insoluble
	Ethanol	Insoluble
体内	从左到右依次将纯溶剂加入产品，现配现用(数据来自Selleck实验检测而非文献)： 30% PEG400+0.5% Tween80+5% propylene glycol	5 mg/mL

* 溶解度检测是由Selleck技术部门检测的，可能会和文献中提供的溶解度有所差异，这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据 Download AZD1480 SDF

分子量	348.77
化学式	C₁₄H₁₄ClFN₈
CAS号	935666-88-9
储存条件	3年-20°C 粉状 2年-80°C 溶于溶剂
别名	N/A

动物体内配方计算器 (澄清溶液)

第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）

给药剂量

mg/kg

动物平均体重

每只动物给药体积

动物数量

只

第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）

% DMSO+ % + % Tween 80+ % ddH₂O

计算重置

计算结果:

工作液浓度： mg/ml；

DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；

体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH₂O，混匀澄清。

注意：1. 首先保证母液是澄清的；
2. 一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。

计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

质量

浓度

体积

分子量
=

×

×

*在配置溶液时，请务必参考Selleck产品标签上、SDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。

稀释计算器

用本工具协助配置特定浓度的溶液，使用的计算公式为：

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入输出 )

C1

V1

C2

V2
×

=

×

在配置溶液时，请务必参考Selleck产品标签上、SDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。.

连续稀释计算器方程

连续稀释
初始浓度:
稀释倍数:

计算结果

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):

分子量计算器

通过输入化合物的化学式来计算其分子量：

注：化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量	浓度	体积	分子量
=	×	×
计算

临床试验信息 (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

技术支持

在订购、运输、储存和使用我们的产品的任何阶段，您遇到的任何问题，均可以通过拨打我们的热线电话400-668-6834，或者技术支持邮箱tech@selleck.cn，直接联系到我们。我们会在24小时内尽快联系您。

操作手册

如果有其他问题，请给我们留言。

JAK Signaling Pathway Map

JAK Inhibitors with Unique Features

泛JAK抑制剂

Ruxolitinib (INCB018424) : Pan JAK1/2 inhibitor, IC50=3.3 nM/2.8 nM.
FDA批准的JAK抑制剂

Tofacitinib (CP-690550,Tasocitinib) : Approved by FDA for rheumatoid arthritis (RA).
最新的JAK抑制剂

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

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.

研究领域

产品类型

定制您的化合物库

AZD1480

客户使用Selleck生产的AZD1480发表文献91篇：

产品安全说明书

JAK抑制剂选择性比较

生物活性

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

参考文献

溶解度 (25°C)

化学数据 Download AZD1480 SDF

动物体内配方计算器 (澄清溶液)

计算器

摩尔浓度计算器

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

稀释计算器

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

连续稀释计算器方程

连续稀释

计算结果

分子量计算器

总分子量：g/mol

摩尔浓度计算器

临床试验信息 (data from https://clinicaltrials.gov, updated on 2021-09-06)

技术支持

JAK Signaling Pathway Map

JAK Inhibitors with Unique Features

相关JAK产品