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分装免费

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98篇：

Immunity, 2021, 54(11):2514-2530.e7

PubMed: 34717796 ( click the link to review the publication )

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 )

Mol Neurodegener, 2022, 17(1):7

PubMed: 35012605 ( click the link to review the publication )

Sci Rep, 2022, 12(1):7

PubMed: 34997030 ( 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 )

Front Immunol, 2021, 12:712781

PubMed: 34594328 ( click the link to review the publication )

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

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

Lab Invest, 2021, 10.1038/s41374-021-00703-5

PubMed: 34789838 ( click the link to review the publication )

Front Mol Biosci, 2021, 8:652443

PubMed: 34746227 ( 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, 11(8):1208-19

PubMed: 26004178 ( 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	M3L5R2Z2dmO2aX;uJGF{e2G7	NEnye\|g2KM7:TR?=	NVnMcmU6PDhiaB?=	M{\IPGROW09?	M4T2WIJtd2OtczDKRWszN1OWQWSzJJNq\26jbHnu[y=>	NF;MdlY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUm1OFk4PCd-MkW5OVQ6PzR:L3G+
LoVo	NU\yW20xTnWwY4Tpc44hSXO\|YYm=	MW[1JO69VQ>?	Ml7nOFghcA>?	MXTEUXNQ	MVXicI9kc3NiSlHLNk9UXEGWMzDzbYdv[Wyrbne=	M324XlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OUW0PVc1Lz5{NUm1OFk4PDxxYU6=
HN5	M3\veWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		NFPBOmQ4OiCq		NXzVRlVDTUN3ME2zMlgyKMLzIEGuPVkh\|ryP	M{DMSVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEGwNFExLz5{NUixNFAyODxxYU6=
Cal33	M1LIXGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		MneyO\|IhcA>?		MUHFR\|UxRTNwM{egxtEhOC55NTFOwG0>	MlzPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6MUCwNVAoRjJ3OEGwNFExRC:jPh?=
UM-22B	NWj3cllCT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		NFzzZ3E4OiCq		NUDWWJhxTUN3ME2yMlY3KMLzIECuNlQh\|ryP	MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPThzMECxNEc,OjV6MUCwNVA9N2F-
686LN	NGPVcZpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		MXG3NkBp		M2n4VWVEPTB;Mj6wOUDDuSBzLkOzJO69VQ>?	M1;mflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEGwNFExLz5{NUixNFAyODxxYU6=
UM SCC-1	M4j1Zmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		NYH6codQPzJiaB?=		NIKwVHBGSzVyPUGuOlchyrFiMD60NkDPxE1?	MlTMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6MUCwNVAoRjJ3OEGwNFExRC:jPh?=
UM-22A	MnfQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		M3LFXVczKGh?		NVH5d4FRTUN3ME2xMlMzKMLzIECuN\|kh\|ryP	Mn7sQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6MUCwNVAoRjJ3OEGwNFExRC:jPh?=
OSC19	MoPuS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		NESycnQ4OiCq		MYPFR\|UxRTFwMk[gxtEhOC5{MDFOwG0>	NVXUZWVyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NVAxOTBpPkK1PFExODFyPD;hQi=>
PCI-52	NGXKOWpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		MonRO\|IhcA>?		M1jEWGVEPTB;MT6wNEDDuSByLkC5JO69VQ>?	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPThzMECxNEc,OjV6MUCwNVA9N2F-
PCI-15B	NXfseGpkT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		NV;6ZmpQPzJiaB?=		MVrFR\|UxRTBwOUmgxtEhOS55NDFOwG0>	MnfTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6MUCwNVAoRjJ3OEGwNFExRC:jPh?=
UMSCC-1	M3nTTGZ2dmO2aX;uJGF{e2G7	NGD2[HExNjByMEWtNU43KM7:TR?=	Mli0NlQhcA>?		Mk\XZYJzd2ejdHXzJGlNNTckgKPpcoR2[2WmIIXwMZJm\3WuYYTpc44hd2ZicGPURXQ{XHm{N{C1xsBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=>	MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPThzMECxNEc,OjV6MUCwNVA9N2F-
Cal33	NUKwRlcyTnWwY4Tpc44hSXO\|YYm=	M3zHNlAvODByNT2zMlgh\|ryP	M3HmTVI1KGh?		NWHveIY1[WK{b3fheIV{KEmOLUdihLNqdmS3Y3XkJJVxNXKnZ4XsZZRqd25ib3[gdHNVSVR\|VInyO\|A2yqCrbjDhJIRwe2VvZHXw[Y5l\W62IH3hco5meg>?	NWLaXIgyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NVAxOTBpPkK1PFExODFyPD;hQi=>
HH5	MkLNSpVv[3Srb36gRZN{[Xl?	M3z1bVAvODByNT2zMlgh\|ryP	NVf4UllpOjRiaB?=		M37GVYFjem:pYYTld{BKVC144pETbY5lfWOnZDD1dE1z\We3bHH0bY9vKG:oIIDTWGFVO1S7ckewOeKhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>	NGTnSoE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUixNFAyOCd-MkW4NVAxOTB:L3G+
UM-22A	M331UWZ2dmO2aX;uJGF{e2G7	Mm\NNE4xODB3LUGuOkDPxE1?	MVKyOEBp		M1PSToFjem:pYYTld{BKVC144pETbY5lfWOnZDD1dE1z\We3bHH0bY9vKG:oIIDTWGFVO1S7ckewOeKhcW5iYTDkc5NmNWSncHXu[IVvfCCvYX7u[ZI>	M13iUlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEGwNFExLz5{NUixNFAyODxxYU6=
A1847	MmS1SpVv[3Srb36gRZN{[Xl?	NWKxU3dbOC5yNT2xNEDPxE1?	MUmyOEBp	MV;EUXNQyqB?	NFT6dXNz\WS3Y3XzJJBpd3OyaH;yfYxifGWmIGPURXQ{KGyndnXsdy=>	M2rN[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkS2NFE2Lz5{NU[0OlAyPTxxYU6=
OVCAR-5	MljVSpVv[3Srb36gRZN{[Xl?	MXmwMlA2NTFyIN88US=>	NFTpPIszPCCq	NIXHfnpFVVORwrC=	NFL1fJZz\WS3Y3XzJJBpd3OyaH;yfYxifGWmIGPURXQ{KGyndnXsdy=>	NELtRYU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[0OlAyPSd-MkW2OFYxOTV:L3G+
OVCAR-8	NVLxRZRZTnWwY4Tpc44hSXO\|YYm=	NHj3PHMxNjB3LUGwJO69VQ>?	NHfBS2gzPCCq	NYfoeIJjTE2VT9Mg	M3XW[5Jm\HWlZYOgdIhwe3Cqb4L5cIF1\WRiU2TBWFMhdGW4ZXzz	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ2NkCxOUc,OjV4NE[wNVU9N2F-
MOVCAR-5447	M1;3XGZ2dmO2aX;uJGF{e2G7	MWiwMlA2NTFyIN88US=>	Ml:1NlQhcA>?	NXLqfnE3TE2VT9Mg	NVTRVYUxemWmdXPld{BxcG:\|cHjvdplt[XSnZDDTWGFVOyCuZY\lcJM>	NIjNWI49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[0OlAyPSd-MkW2OFYxOTV:L3G+
MOVCAR-5009	M4TXcGZ2dmO2aX;uJGF{e2G7	M4\SWFAvODVvMUCg{txO	NIPLb4QzPCCq	MV3EUXNQyqB?	MYXy[YR2[2W\|IIDoc5NxcG:{eXzheIVlKFOWQWSzJIxmfmWucx?=	M{jPT\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkS2NFE2Lz5{NU[0OlAyPTxxYU6=
A1847	MVnD[YxtKF[rYXLpcIl1gSCDc4PhfS=>	NHzFUFcxNjB3LUGwJO69VQ>?	NF\KRlk4OiCq	M{\SNWROW09?	MVny[YR2[2W\|IHPlcIwhfmmjYnnsbZR6KGG2IITo[UBkd26lZYLueJJifGmxbjDv[kA2KM7:TR?=	NHzw[2w9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[0OlAyPSd-MkW2OFYxOTV:L3G+
OVCAR-5	NXnEVpg2S2WubDDWbYFjcWyrdImgRZN{[Xl?	NEe1ZWgxNjB3LUGwJO69VQ>?	NEfGXXQ4OiCq	NW\HOXEyTE2VTx?=	Moq2doVlfWOnczDj[YxtKH[rYXLpcIl1gSCjdDD0bIUh[2:wY3XycpRz[XSrb36gc4YhPSEQvF2=	M4q5bVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkS2NFE2Lz5{NU[0OlAyPTxxYU6=
OVCAR-8	NUTFbmtiS2WubDDWbYFjcWyrdImgRZN{[Xl?	NH7ZZoYxNjB3LUGwJO69VQ>?	MXW3NkBp	NGrOc2hFVVOR	M1;UOZJm\HWlZYOgZ4VtdCC4aXHibYxqfHliYYSgeIhmKGOxbnPldo51emG2aX;uJI9nKDVizszN	M1XBPFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkS2NFE2Lz5{NU[0OlAyPTxxYU6=
OVCAR-5	NVryW4xOSXCxcITvd4l{KEG\|c3H5	NIjSRm8xNjVxMT:1JO69VQ>?	Mmf3OFghcA>?	M1izVGROW09?	NHfqS4VqdmS3Y3XzJJNq\26rZnnjZY51KGGyb4D0c5NqeyCjdDDobYdpKGOxbnPldo51emG2aX;u	NFLzbHA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[0OlAyPSd-MkW2OFYxOTV:L3G+
OVCAR-8	Mmn5RZBweHSxc3nzJGF{e2G7	NXfyTnBWOC53L{GvOUDPxE1?	NISxco01QCCq	MljqSG1UVw>?	NW\0NnVNcW6mdXPld{B{cWewaX\pZ4FvfCCjcH;weI9{cXNiYYSgbIlocCClb37j[ZJvfHKjdHnvci=>	M1ewS\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkS2NFE2Lz5{NU[0OlAyPTxxYU6=
AKRSL	MYHD[YxtKF[rYXLpcIl1gSCDc4PhfS=>		NV33[pd7PzJiaB?=		NUKzU\|N7UUN3MP-8olExKM7:TR?=	NEKxeGo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUWwOFY{PSd-MkW1NFQ3OzV:L3G+
PALJDL	NUDuTFJmS2WubDDWbYFjcWyrdImgRZN{[Xl?		NHv2fWM4OiCq		Mm\3TWM2OD1{LkSg{txO	NVfXWlhlRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW1NFQ3OzVpPkK1OVA1PjN3PD;hQi=>
MO4	NWPiZ4FCTnWwY4Tpc44hSXO\|YYm=	MXmwMlUwOS93IN88US=>	NXPqOIFTPiCq		MkHTbY5pcWKrdIOgVE1UXEGWMzDlfJBz\XO\|aX;uxsA>	M3mxWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MUS5OVM2Lz5{NUG0PVU{PTxxYU6=
DU145	M1X2OWZ2dmO2aX;uJGF{e2G7	NU\HdlNCOC1{MECgcm0>	NXTYXpVYOSCqwrC=		NGfXc3J{fXCycnXzd4V{KEmOLU[tZYN1cX[jdHXkJHN1[XR\|IHHu[EBGWktzL{Kgd4lodmGuaX7n	M1nzS\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2NUe3PVQzLz5{NEW3O\|k1OjxxYU6=
DU145	MYfGeY5kfGmxbjDBd5NigQ>?	M{L3dVgxOCCwTR?=	M4rGNFczKGh?		NX7vPGN[e3WycILld5NmeyCLTD22MYlv\HWlZXSgcYloemG2b4L5	MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDV5N{m0Nkc,OjR3N{e5OFI9N2F-
CWR22Rv1	NELLSI1HfW6ldHnvckBCe3OjeR?=	NHTuTnA5ODBibl2=	NVX4VlJmPzJiaB?=		Mk\Id5VxeHKnc4Pld{BKVC14LXnu[JVk\WRibXnndoF1d3K7	NY\MWGdRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS1O\|c6PDJpPkK0OVc4QTR{PD;hQi=>
N592	MkG4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				NEXReHdKSzVyPUCuPFQh\|ryP	NF3VRnM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEG1PFcxOSd-MkSxOVg4ODF:L3G+
H82	NX;sR\|hGT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=				NXvUSYFwUUN3ME2xMlM4KM7:TR?=	Mn\wQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzNUi3NFEoRjJ2MUW4O\|AyRC:jPh?=
GLC4	Mmj2S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				NH32dllKSzVyPUGuO\|kh\|ryP	MnO4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzNUi3NFEoRjJ2MUW4O\|AyRC:jPh?=
H526	NUewdpc3T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=				NHnxbZVKSzVyPUOuNFgh\|ryP	MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF3OEewNUc,OjRzNUi3NFE9N2F-
H1173	MlTPS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?				NWrvToh1UUN3ME2yMlM6KM7:TR?=	M4D2[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MUW4O\|AyLz5{NEG1PFcxOTxxYU6=
DMS114	NVj5VIN2T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=				M{nvSGlEPTB;MD63N{DPxE1?	NHjNSFU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEG1PFcxOSd-MkSxOVg4ODF:L3G+
NCI-N592	MnrPSpVv[3Srb36gRZN{[Xl?	NGm3OoUxNjNxMT:zJO69VQ>?	MljPNlQhcA>?		M4e0UIlv\HWlZYOgS\|IwVSClZXzsJIN6[2ynIHHydoV{fA>?	NVLJ[XVERGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSxOVg4ODFpPkK0NVU5PzBzPD;hQi=>
GLC4	NIXkbGlHfW6ldHnvckBCe3OjeR?=	NFnDOo4xNjNxMT:zJO69VQ>?	NVXJVm9GOjRiaB?=		M{Cwc4lv\HWlZYOgS\|IwVSClZXzsJIN6[2ynIHHydoV{fA>?	Mkm4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzNUi3NFEoRjJ2MUW4O\|AyRC:jPh?=
NCI-H82	M1XVSGZ2dmO2aX;uJGF{e2G7	M1vOOFAvOy9zL{Og{txO	MYKyOEBp		NYPSbZRwcW6mdXPld{BIOi:PIHPlcIwh[3mlbHWgZZJz\XO2	NFu2XVM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEG1PFcxOSd-MkSxOVg4ODF:L3G+
NCI-N592	MlLxRZBweHSxc3nzJGF{e2G7	NIH5NoMxNjNxMT:zJO69VQ>?	MWi0PEBp		MoLmbY5kemWjc3XzJJRp\SCuZY\lcEBw\iClbHXheoVlNUOjc4Dhd4UhOw>?	NHXQR4E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEG1PFcxOSd-MkSxOVg4ODF:L3G+
GLC4	M1X2[mFxd3C2b4Ppd{BCe3OjeR?=	M4jjOFAvOy9zL{Og{txO	NWTFRphWPDhiaB?=		MX7pcoNz\WG\|ZYOgeIhmKGyndnXsJI9nKGOuZXH2[YQuS2G\|cHHz[UA{	MoeyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzNUi3NFEoRjJ2MUW4O\|AyRC:jPh?=
NCI-H82	NETYfHpCeG:ydH;zbZMhSXO\|YYm=	NYHVboJjOC5\|L{GvN{DPxE1?	NWTIV3g4PDhiaB?=		MUnpcoNz\WG\|ZYOgeIhmKGyndnXsJI9nKGOuZXH2[YQuS2G\|cHHz[UA{	NEX5bVQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEG1PFcxOSd-MkSxOVg4ODF:L3G+
CWR22Rv1	NI\HW2RCeG:ydH;zbZMhSXO\|YYm=				MnTyTWM2OD1yLkS4NkDPxE1?	NETt[5k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{m0NlA6PSd-MkO5OFIxQTV:L3G+
CWR22Pc	M4PSN2Fxd3C2b4Ppd{BCe3OjeR?=				M4LubmlEPTB;MD60N\|gh\|ryP	NVP1boFMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5OFIxQTVpPkKzPVQzODl3PD;hQi=>
PC-3	NEHa[49CeG:ydH;zbZMhSXO\|YYm=				Mm\lTWM2OD1zLke1OUDPxE1?	NX\tNWw{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5OFIxQTVpPkKzPVQzODl3PD;hQi=>
DU145	NHe2SJpCeG:ydH;zbZMhSXO\|YYm=				MnfwTWM2OD1\|LkWxO{DPxE1?	MoezQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN7NEKwPVUoRjJ\|OUSyNFk2RC:jPh?=
RC165N	NU\sdFI{SXCxcITvd4l{KEG\|c3H5				MVPJR\|UxRTJwMEizJO69VQ>?	NV7WVWxCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO5OFIxQTVpPkKzPVQzODl3PD;hQi=>
ARPE19	MljIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NIrBTVlFVVOR	M1vEdGlEPTB;MkSuN\|gh\|ryP	Mnz5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ\|NUOxPVIyRC:jPh?=
HEK293	NGXCZYtIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MX7EUXNQ	NHv4TXZKSzVyPUiuOlch\|ryP	NXTMXGRoRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
KCNR	MoraS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			NXnyOnAyTE2VTx?=	NFnZUJBKSzVyPUCuOFYh\|ryP	MVm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
SY5Y	NUDKUlllT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			MnPlSG1UVw>?	MkLaTWM2OD1yLkO2JO69VQ>?	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
BE2	NHHHSo1Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MlPXSG1UVw>?	NW\YOoR2UUN3ME2wMlcyKM7:TR?=	MmLXQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ\|NUOxPVIyRC:jPh?=
AS	M1jacWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			Mn7KSG1UVw>?	MVjJR\|UxRTFwNUOg{txO	M1qxSlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NUOxPVIyLz5{M{WzNVkzOTxxYU6=
NGP	MoHTS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?			MojGSG1UVw>?	MoS2TWM2OD1yLkW2JO69VQ>?	NFrMd2E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N\|E6OjF:L3G+
IMR32	M{SweWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NYDmR\|R4TE2VTx?=	MmDCTWM2OD1yLk[2JO69VQ>?	MlS5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ\|NUOxPVIyRC:jPh?=
LAN5	M1\PVmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NGnN[GpFVVOR	NWnoPYxwUUN3ME2xMlA1KM7:TR?=	NWLO[4JjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
RH18	NFTHWXlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			MVHEUXNQ	NHXxPWhKSzVyPUGuOFIh\|ryP	MYG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
RH30	NIHqU\|ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NUjuR4R5TE2VTx?=	M{juPGlEPTB;MT6yOUDPxE1?	MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
RH17	M3LvZmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			MnfuSG1UVw>?	NV6zXoM4UUN3ME2yMlUyKM7:TR?=	NFf3U\|c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N\|E6OjF:L3G+
RH28	MVfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?			NEfwfIJFVVOR	NYfQb\|dQUUN3ME20MlI5KM7:TR?=	NI\5TmE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N\|E6OjF:L3G+
RH36	NELqOJBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=			NYrCNpczTE2VTx?=	MYnJR\|UxRTVwM{eg{txO	MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
RH41	M2DDcmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NXe2W2xZTE2VTx?=	NVf3dWU4UUN3ME2wMlQ5KM7:TR?=	NH;KU5c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N\|E6OjF:L3G+
RD	NYnGUJpOT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			MlrnSG1UVw>?	Ml3YTWM2OD12LkOyJO69VQ>?	NF\OdGw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N\|E6OjF:L3G+
TC32	M{HhcGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7			NVfldXdsTE2VTx?=	NXv6W2pKUUN3ME2zMlg2KM7:TR?=	MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
TC71	NYK1Z25pT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=			Mm\4SG1UVw>?	M3;V[GlEPTB;ND6zN{DPxE1?	MlPpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ\|NUOxPVIyRC:jPh?=
KCNR	M3;pT2Fxd3C2b4Ppd{BCe3OjeR?=	MljENE42NzFwMD:yMlUh\|ryP	NEntSJYzPCCq	M3\hTmROW09?	MnzLbY5lfWOnczDhckBqdmO{ZXHz[UBqdiClYYPwZZNmKDNxNzDhZ5Rqfmm2eR?=	NYK3PVZnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N\|E6OjFpPkKzOVMyQTJzPD;hQi=>
SY5Y	M1zHdGFxd3C2b4Ppd{BCe3OjeR?=	MYOwMlUwOS5yL{KuOUDPxE1?	NVnHWmdbOjRiaB?=	NXT4TpFtTE2VTx?=	MYHpcoR2[2W\|IHHuJIlv[3KnYYPlJIlvKGOjc4Dhd4UhOy95IHHjeIl3cXS7	MoXOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ\|NUOxPVIyRC:jPh?=
Rh18	M3jPUWFxd3C2b4Ppd{BCe3OjeR?=	MnvMNE42NzFwMD:yMlUh\|ryP	NV70PVVyOjRiaB?=	NVPGSplRTE2VTx?=	M3HzT4lv\HWlZYOgZY4hcW6lcnXhd4UhcW5iY3HzdIF{\SB\|L{egZYN1cX[rdIm=	NGnVZ\|I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N\|E6OjF:L3G+
TC32	NULYU\|BqSXCxcITvd4l{KEG\|c3H5	NFi2bVQxNjVxMT6wM\|IvPSEQvF2=	Ml;XNlQhcA>?	NYfaSXc{TE2VTx?=	M170ZYlv\HWlZYOgZY4hcW6lcnXhd4UhcW5iY3HzdIF{\SB\|L{egZYN1cX[rdIm=	MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV\|MUmyNUc,OjN3M{G5NlE9N2F-
KCNR	MVHGeY5kfGmxbjDBd5NigQ>?	M1m0R\|AvPS9zLkCvNk42NzVizszN	MV2yOEBp	MY\EUXNQ	MkG0bY5pcWKrdIOgZo91cCCnbnTv[4Vvd3W\|IHPvcpN1cXS3dHn2[UBidmRiSVytOk1qdmS3Y3XkJHNVSVR\|IHHjeIl3[XSrb36=	Mke1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ\|NUOxPVIyRC:jPh?=
SY5Y	M4LuTmZ2dmO2aX;uJGF{e2G7	NH3OUJQxNjVxMT6wM\|IvPS93IN88US=>	Mk\SNlQhcA>?	Mm\KSG1UVw>?	NFr0XW9qdmirYnn0d{Bjd3SqIHXu[I9o\W6xdYOgZ49ve3SrdIX0bZZmKGGwZDDJUE03NWmwZIXj[YQhW1SDVEOgZYN1cX[jdHnvci=>	NFnzVm89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N\|E6OjF:L3G+
Rh18	NEDQdnZHfW6ldHnvckBCe3OjeR?=	MViwMlUwOS5yL{KuOU82KM7:TR?=	MofwNlQhcA>?	Ml\nSG1UVw>?	M1rMNolvcGmkaYTzJIJwfGhiZX7kc4dmdm:3czDjc45{fGm2dYTpeoUh[W6mIFnMMVYucW6mdXPl[EBUXEGWMzDhZ5RqfmG2aX;u	MorIQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ\|NUOxPVIyRC:jPh?=
TC32	MUDGeY5kfGmxbjDBd5NigQ>?	Mn;PNE42NzFwMD:yMlUwPSEQvF2=	NIjieWgzPCCq	NFTkTGtFVVOR	NIfFZ\|FqdmirYnn0d{Bjd3SqIHXu[I9o\W6xdYOgZ49ve3SrdIX0bZZmKGGwZDDJUE03NWmwZIXj[YQhW1SDVEOgZYN1cX[jdHnvci=>	MoHxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ\|NUOxPVIyRC:jPh?=
TPC-1	M1PzO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MVWxJOK2VQ>?	NXi1Z2ZbOC12IHS=	NF;TZVVFVVOR	NEDV[ohqdmirYnn0d{Bk\WyuIHfyc5d1cCCjZoTldkAzKGRidILlZZRu\W62	MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzB3NkS5PUc,OjNyNU[0PVk9N2F-
MZ-CRC1	MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	M3jJelEhyrWP	Mn;xNE02KGR?	NYC1OmtOTE2VTx?=	M3\yeolvcGmkaYTzJINmdGxiZ4Lve5RpKGGodHXyJFEh\CC2cnXheI1mdnR?	NXnrcnVjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOwOVY1QTlpPkKzNFU3PDl7PD;hQi=>
TT	NV3NTpRUT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	NXXkPJY6OSEEtV2=	NHH0cmIxNTRiZB?=	NYLLNGxDTE2VTx?=	NFv3flhqdmirYnn0d{Bk\WyuIHfyc5d1cCCjZoTldkAyKGRidILlZZRu\W62	M1;w[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|MEW2OFk6Lz5{M{C1OlQ6QTxxYU6=
TPC-1	NVLtVohNTnWwY4Tpc44hSXO\|YYm=	M1fyflEhyrWP	NV7rVFgxPzJiaB?=	NUXKVW1[TE2VTx?=	M{TLTolv\HWlZYOgS\|Eh[myxY3vh[4U>	NUX0UXhwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOwOVY1QTlpPkKzNFU3PDl7PD;hQi=>
MZ-CRC1	MYTGeY5kfGmxbjDBd5NigQ>?	NX:3UZB4OSEEtV2=	MV63NkBp	MUnEUXNQ	NH\vNY5qdmS3Y3XzJGcyKGKub3PrZYdm	NYX2fowxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOwOVY1QTlpPkKzNFU3PDl7PD;hQi=>
TT	M4TPUGZ2dmO2aX;uJGF{e2G7	NUfRe2JwOSEEtV2=	MoWwO\|IhcA>?	MoXFSG1UVw>?	MorabY5lfWOnczDHNUBjdG:la3Hn[S=>	NYPNSIRPRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOwOVY1QTlpPkKzNFU3PDl7PD;hQi=>
MZ-CRC1	NVG3fnNMSXCxcITvd4l{KEG\|c3H5	NIOy[GIyKML3TR?=	NV[xSXlVPDhiaB?=	NXXvNFl7TE2VTx?=	M1\zcIlv\HWlZYOgZZBweHSxc3nz	M4SxVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|MEW2OFk6Lz5{M{C1OlQ6QTxxYU6=
TT	NVnYcZRDSXCxcITvd4l{KEG\|c3H5	NGrsenMyKML3TR?=	M1[1[VQ5KGh?	NXq1d4NxTE2VTx?=	NWKzcmFpcW6mdXPld{BieG:ydH;zbZM>	MYO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzB3NkS5PUc,OjNyNU[0PVk9N2F-
HD-LM2	MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		MVq3NwKBkWh?	NI\USZdFVVOR	M2TsN2lEPTB;Nz64OFQh\|ryP	MVO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjh{OUC5OEc,OjJ6MkmwPVQ9N2F-
L-428	MlnjS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?		MlX3O\|LjiImq	NVviWYc1TE2VTx?=	NHHwe\|BKSzVyPUeuPVQ4KM7:TR?=	M4XoVVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OEK5NFk1Lz5{MkiyPVA6PDxxYU6=
KM-H2	NG\RepVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=		MmXGO\|LjiImq	MnzSSG1UVw>?	MYLJR\|UxRTFwM{C4JO69VQ>?	NWPVUGdkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK4NlkxQTRpPkKyPFI6ODl2PD;hQi=>
L-540	MYHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		NEH3TmI4OuLCiXi=	MmSxSG1UVw>?	NV\EUpI5UUN3ME24MlIyPiEQvF2=	NUjlUW5nRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK4NlkxQTRpPkKyPFI6ODl2PD;hQi=>
HD-LM2	MUHGeY5kfGmxbjDBd5NigQ>?	MWSwMlEwOC53L{GvOUDPxE1?	NHK1NZc4OuLCiXi=	NGe4WnlFVVOR	MVTpcohq[mm2czDTWGFVOyxiU2TBWFUh[W6mIGPURXQ3KHCqb4PwbI9zgWyjdHnvci=>	M1LnZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OEK5NFk1Lz5{MkiyPVA6PDxxYU6=
L-428	Mn:3SpVv[3Srb36gRZN{[Xl?	MoDrNE4yNzBwNT:xM\|Uh\|ryP	NV[zXZZiPzMkgJno	MljsSG1UVw>?	MVzpcohq[mm2czDTWGFVOyxiU2TBWFUh[W6mIGPURXQ3KHCqb4PwbI9zgWyjdHnvci=>	Moi2QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ6MkmwPVQoRjJ{OEK5NFk1RC:jPh?=
KM-H2	NHPIN5ZHfW6ldHnvckBCe3OjeR?=	NHr4NXkxNjFxMD61M\|EwPSEQvF2=	MorWO\|LjiImq	MXHEUXNQ	MYXpcohq[mm2czDTWGFVOyxiU2TBWFUh[W6mIGPURXQ3KHCqb4PwbI9zgWyjdHnvci=>	NIn5UWk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkiyPVA6PCd-MkK4NlkxQTR:L3G+
L-540	MWXGeY5kfGmxbjDBd5NigQ>?	MUKwMlEwOC53L{GvOUDPxE1?	NIPjWXM4OuLCiXi=	MXvEUXNQ	NFrhenpqdmirYnn0d{BUXEGWMzygV3RCXDViYX7kJHNVSVR4IIDoc5NxcG:{eXzheIlwdg>?	NUHjeWMyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK4NlkxQTRpPkKyPFI6ODl2PD;hQi=>
HD-LM2	M33nO2Fxd3C2b4Ppd{BCe3OjeR?=	NYWzW29nOS93IN88US=>	NFi1bHI4OuLCiXi=	MlLySG1UVw>?	MkTvbY5lfWOnczDhdI9xfG:\|aYO=	NE\DNWs9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkiyPVA6PCd-MkK4NlkxQTR:L3G+
L-428	NF\kfndCeG:ydH;zbZMhSXO\|YYm=	NX;ifIJOOS93IN88US=>	MYO3NwKBkWh?	MkPqSG1UVw>?	NVe0eWtScW6mdXPld{BieG:ydH;zbZM>	NE\XNno9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkiyPVA6PCd-MkK4NlkxQTR:L3G+
KM-H2	MVXBdI9xfG:\|aYOgRZN{[Xl?	NHfQ[\|YyNzVizszN	M4TrUVcz6oDLaB?=	NITaNGRFVVOR	NUHUNmJvcW6mdXPld{BieG:ydH;zbZM>	M2D3flxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OEK5NFk1Lz5{MkiyPVA6PDxxYU6=
L-540	NFXGNGVCeG:ydH;zbZMhSXO\|YYm=	NUjTVph4OS93IN88US=>	M4DFflcz6oDLaB?=	MWjEUXNQ	Mn;2bY5lfWOnczDhdI9xfG:\|aYO=	NWG3No5URGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK4NlkxQTRpPkKyPFI6ODl2PD;hQi=>
U251-MG	MnvJSpVv[3Srb36gRZN{[Xl?	MnfDNUDDvU1?	NWj4[4J7OC1zNjDo		NYjtbJFlcW6qaXLpeJMh[2:wc4TpeJV1cX[nIGPURXQuOyCjbnSgTmFMOiCjY4TpeoF1cW:w	M4XiRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MEK3OlkyLz5{MkCyO\|Y6OTxxYU6=
U87-MG	MnPESpVv[3Srb36gRZN{[Xl?	M2q5dFEhyrWP	MV6wMVE3KGh?		M1jQNIlvcGmkaYTzJINwdnO2aYT1eIl3\SCVVFHUMVMh[W6mIFrBT\|Ih[WO2aY\heIlwdg>?	NEX6SmM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkCyO\|Y6OSd-MkKwNlc3QTF:L3G+
4C8	MULGeY5kfGmxbjDBd5NigQ>?	MlTVNUDDvU1?	NG[3VYgxNTF4IHi=		MmTEbY5pcWKrdIOgZ49ve3SrdIX0bZZmKFOWQWStN{BidmRiSlHLNkBi[3SrdnH0bY9v	MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjB{N{[5NUc,OjJyMke2PVE9N2F-
U251-MG	NYrPdYN4T3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=	MW[xM\|ExKML3TR?=	MnfyNlQwPDhxN{KgbC=>		MkTvbY5pcWKrdIOgZ4VtdCCycn;sbYZmemG2aX;uJIF1KGFiY3;uZ4VvfHKjdHnvckBw\iBzMDFCuW0>	M{O3OFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MEK3OlkyLz5{MkCyO\|Y6OTxxYU6=
U87-MG	M17FVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MXGxM\|ExKML3TR?=	MnexNlQwPDhxN{KgbC=>		MULpcohq[mm2czDj[YxtKHC{b3zp[oVz[XSrb36gZZQh[SClb37j[Y51emG2aX;uJI9nKDFyINM1US=>	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjB{N{[5NUc,OjJyMke2PVE9N2F-
4C8	M3LLVGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MnzPNU8yOCEEtV2=	Mly3NlQwPDhxN{KgbC=>		MX7pcohq[mm2czDj[YxtKHC{b3zp[oVz[XSrb36gZZQh[SClb37j[Y51emG2aX;uJI9nKDFyINM1US=>	MlLGQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJyMke2PVEoRjJ{MEK3OlkyRC:jPh?=
U266	MlnmRZBweHSxc3nzJGF{e2G7	NUjwdFlNOC53LUKg{txO	NImwZVc1QC95MjDo		MofnbY5lfWOnczDhdI9xfG:\|aYOg[I9{\SCmZYDlcoRmdnSueR?=	Moq0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzNkS1NVcoRjJzMU[0OVE4RC:jPh?=
Kms.11	NX\sZYdESXCxcITvd4l{KEG\|c3H5	Mlm4NE42NTJizszN	NHHhfJQ1QC95MjDo		M{n6RYlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm=	NH;iXWU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUG2OFUyPyd-MkGxOlQ2OTd:L3G+
8226	MYfBdI9xfG:\|aYOgRZN{[Xl?	Mk\FNE42NTJizszN	NUGxR3l{PDhxN{KgbC=>		MXzpcoR2[2W\|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7	NWPQbZpZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxOlQ2OTdpPkKxNVY1PTF5PD;hQi=>
SET2	M3O1TGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7		Mlm5OFghcHK\|		NGLyfmxIem:5dHigbY5pcWKrdHnvckBw\iCqdX3hckBUTVR{IHPlcIx{KGW6cILld5NqdmdiSnHrNkBXPjF5RjDteZRidnRiYX\0[ZIhPDhiaILzJIJ6KE2WUzDhd5NigSxiR1m1NEA:KDBwMEG2JO69VS5?	MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF\|OEK0Okc,OjFzM{iyOFY9N2F-
SET2	MVPGeY5kfGmxbjDhd5NigQ>?		NIHzSZEyKGi{		M17zT2lvcGmkaYTpc44hd2ZiU4TheFMheGixc4Doc5J6dGG2aX;uJIlvKGi3bXHuJHNGXDJiY3XscJMh[W[2ZYKgNUBpeiCkeTDX[ZN1\XKwIHLsc5R1cW6pLDDJR\|UxKD1iMD6wNlMh\|ryPLh?=	NELTVHk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUGzPFI1Pid-MkGxN\|gzPDZ:L3G+
SET2	NVu1bXpWTnWwY4Tpc44h[XO\|YYm=		M16yXVEhcHJ?		M1nZO2lvcGmkaYTpc44hd2ZiU4TheFUheGixc4Doc5J6dGG2aX;uJIlvKGi3bXHuJHNGXDJiY3XscJMh[W[2ZYKgNUBpeiCkeTDX[ZN1\XKwIHLsc5R1cW6pLDDJR\|UxKD1iMD6wNlUh\|ryPLh?=	NGfZbog9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUGzPFI1Pid-MkGxN\|gzPDZ:L3G+
HEL	MUTGeY5kfGmxbjDhd5NigQ>?		M{HiV\|EhcHJ?		NH61eXdKdmirYnn0bY9vKG:oIGP0ZZQ2KHCqb4PwbI9zgWyjdHnvckBqdiCqdX3hckBJTUxiY3XscJMh[W[2ZYKgNUBpeiCkeTDX[ZN1\XKwIHLsc5R1cW6pLDDJR\|UxKD1iMD6wOFEh\|ryPLh?=	MVK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF\|OEK0Okc,OjFzM{iyOFY9N2F-
Ba/F3	NFX2d2VHfW6ldHnvckBie3OjeR?=				NWTYS3VEUW6qaXLpeIlwdiCxZjDTeIF1PSCyaH;zdIhwenmuYYTpc44hcW5ibX;1d4UhSmFxRkOgZ4VtdHNiZYjwdoV{e2mwZzDUSWwuUmGtMjygTWM2OCB;IECuNFQ3KM7:TT6=	NWTPXVZNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxN\|gzPDZpPkKxNVM5OjR4PD;hQi=>
UKE1	MVLHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?		NXzlOHhPPDhiaILz		NYXzVGVVT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hXUuHMTDj[YxteyCneIDy[ZN{cW6pIFrhb\|IhXjZzN1[gcZV1[W62IHHmeIVzKDR6IHjyd{BjgSCPVGOgZZN{[XluIFfJOVAhRSByLkC1OEDPxE1w	M1fXclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
BA/F3	MmXMS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		MlLsOFghcHK\|		NInuVotIem:5dHigbY5pcWKrdHnvckBw\iCvb4Xz[UBDSS:IMzDj[YxteyCneIDy[ZN{cW6pIGTlcE1LSUt{IHvpcoF{\SCjZoTldkA1QCCqcoOgZpkhVVSVIHHzd4F6NCCJSUWwJF0hOC5yNjFOwG0v	NHu4OFA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUGzPFI1Pid-MkGxN\|gzPDZ:L3G+
HEL	M2radGZ2dmO2aX;uJIF{e2G7		MWGxJIhz		MX\Jcohq[mm2aX;uJI9nKFO2YYSzJJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDISWwh[2WubIOgZYZ1\XJiMTDodkBjgSCZZYP0[ZJvKGKub4T0bY5oNCCLQ{WwJF0hOC5yODFOwG0v	NVzBW\|ZFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxN\|gzPDZpPkKxNVM5OjR4PD;hQi=>
HEL	NGm1OIJIem:5dHigbY5pcWKrdHnvckBie3OjeR?=		MYO0PEBpenN?		NVnzPYE5T3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hUEWOIHPlcIx{KGW6cILld5NqdmdiSnHrNkBXPjF5RjDteZRidnRiYX\0[ZIhPDhiaILzJIJ6KE2WUzDhd5NigSxiR1m1NEA:KDBwM{mg{txONg>?	MWi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF\|OEK0Okc,OjFzM{iyOFY9N2F-
BA/F3	NX\XdVR3T3Kxd4ToJIlvcGmkaYTpc44h[XO\|YYm=		MYS0PEBpenN?		MlXBS5Jwf3SqIHnubIljcXSrb36gc4YhdW:3c3WgRmEwTjNiY3XscJMh\XiycnXzd4lv\yCWZXytTmFMOSCtaX7hd4Uh[W[2ZYKgOFghcHK\|IHL5JG1VWyCjc4PhfUwhT0l3MDC9JFAvPyEQvF2u	M3y5[\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
BA/F3	MnrnS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl?		Mn;ROFghcHK\|		MWPHdo94fGhiaX7obYJqfGmxbjDv[kBud3W\|ZTDCRU9HOyClZXzsd{BmgHC{ZYPzbY5oKFSnbD3UfYszKGurbnHz[UBi\nSncjC0PEBpenNiYomgUXRUKGG\|c3H5MEBIUTVyIE2gNkDPxE1w	NG\2fnQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUGzPFI1Pid-MkGxN\|gzPDZ:L3G+
BA/F3	MVvHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>?		NEfk[Hc1QCCqcoO=		Mn6xS5Jwf3SqIHnubIljcXSrb36gc4YhdW:3c3WgRmEwTjNiY3XscJMh\XiycnXzd4lv\yCWZXytTmFMOyCtaX7hd4Uh[W[2ZYKgOFghcHK\|IHL5JG1VWyCjc4PhfUwhT0l3MDC9JFIvOSEQvF2u	NIrVRY09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUGzPFI1Pid-MkGxN\|gzPDZ:L3G+
UKE1	NIX3e\|ZHfW6ldHnvckBie3OjeR?=		M1XmflEhcHJ?		MXPJcohq[mm2aX;uJI9nKFO2YYS1JJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDVT2UyKGOnbHzzJIFnfGW{IEGgbJIh[nliV3XzeIVzdiCkbH;0eIlv\w>?	NVnzXGl6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxN\|gzPDZpPkKxNVM5OjR4PD;hQi=>
SW620	NHTifINE\WyuIHP5Z4xmKGG\|c3H5	MkjYN{4{KHWP	MUOyOEBpenN?		MlnZR4VtdCCleXPs[UBienKnc4SgbY4hcHWvYX6gV3c3OjBiY3XscJMh[XO\|ZYPz[YQh[XNiYXPjeY12dGG2aX;uJIF1KEd{L12gdIhie2ViYYSgN{4{KHWPIHHmeIVzKDJ2IHjyd{BjgSCobH;3JIN6fG:vZYTyfS=>	NFrLdHE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUGzPFI1Pid-MkGxN\|gzPDZ:L3G+
HEL	NHXKcnZHfW6ldHnvckBie3OjeR?=	MXewMlMhfU1?	MnHiOUBucW6\|		MlToTY5pcWKrdHnvckBw\iCVdHH0OUBxcG:\|cHjvdplt[XSrb36gbY4hcHWvYX6gTGVNKGOnbHzzJIF1KDBwMzD1UUBi\nSncjC1JI1qdnNiYomgW4V{fGW{bjDicI91fGmwZx?=	NWXK[XhFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxN\|gzPDZpPkKxNVM5OjR4PD;hQi=>
HEL	NEHEZ5VHfW6ldHnvckBie3OjeR?=	MofPNE4{KHWP	MnjPN\|AhfG9iNkCgcYlvew>?		NWXJZ25LUW6qaXLpeIlwdiCxZjDTeIF1PSCyaH;zdIhwenmuYYTpc44hcW5iaIXtZY4hUEWOIHPlcIx{KGG2IECuN{B2VSCjZoTldkA{OCC2bzC2NEBucW6\|IHL5JHdme3Sncn6gZoxwfHSrbne=	MmDqQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzM{iyOFYoRjJzMUO4NlQ3RC:jPh?=
BA/F3	MUDBcpRqfHWvb4KgZZN{[Xl?	M1X6SVMxKG2pL3vn	M4PibFEzKGi{cx?=		MVPBcpRqfHWvb4KgZYN1cX[rdImgZYdicW6\|dDDtc5V{\SCEQT;GN{Bk\WyuczDlfJBz\XO\|aX7nJHRmdC2MQVuyJJhmdm:pcnHmeIVlKGmwIF7DdkBud3W\|ZTDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hd2ZicHjvd5Bpd3K7bHH0[YQhW3SjdEWgcIV3\WxiaX6gd5Bt\WWwIHH0JFMxKG2pL3vnMEBxdyCjZoTldkAyOiCqcoOgZpkhX2W\|dHXyckBjdG:2dHnu[y=>	M3q2e\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
HEL	NGXLTpNHfW6ldHnvckBie3OjeR?=	NVXEWYw2OC5\|IIXN	NGX4TJU2KG2rboO=		MV3Jcohq[mm2aX;uJI9nKFO2YYSzJJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDISWwh[2WubIOgZZQhOC5\|IIXNJIFnfGW{IEWgcYlveyCkeTDX[ZN1\XKwIHLsc5R1cW6p	MoKyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzM{iyOFYoRjJzMUO4NlQ3RC:jPh?=
HEL	MkXOSpVv[3Srb36gZZN{[Xl?	NFH1Zm0xNjNidV2=	NFzzVnI{OCC2bzC2NEBucW6\|		MXjJcohq[mm2aX;uJI9nKFO2YYSzJJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDISWwh[2WubIOgZZQhOC5\|IIXNJIFnfGW{IEOwJJRwKDZyIH3pcpMh[nliV3XzeIVzdiCkbH;0eIlv\w>?	M{\Yd\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
Hs578T	Ml3hSpVv[3Srb36gZZN{[Xl?	NXPn[IVEOSC3TR?=	NVTwSWpiOjRiaILz		NILSVVFKdmirYnn0bY9vKG:oIGPURXQ{Sy2vZXTpZZRm\CC2cnHud4NzcXC2aX;uJIlvKGi3bXHuJGh{PTd6VDDj[YxteyCjdDCxJJVOKGGodHXyJFI1KGi{czDifUBtfWOrZnXyZZNmKHKncH;yeIVzKGenbnWgZZN{[Xl?	NYPnW\|NuRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5O\|gyOTJpPkK0PVc5OTF{PD;hQi=>
NCI-H1975	M2q3cGZ2dmO2aX;uJIF{e2G7	NXTHfGh1OC5yMEOgeI8hOyC3TR?=	MnPDNkBpenN?		NVKySnNbUW6qaXLpeIlwdiCxZjDKRWsyKGmwIHj1cYFvKE6FST3INVk4PSClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25iaX6gV3RCXDNicHjvd5Bpd3K7bHH0bY9vKGG2IECuNFA{KHSxIEOgeW0h[W[2ZYKgNkBpenNiYomgW4V{fGW{bjDicI91KGGwYXz5d4l{	M2TpUVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NkG0OFA5Lz5{Nk[xOFQxQDxxYU6=
HEL 92.1.7	M3HmbWZ2dmO2aX;uJIF{e2G7		NFXLdIQzKGi{cx?=		NIDhcnZKdmirYnn0bY9vKG:oIFrBT\|IhcW5iaIXtZY4hUEWOIEmyMlEvPyClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25iaX6gV3RCXDVicHjvd5Bpd3K7bHH0bY9vKGGodHXyJFIhcHK\|IHL5JHdme3Sncn6gZoxwfCCjbnHsfZNqew>?	MkXjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ4MUS0NFgoRjJ4NkG0OFA5RC:jPh?=
DAOY	MoDTdWhVWyCjc4PhfS=>				NUDtdohieUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFTBU3kh[2WubIO=	MmLzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
SJ-GBM2	NV7hfHQxeUiWUzDhd5NigQ>?				M4C3XZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVSj3HRm0zKGOnbHzz	M2rVe\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
A673	NYfWWWJ[eUiWUzDhd5NigQ>?				M1z1RpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCDNkezJINmdGy\|	MYe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-MC	NF3FeJZyUFSVIHHzd4F6				MVfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0tvTj3NR{Bk\Wyucx?=	M1u0dFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
BT-37	NIDlZnNyUFSVIHHzd4F6				NUHPSZQ5eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFLUMVM4KGOnbHzz	NWDUcHdDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
NB-EBc1	NVLwfHo1eUiWUzDhd5NigQ>?				NY\nSZNqeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF7CMWVD[zFiY3XscJM>	M4PZUlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
Saos-2	MofGdWhVWyCjc4PhfS=>				M1rJS5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVYX;zMVIh[2WubIO=	NHfJb5g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SK-N-SH	MnT2dWhVWyCjc4PhfS=>				MlyzdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFONLV6tV2gh[2WubIO=	MkflQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
NB1643	MWfxTHRUKGG\|c3H5				Mn;1dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6EMU[0N{Bk\Wyucx?=	MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
BT-12	NV;QXFg{eUiWUzDhd5NigQ>?				MlHEdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUGyJINmdGy\|	MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
OHS-50	NY[wRVROeUiWUzDhd5NigQ>?				MV3xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhV0iVLUWwJINmdGy\|	M1nxfVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
RD	Mke0dWhVWyCjc4PhfS=>				NELubpVyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUlSgZ4VtdHN?	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
MG 63 (6-TG R)	NFP4NXRyUFSVIHHzd4F6				MoPqdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE2JIE[zJEg3NVSJIGKpJINmdGy\|	NYHP[VVNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh41	MV7xTHRUKGG\|c3H5				M2jMTpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaESxJINmdGy\|	NHG4RXo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+

... 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 2022-01-17)

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98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 2022-01-17)

技术支持

JAK Signaling Pathway Map

JAK Inhibitors with Unique Features

相关JAK产品