AZD1480

For research use only. Not for use in humans.

目录号:S2162

AZD1480 Chemical Structure

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
RMB 819.48 现货
RMB 4671.71 现货
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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

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-
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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=>
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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=
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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=>
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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?=
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GLC4 M1S0O2Z2dmO2aX;uJGF{e2G7 M2DiXVAvOy9zL{Og{txO MXOyOEBp NHrMR3NqdmS3Y3XzJGczN01iY3XscEBkgWOuZTDhdpJme3R? NFr6O|Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEG1PFcxOSd-MkSxOVg4ODF:L3G+
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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=
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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=>
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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     


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     


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     


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     


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     


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     


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]

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)

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 Km (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)

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

分子量 348.77
化学式

C14H14ClFN8

CAS号 935666-88-9
储存条件 粉状
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 g 每只动物给药体积 ul 动物数量
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

计算器

摩尔浓度计算器

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

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

  • 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

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

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

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

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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。

  • * 必填项

JAK Signaling Pathway Map

JAK Inhibitors with Unique Features

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID