AZD1480

Catalog No.S2162

For research use only.

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

AZD1480 Chemical Structure

CAS No. 935666-88-9

Selleck's AZD1480 has been cited by 95 publications

Purity & Quality Control

Choose Selective JAK Inhibitors

Other JAK Products

Biological Activity

Description AZD1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of 0.26 nM in a cell-free assay, selectivity against JAK3 and Tyk2, and to a smaller extent against JAK1. Phase 1.
Targets
JAK2 [1]
(Cell-free assay)
0.26 nM
In vitro

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

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
SW620 NVi2UYxpTnWwY4Tpc44hSXO|YYm= NIe2Vno2KM7:TR?= M1;5dFQ5KGh? MYXEUXNQ MoXJZoxw[2u|IFrBT|IwW1SDVEOgd4lodmGuaX7n MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTl3NEm3OEc,OjV7NUS5O|Q9N2F-
LoVo  M3nXcmZ2dmO2aX;uJGF{e2G7 NVe2V5AzPSEQvF2= M3HxWVQ5KGh? MnXMSG1UVw>? Mn6zZoxw[2u|IFrBT|IwW1SDVEOgd4lodmGuaX7n M{jmclxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OUW0PVc1Lz5{NUm1OFk4PDxxYU6=
HN5 NYfyfllkT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX;We5FxPzJiaB?= M{TiOGVEPTB;Mz64NUDDuSBzLkm5JO69VQ>? MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPThzMECxNEc,OjV6MUCwNVA9N2F-
Cal33 MX\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NY[2XZJjPzJiaB?= NHO3e49GSzVyPUOuN|chyrFiMD63OUDPxE1? NFrFToU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUixNFAyOCd-MkW4NVAxOTB:L3G+
UM-22B MY\Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NI\aW3E4OiCq MkDjSWM2OD1{Lk[2JOKyKDBwMkSg{txO MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPThzMECxNEc,OjV6MUCwNVA9N2F-
686LN MWPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWK3NkBp M3nJXGVEPTB;Mj6wOUDDuSBzLkOzJO69VQ>? M4PRTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEGwNFExLz5{NUixNFAyODxxYU6=
UM SCC-1 NWHyfWlCT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MnSyO|IhcA>? M3TmfmVEPTB;MT62O{DDuSByLkSyJO69VQ>? M1TNU|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEGwNFExLz5{NUixNFAyODxxYU6=
UM-22A NYnY[odLT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYG3NkBp MXLFR|UxRTFwM{KgxtEhOC5|OTFOwG0> NGLmZVM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUixNFAyOCd-MkW4NVAxOTB:L3G+
OSC19 NFj5ZnZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NUnYNIl[PzJiaB?= MYPFR|UxRTFwMk[gxtEhOC5{MDFOwG0> M{C3U|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEGwNFExLz5{NUixNFAyODxxYU6=
PCI-52 NX;xSJlGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4jsO|czKGh? Ml7DSWM2OD1zLkCwJOKyKDBwMEmg{txO Ml3aQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6MUCwNVAoRjJ3OEGwNFExRC:jPh?=
PCI-15B NXT6cXptT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUK3NkBp Mon0SWM2OD1yLkm5JOKyKDFwN{Sg{txO NV7XVmdvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4NVAxOTBpPkK1PFExODFyPD;hQi=>
UMSCC-1 M1;PSmZ2dmO2aX;uJGF{e2G7 NGnwNFUxNjByMEWtNU43KM7:TR?= NVzNTlh7OjRiaB?= MoDlZYJzd2ejdHXzJGlNNTckgKPpcoR2[2WmIIXwMZJm\3WuYYTpc44hd2ZicGPURXQ{XHm{N{C1xsBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> NEn2NnA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUixNFAyOCd-MkW4NVAxOTB:L3G+
Cal33 M4rucGZ2dmO2aX;uJGF{e2G7 MWKwMlAxODVvMz64JO69VQ>? M2[3OVI1KGh? NGC0XY5i[nKxZ3H0[ZMhUUxvNvMAl4lv\HWlZXSgeZAuemWpdXzheIlwdiCxZjDwV3RCXDOWeYK3NFXDqGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz M37qV|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3OEGwNFExLz5{NUixNFAyODxxYU6=
HH5 MV;GeY5kfGmxbjDBd5NigQ>? Mn\lNE4xODB3LUOuPEDPxE1? M2\aOlI1KGh? MYrhZpJw\2G2ZYOgTWwuPuLCk3nu[JVk\WRidYCtdoVofWyjdHnvckBw\iCyU2TBWFNVgXJ5MEZCpIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy NH;jfmM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUixNFAyOCd-MkW4NVAxOTB:L3G+
UM-22A NELKVVNHfW6ldHnvckBCe3OjeR?= NU[wblEyOC5yMEC1MVEvPiEQvF2= NGXa[mwzPCCq MkW3ZYJzd2ejdHXzJGlNNTckgKPpcoR2[2WmIIXwMZJm\3WuYYTpc44hd2ZicGPURXQ{XHm{N{C1xsBqdiCjIHTvd4Uu\GWyZX7k[Y51KG2jbn7ldi=> MnSyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6MUCwNVAoRjJ3OEGwNFExRC:jPh?=
A1847 M4OyT2Z2dmO2aX;uJGF{e2G7 M4Xx[FAvODVvMUCg{txO MYSyOEBp NEDxfXdFVVORwrC= MWLy[YR2[2W|IIDoc5NxcG:{eXzheIVlKFOWQWSzJIxmfmWucx?= M4nZV|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkS2NFE2Lz5{NU[0OlAyPTxxYU6=
OVCAR-5 MVTGeY5kfGmxbjDBd5NigQ>? NWXiWnZjOC5yNT2xNEDPxE1? MUeyOEBp NEe2Z3FFVVORwrC= MlHJdoVlfWOnczDwbI9{eGixconsZZRm\CCVVFHUN{Bt\X[nbIO= M{DlNVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkS2NFE2Lz5{NU[0OlAyPTxxYU6=
OVCAR-8 MlznSpVv[3Srb36gRZN{[Xl? NFfofosxNjB3LUGwJO69VQ>? NVvJRoFvOjRiaB?= MV;EUXNQyqB? M4DvbpJm\HWlZYOgdIhwe3Cqb4L5cIF1\WRiU2TBWFMhdGW4ZXzz MlnJQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV4NE[wNVUoRjJ3NkS2NFE2RC:jPh?=
MOVCAR-5447 MlKxSpVv[3Srb36gRZN{[Xl? MmHuNE4xPS1zMDFOwG0> NGnOXFIzPCCq NWnQSJpOTE2VT9Mg NHfiUWtz\WS3Y3XzJJBpd3OyaH;yfYxifGWmIGPURXQ{KGyndnXsdy=> MnTpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV4NE[wNVUoRjJ3NkS2NFE2RC:jPh?=
MOVCAR-5009 MWfGeY5kfGmxbjDBd5NigQ>? MXqwMlA2NTFyIN88US=> MUOyOEBp MWLEUXNQyqB? NWS3OnFjemWmdXPld{BxcG:|cHjvdplt[XSnZDDTWGFVOyCuZY\lcJM> M4TDdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkS2NFE2Lz5{NU[0OlAyPTxxYU6=
A1847 MoriR4VtdCCYaXHibYxqfHliQYPzZZk> MorWNE4xPS1zMDFOwG0> MmnIO|IhcA>? NGHCZ5NFVVOR MYHy[YR2[2W|IHPlcIwhfmmjYnnsbZR6KGG2IITo[UBkd26lZYLueJJifGmxbjDv[kA2KM7:TR?= MUW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ2NkCxOUc,OjV4NE[wNVU9N2F-
OVCAR-5 MVzD[YxtKF[rYXLpcIl1gSCDc4PhfS=> NULWfZM5OC5yNT2xNEDPxE1? MmXvO|IhcA>? M{LvTWROW09? MmTndoVlfWOnczDj[YxtKH[rYXLpcIl1gSCjdDD0bIUh[2:wY3XycpRz[XSrb36gc4YhPSEQvF2= MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTZ2NkCxOUc,OjV4NE[wNVU9N2F-
OVCAR-8  MkHBR4VtdCCYaXHibYxqfHliQYPzZZk> NEPmR5QxNjB3LUGwJO69VQ>? MUK3NkBp NYX5[ZhzTE2VTx?= MoLVdoVlfWOnczDj[YxtKH[rYXLpcIl1gSCjdDD0bIUh[2:wY3XycpRz[XSrb36gc4YhPSEQvF2= NEG3dXE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NU[0OlAyPSd-MkW2OFYxOTV:L3G+
OVCAR-5  NH;DcZpCeG:ydH;zbZMhSXO|YYm= M2LFSVAvPS9zL{Wg{txO MX[0PEBp MVHEUXNQ MWPpcoR2[2W|IIPp[45q\mmlYX70JIFxd3C2b4Ppd{BifCCqaXfoJINwdmOncn70doF1cW:w M{jhflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3NkS2NFE2Lz5{NU[0OlAyPTxxYU6=
OVCAR-8  NFvrSlBCeG:ydH;zbZMhSXO|YYm= NVLWT4VPOC53L{GvOUDPxE1? NXPaPIhEPDhiaB?= NF;y[XNFVVOR MX;pcoR2[2W|IIPp[45q\mmlYX70JIFxd3C2b4Ppd{BifCCqaXfoJINwdmOncn70doF1cW:w NYrmRWVqRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW2OFYxOTVpPkK1OlQ3ODF3PD;hQi=>
AKRSL MXvD[YxtKF[rYXLpcIl1gSCDc4PhfS=> MXS3NkBp MkTUTWM2OO,:nkGwJO69VQ>? MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTVyNE[zOUc,OjV3MES2N|U9N2F-
PALJDL MnLrR4VtdCCYaXHibYxqfHliQYPzZZk> Mlv3O|IhcA>? NFTsSodKSzVyPUKuOEDPxE1? NFz1ZVE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUWwOFY{PSd-MkW1NFQ3OzV:L3G+
MO4 NFTyfI5HfW6ldHnvckBCe3OjeR?= MXGwMlUwOS93IN88US=> MWm2JIg> M371TYlvcGmkaYTzJHAuW1SDVEOg[ZhxemW|c3nvcuKh MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTF2OUWzOUc,OjVzNEm1N|U9N2F-
DU145  NFzBZ3NHfW6ldHnvckBCe3OjeR?= Mki0NE0zODBibl2= MnzRNUBpyqB? NFP4WFB{fXCycnXzd4V{KEmOLU[tZYN1cX[jdHXkJHN1[XR|IHHu[EBGWktzL{Kgd4lodmGuaX7n MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDV5N{m0Nkc,OjR3N{e5OFI9N2F-
DU145  MlXHSpVv[3Srb36gRZN{[Xl? MoqyPFAxKG6P NXfvO5dkPzJiaB?= MVnzeZBxemW|c3XzJGlNNTZvaX7keYNm\CCvaXfyZZRwenl? MorHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR3N{e5OFIoRjJ2NUe3PVQzRC:jPh?=
CWR22Rv1 Mmf5SpVv[3Srb36gRZN{[Xl? MkDHPFAxKG6P NWj5RnBmPzJiaB?= MUXzeZBxemW|c3XzJGlNNTZvaX7keYNm\CCvaXfyZZRwenl? NXPaPWJVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS1O|c6PDJpPkK0OVc4QTR{PD;hQi=>
N592 MUfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYrJR|UxRTBwOESg{txO M3W3Z|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2MUW4O|AyLz5{NEG1PFcxOTxxYU6=
H82 MnLFS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVP3SnBwUUN3ME2xMlM4KM7:TR?= MlrrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzNUi3NFEoRjJ2MUW4O|AyRC:jPh?=
GLC4 NIXofYJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWnJR|UxRTFwN{mg{txO NXTpZnFTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSxOVg4ODFpPkK0NVU5PzBzPD;hQi=>
H526 NITIVpFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYHJR|UxRTNwMEig{txO NXPwWVhVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSxOVg4ODFpPkK0NVU5PzBzPD;hQi=>
H1173 M2nRRWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmPoTWM2OD1{LkO5JO69VQ>? MkP6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzNUi3NFEoRjJ2MUW4O|AyRC:jPh?=
DMS114 NVG2WnN3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NF6yXJlKSzVyPUCuO|Mh|ryP NELLS2k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEG1PFcxOSd-MkSxOVg4ODF:L3G+
NCI-N592 MoXBSpVv[3Srb36gRZN{[Xl? MV:wMlMwOS9|IN88US=> MYqyOEBp MV3pcoR2[2W|IFeyM20h[2WubDDjfYNt\SCjcoLld5Q> NWf0cJhQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkSxOVg4ODFpPkK0NVU5PzBzPD;hQi=>
GLC4 MlT5SpVv[3Srb36gRZN{[Xl? MoDjNE4{NzFxMzFOwG0> MVGyOEBp M{PhRolv\HWlZYOgS|IwVSClZXzsJIN6[2ynIHHydoV{fA>? MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF3OEewNUc,OjRzNUi3NFE9N2F-
NCI-H82 NGO4Z|hHfW6ldHnvckBCe3OjeR?= NFi4V3cxNjNxMT:zJO69VQ>? MWSyOEBp MXPpcoR2[2W|IFeyM20h[2WubDDjfYNt\SCjcoLld5Q> NFrx[2g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEG1PFcxOSd-MkSxOVg4ODF:L3G+
NCI-N592 MlHnRZBweHSxc3nzJGF{e2G7 M1S5VFAvOy9zL{Og{txO MkL2OFghcA>? MnXUbY5kemWjc3XzJJRp\SCuZY\lcEBw\iClbHXheoVlNUOjc4Dhd4UhOw>? MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF3OEewNUc,OjRzNUi3NFE9N2F-
GLC4 NIPVcJZCeG:ydH;zbZMhSXO|YYm= NGXXfI8xNjNxMT:zJO69VQ>? M3fjbFQ5KGh? M2PZXolv[3KnYYPld{B1cGVibHX2[Ywhd2ZiY3zlZZZm\C2FYYPwZZNmKDN? MX68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDF3OEewNUc,OjRzNUi3NFE9N2F-
NCI-H82 NWLFSmx{SXCxcITvd4l{KEG|c3H5 NEDjT|MxNjNxMT:zJO69VQ>? NIDoNIw1QCCq M1i1SIlv[3KnYYPld{B1cGVibHX2[Ywhd2ZiY3zlZZZm\C2FYYPwZZNmKDN? Mo\BQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRzNUi3NFEoRjJ2MUW4O|AyRC:jPh?=
CWR22Rv1  M1r4NmFxd3C2b4Ppd{BCe3OjeR?= MkPoTWM2OD1yLkS4NkDPxE1? NFu5S2E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{m0NlA6PSd-MkO5OFIxQTV:L3G+
CWR22Pc MVLBdI9xfG:|aYOgRZN{[Xl? M{LifmlEPTB;MD60N|gh|ryP MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzl2MkC5OUc,OjN7NEKwPVU9N2F-
PC-3 NFrkVHdCeG:ydH;zbZMhSXO|YYm= MlP6TWM2OD1zLke1OUDPxE1? NFrGdGM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{m0NlA6PSd-MkO5OFIxQTV:L3G+
DU145 NWHtSFhCSXCxcITvd4l{KEG|c3H5 MkD5TWM2OD1|LkWxO{DPxE1? MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzl2MkC5OUc,OjN7NEKwPVU9N2F-
RC165N M2DBVGFxd3C2b4Ppd{BCe3OjeR?= M4PqUWlEPTB;Mj6wPFMh|ryP MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzl2MkC5OUc,OjN7NEKwPVU9N2F-
ARPE19 M3Xsc2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NH\K[IdFVVOR M4rrTGlEPTB;MkSuN|gh|ryP MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV|MUmyNUc,OjN3M{G5NlE9N2F-
HEK293 Mmm1S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn7KSG1UVw>? M{HPcGlEPTB;OD62O{DPxE1? NHv4[pc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N|E6OjF:L3G+
KCNR Mn7IS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M1T5dWROW09? NH73d2xKSzVyPUCuOFYh|ryP NY\RVnBWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N|E6OjFpPkKzOVMyQTJzPD;hQi=>
SY5Y NHq1WXVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MmDBSG1UVw>? M2fCRWlEPTB;MD6zOkDPxE1? NWPIVnhrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N|E6OjFpPkKzOVMyQTJzPD;hQi=>
BE2 NHfIVVhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MoPjSG1UVw>? NG\yRlBKSzVyPUCuO|Eh|ryP MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV|MUmyNUc,OjN3M{G5NlE9N2F-
AS MXTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MVnEUXNQ MkftTWM2OD1zLkWzJO69VQ>? NYLlTGt7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N|E6OjFpPkKzOVMyQTJzPD;hQi=>
NGP MoHYS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MXrEUXNQ MWDJR|UxRTBwNU[g{txO NYDlcXZCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N|E6OjFpPkKzOVMyQTJzPD;hQi=>
IMR32 M17uTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MmHYSG1UVw>? M3fO[2lEPTB;MD62OkDPxE1? MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV|MUmyNUc,OjN3M{G5NlE9N2F-
LAN5 NVjae|hOT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGTsO2pFVVOR M1jrRWlEPTB;MT6wOEDPxE1? MlO0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ|NUOxPVIyRC:jPh?=
RH18 M3nFfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MYDEUXNQ M2fMbmlEPTB;MT60NkDPxE1? Mom4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ|NUOxPVIyRC:jPh?=
RH30 MUjHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYnEUXNQ MXHJR|UxRTFwMkWg{txO NY[0XnVXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N|E6OjFpPkKzOVMyQTJzPD;hQi=>
RH17 NW\MN3F{T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHfydoNFVVOR MXzJR|UxRTJwNUGg{txO MoLIQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ|NUOxPVIyRC:jPh?=
RH28 NX7rcnh6T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUPEUXNQ Mme3TWM2OD12LkK4JO69VQ>? M3rQdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NUOxPVIyLz5{M{WzNVkzOTxxYU6=
RH36 Mnz6S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mn3OSG1UVw>? MYPJR|UxRTVwM{eg{txO NWXqRlFMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N|E6OjFpPkKzOVMyQTJzPD;hQi=>
RH41 MUTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2D6SWROW09? MWjJR|UxRTBwNEig{txO NHO4XZQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N|E6OjF:L3G+
RD NY\1VFVtT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MYXEUXNQ MUHJR|UxRTRwM{Kg{txO MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV|MUmyNUc,OjN3M{G5NlE9N2F-
TC32 MUPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MUjEUXNQ NIT6O5dKSzVyPUOuPFUh|ryP Mn\QQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3M{G5NlEoRjJ|NUOxPVIyRC:jPh?=
TC71 NYPmOnNYT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWr5dYZGTE2VTx?= NWfySWpvUUN3ME20MlM{KM7:TR?= M3KzSlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NUOxPVIyLz5{M{WzNVkzOTxxYU6=
KCNR M2TjS2Fxd3C2b4Ppd{BCe3OjeR?= MWqwMlUwOS5yL{KuOUDPxE1? MnPDNlQhcA>? M4nwNmROW09? M1L6SIlv\HWlZYOgZY4hcW6lcnXhd4UhcW5iY3HzdIF{\SB|L{egZYN1cX[rdIm= M{LRT|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NUOxPVIyLz5{M{WzNVkzOTxxYU6=
SY5Y MnHQRZBweHSxc3nzJGF{e2G7 M1;rTFAvPS9zLkCvNk42KM7:TR?= NXfOeHViOjRiaB?= MmixSG1UVw>? NHLqSGNqdmS3Y3XzJIFvKGmwY4LlZZNmKGmwIHPhd5Bie2ViMz:3JIFkfGm4aYT5 M3O0XFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NUOxPVIyLz5{M{WzNVkzOTxxYU6=
Rh18 NHzCPYdCeG:ydH;zbZMhSXO|YYm= M4P2W|AvPS9zLkCvNk42KM7:TR?= M1Gy[lI1KGh? MkS1SG1UVw>? NUDJSVZwcW6mdXPld{BidiCrbnPy[YF{\SCrbjDjZZNx[XOnIEOvO{Bi[3Srdnn0fS=> NITZ[2I9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N|E6OjF:L3G+
TC32 MUXBdI9xfG:|aYOgRZN{[Xl? MlnINE42NzFwMD:yMlUh|ryP NYnNRo02OjRiaB?= MXXEUXNQ M2jrTYlv\HWlZYOgZY4hcW6lcnXhd4UhcW5iY3HzdIF{\SB|L{egZYN1cX[rdIm= M3TYUlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NUOxPVIyLz5{M{WzNVkzOTxxYU6=
KCNR NGfwc4VHfW6ldHnvckBCe3OjeR?= NV21WoFCOC53L{GuNE8zNjVxNTFOwG0> MlfoNlQhcA>? MWLEUXNQ NXuzPJlJcW6qaXLpeJMh[m:2aDDlcoRw\2Wwb4XzJINwdnO2aYT1eIl3\SCjbnSgTWwuPi2rbnT1Z4VlKFOWQWSzJIFkfGm4YYTpc44> MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV|MUmyNUc,OjN3M{G5NlE9N2F-
SY5Y MWDGeY5kfGmxbjDBd5NigQ>? M{XMOFAvPS9zLkCvNk42NzVizszN MXiyOEBp M2q0[GROW09? MYLpcohq[mm2czDic5RpKGWwZH;n[Y5wfXNiY3;ud5RqfHW2aY\lJIFv\CCLTD22MYlv\HWlZXSgV3RCXDNiYXP0bZZifGmxbh?= M4nlZ|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|NUOxPVIyLz5{M{WzNVkzOTxxYU6=
Rh18 NFTzOVFHfW6ldHnvckBCe3OjeR?= NVnTVIJ2OC53L{GuNE8zNjVxNTFOwG0> MmHBNlQhcA>? NULqNZFkTE2VTx?= MVrpcohq[mm2czDic5RpKGWwZH;n[Y5wfXNiY3;ud5RqfHW2aY\lJIFv\CCLTD22MYlv\HWlZXSgV3RCXDNiYXP0bZZifGmxbh?= NWfBV2x5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1N|E6OjFpPkKzOVMyQTJzPD;hQi=>
TC32 MnrTSpVv[3Srb36gRZN{[Xl? NGPIenoxNjVxMT6wM|IvPS93IN88US=> NF;tXVgzPCCq MkTGSG1UVw>? NInTdo1qdmirYnn0d{Bjd3SqIHXu[I9o\W6xdYOgZ49ve3SrdIX0bZZmKGGwZDDJUE03NWmwZIXj[YQhW1SDVEOgZYN1cX[jdHnvci=> NG\USm89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{WzNVkzOSd-MkO1N|E6OjF:L3G+
TPC-1 M2fzTmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NWLTOVR7OSEEtV2= MkDBNE01KGR? NE\qU5JFVVOR M2\SO4lvcGmkaYTzJINmdGxiZ4Lve5RpKGGodHXyJFIh\CC2cnXheI1mdnR? NIrPNmY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{C1OlQ6QSd-MkOwOVY1QTl:L3G+
MZ-CRC1  MlPmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MVWxJOK2VQ>? MkTKNE02KGR? MnTqSG1UVw>? NVnRPWVtcW6qaXLpeJMh[2WubDDndo94fGhiYX\0[ZIhOSCmIITy[YF1dWWwdB?= M3\BOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MEW2OFk6Lz5{M{C1OlQ6QTxxYU6=
TT  Mn;tS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MmHoNUDDvU1? M4X6V|AuPCCm NWH5XWo1TE2VTx?= NXHNTY46cW6qaXLpeJMh[2WubDDndo94fGhiYX\0[ZIhOSCmIITy[YF1dWWwdB?= NFPCfFY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{C1OlQ6QSd-MkOwOVY1QTl:L3G+
TPC-1 MonNSpVv[3Srb36gRZN{[Xl? NWTHbll[OSEEtV2= M1\GcFczKGh? NVHCRYc6TE2VTx?= NXv5UYZNcW6mdXPld{BIOSCkbH;jb4Fo\Q>? MlnVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjNyNU[0PVkoRjJ|MEW2OFk6RC:jPh?=
MZ-CRC1  M{jhfGZ2dmO2aX;uJGF{e2G7 MkfqNUDDvU1? M1zrWlczKGh? NUnpeHh7TE2VTx?= NHTtW3FqdmS3Y3XzJGcyKGKub3PrZYdm MorlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjNyNU[0PVkoRjJ|MEW2OFk6RC:jPh?=
TT  NF7LRmZHfW6ldHnvckBCe3OjeR?= NWjCR2M3OSEEtV2= NIjLN2U4OiCq M37KeGROW09? NWX5e2Y4cW6mdXPld{BIOSCkbH;jb4Fo\Q>? M4SwZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MEW2OFk6Lz5{M{C1OlQ6QTxxYU6=
MZ-CRC1  MlvGRZBweHSxc3nzJGF{e2G7 MnnUNUDDvU1? M{PY[FQ5KGh? MoHvSG1UVw>? NHTteGJqdmS3Y3XzJIFxd3C2b4Ppdy=> NFfqOlM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{C1OlQ6QSd-MkOwOVY1QTl:L3G+
TT  MnXjRZBweHSxc3nzJGF{e2G7 NFXLe4kyKML3TR?= NYW5fI9xPDhiaB?= MXvEUXNQ MYPpcoR2[2W|IHHwc5B1d3Orcx?= MljvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjNyNU[0PVkoRjJ|MEW2OFk6RC:jPh?=
HD-LM2 MYXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFTsXXc4OuLCiXi= MljGSG1UVw>? MnzuTWM2OD15Lki0OEDPxE1? NF;uUXc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkiyPVA6PCd-MkK4NlkxQTR:L3G+
L-428 NYjpXnlET3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M4HPNVcz6oDLaB?= M37GfGROW09? NIWyeXlKSzVyPUeuPVQ4KM7:TR?= MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjh{OUC5OEc,OjJ6MkmwPVQ9N2F-
KM-H2 M3PQTWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1fEUVcz6oDLaB?= MVLEUXNQ NVzvNHB4UUN3ME2xMlMxQCEQvF2= MnGyQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ6MkmwPVQoRjJ{OEK5NFk1RC:jPh?=
L-540 MnjWS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MljXO|LjiImq NU[yN5Y2TE2VTx?= NWf1d4pPUUN3ME24MlIyPiEQvF2= NV7Hc2JKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK4NlkxQTRpPkKyPFI6ODl2PD;hQi=>
HD-LM2 NVrYeJhHTnWwY4Tpc44hSXO|YYm= NWXweoNUOC5zL{CuOU8yNzVizszN MYK3NwKBkWh? M{TWcGROW09? MkjUbY5pcWKrdIOgV3RCXDNuIGPURXQ2KGGwZDDTWGFVPiCyaH;zdIhwenmuYYTpc44> NXrvdmlQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK4NlkxQTRpPkKyPFI6ODl2PD;hQi=>
L-428 MXXGeY5kfGmxbjDBd5NigQ>? NEHzc5ExNjFxMD61M|EwPSEQvF2= M4\m[Vcz6oDLaB?= M{HnW2ROW09? MnfobY5pcWKrdIOgV3RCXDNuIGPURXQ2KGGwZDDTWGFVPiCyaH;zdIhwenmuYYTpc44> NXLiPJU5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK4NlkxQTRpPkKyPFI6ODl2PD;hQi=>
KM-H2 MorOSpVv[3Srb36gRZN{[Xl? M4LkeFAvOS9yLkWvNU82KM7:TR?= MnjqO|LjiImq NEjXOIpFVVOR NUK0OnFYcW6qaXLpeJMhW1SDVEOsJHNVSVR3IHHu[EBUXEGWNjDwbI9{eGixconsZZRqd25? NFf4PJI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkiyPVA6PCd-MkK4NlkxQTR:L3G+
L-540 NW\FdXdUTnWwY4Tpc44hSXO|YYm= MUOwMlEwOC53L{GvOUDPxE1? MofLO|LjiImq M1zafGROW09? MVzpcohq[mm2czDTWGFVOyxiU2TBWFUh[W6mIGPURXQ3KHCqb4PwbI9zgWyjdHnvci=> MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjh{OUC5OEc,OjJ6MkmwPVQ9N2F-
HD-LM2 NFviPJhCeG:ydH;zbZMhSXO|YYm= NETuR3gyNzVizszN MkjjO|LjiImq NIHsTG5FVVOR M2rKbolv\HWlZYOgZZBweHSxc3nz NYOwN4Q6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkK4NlkxQTRpPkKyPFI6ODl2PD;hQi=>
L-428 MlP4RZBweHSxc3nzJGF{e2G7 NVXmXGlQOS93IN88US=> M1fIdFcz6oDLaB?= MmDaSG1UVw>? MULpcoR2[2W|IHHwc5B1d3Orcx?= M{DzXFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{OEK5NFk1Lz5{MkiyPVA6PDxxYU6=
KM-H2 NFG0dmNCeG:ydH;zbZMhSXO|YYm= MoDSNU82KM7:TR?= M4fC[lcz6oDLaB?= NGr0WHNFVVOR NIDoWpZqdmS3Y3XzJIFxd3C2b4Ppdy=> NFTNdow9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkiyPVA6PCd-MkK4NlkxQTR:L3G+
L-540 MWTBdI9xfG:|aYOgRZN{[Xl? M2PiRlEwPSEQvF2= NES0N5I4OuLCiXi= Mn;ZSG1UVw>? NIHWbYJqdmS3Y3XzJIFxd3C2b4Ppdy=> MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjh{OUC5OEc,OjJ6MkmwPVQ9N2F-
U251-MG MkLISpVv[3Srb36gRZN{[Xl? Ml3VNUDDvU1? MnzCNE0yPiCq NWTjdVhFcW6qaXLpeJMh[2:wc4TpeJV1cX[nIGPURXQuOyCjbnSgTmFMOiCjY4TpeoF1cW:w NEjTPHM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkCyO|Y6OSd-MkKwNlc3QTF:L3G+
U87-MG NH:0PIFHfW6ldHnvckBCe3OjeR?= MkSyNUDDvU1? M1TtclAuOTZiaB?= M2jxR4lvcGmkaYTzJINwdnO2aYT1eIl3\SCVVFHUMVMh[W6mIFrBT|Ih[WO2aY\heIlwdg>? NFeyW449[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkCyO|Y6OSd-MkKwNlc3QTF:L3G+
4C8 Mn;0SpVv[3Srb36gRZN{[Xl? M{ixO|EhyrWP NYr5dVJCOC1zNjDo MWTpcohq[mm2czDjc45{fGm2dYTpeoUhW1SDVD2zJIFv\CCMQVuyJIFkfGm4YYTpc44> NGTURY09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkCyO|Y6OSd-MkKwNlc3QTF:L3G+
U251-MG MXnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWexM|ExKML3TR?= M4CwO|I1NzR6L{eyJIg> MlLLbY5pcWKrdIOgZ4VtdCCycn;sbYZmemG2aX;uJIF1KGFiY3;uZ4VvfHKjdHnvckBw\iBzMDFCuW0> M{[1XFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MEK3OlkyLz5{MkCyO|Y6OTxxYU6=
U87-MG MXHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1nNUVEwOTBiwsXN NIDwOmIzPC92OD:3NkBp NEK0[YhqdmirYnn0d{Bk\WyuIIDyc4xq\mW{YYTpc44h[XRiYTDjc45k\W62cnH0bY9vKG:oIEGwJOK2VQ>? NYXwRmhMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKwNlc3QTFpPkKyNFI4PjlzPD;hQi=>
4C8 NX7L[JF7T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NX\Tb4tDOS9zMDFCuW0> MnfuNlQwPDhxN{KgbC=> MoXIbY5pcWKrdIOgZ4VtdCCycn;sbYZmemG2aX;uJIF1KGFiY3;uZ4VvfHKjdHnvckBw\iBzMDFCuW0> MojNQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJyMke2PVEoRjJ{MEK3OlkyRC:jPh?=
U266 NUXaT|V7SXCxcITvd4l{KEG|c3H5 MWmwMlUuOiEQvF2= NF;1W4s1QC95MjDo MYHpcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF4NEWxO{c,OjFzNkS1NVc9N2F-
Kms.11 M4jIe2Fxd3C2b4Ppd{BCe3OjeR?= MnvHNE42NTJizszN MUG0PE84OiCq M3\GbIlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm= MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF4NEWxO{c,OjFzNkS1NVc9N2F-
8226 M2\acWFxd3C2b4Ppd{BCe3OjeR?= NE\QdYgxNjVvMjFOwG0> Ml6wOFgwPzJiaB?= MYPpcoR2[2W|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7 M{Czc|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMU[0OVE4Lz5{MUG2OFUyPzxxYU6=
SET2 MUPHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? M3LPRlQ5KGi{cx?= NXmxO2FVT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hW0WWMjDj[YxteyCneIDy[ZN{cW6pIFrhb|IhXjZzN1[gcZV1[W62IHHmeIVzKDR6IHjyd{BjgSCPVGOgZZN{[XluIFfJOVAhRSByLkCxOkDPxE1w M4jaTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
SET2 MlLzSpVv[3Srb36gZZN{[Xl? NI\BTXQyKGi{ NYHaZ3lOUW6qaXLpeIlwdiCxZjDTeIF1OyCyaH;zdIhwenmuYYTpc44hcW5iaIXtZY4hW0WWMjDj[YxteyCjZoTldkAyKGi{IHL5JHdme3Sncn6gZoxwfHSrbnesJGlEPTBiPTCwMlAzOyEQvF2u MlPEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzM{iyOFYoRjJzMUO4NlQ3RC:jPh?=
SET2 NGTzO2lHfW6ldHnvckBie3OjeR?= MWKxJIhz MmG2TY5pcWKrdHnvckBw\iCVdHH0OUBxcG:|cHjvdplt[XSrb36gbY4hcHWvYX6gV2VVOiClZXzsd{Bi\nSncjCxJIhzKGK7IGfld5Rmem5iYnzveJRqdmduIFnDOVAhRSByLkCyOUDPxE1w Ml34QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzM{iyOFYoRjJzMUO4NlQ3RC:jPh?=
HEL NX7UZ45FTnWwY4Tpc44h[XO|YYm= NGTLRm4yKGi{ MnXSTY5pcWKrdHnvckBw\iCVdHH0OUBxcG:|cHjvdplt[XSrb36gbY4hcHWvYX6gTGVNKGOnbHzzJIFnfGW{IEGgbJIh[nliV3XzeIVzdiCkbH;0eIlv\yxiSVO1NEA:KDBwMESxJO69VS5? MmnoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzM{iyOFYoRjJzMUO4NlQ3RC:jPh?=
Ba/F3 MXPGeY5kfGmxbjDhd5NigQ>? NV7F[|dCUW6qaXLpeIlwdiCxZjDTeIF1PSCyaH;zdIhwenmuYYTpc44hcW5ibX;1d4UhSmFxRkOgZ4VtdHNiZYjwdoV{e2mwZzDUSWwuUmGtMjygTWM2OCB;IECuNFQ3KM7:TT6= MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF|OEK0Okc,OjFzM{iyOFY9N2F-
UKE1 M3Ltdmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NEG0SVM1QCCqcoO= NYjKUY1ST3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hXUuHMTDj[YxteyCneIDy[ZN{cW6pIFrhb|IhXjZzN1[gcZV1[W62IHHmeIVzKDR6IHjyd{BjgSCPVGOgZZN{[XluIFfJOVAhRSByLkC1OEDPxE1w NH7nb3k9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUGzPFI1Pid-MkGxN|gzPDZ:L3G+
BA/F3 M2XwSWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 M{fYb|Q5KGi{cx?= Mo\BS5Jwf3SqIHnubIljcXSrb36gc4YhdW:3c3WgRmEwTjNiY3XscJMh\XiycnXzd4lv\yCWZXytTmFMOiCtaX7hd4Uh[W[2ZYKgOFghcHK|IHL5JG1VWyCjc4PhfUwhT0l3MDC9JFAvODZizszNMi=> NV;ifJdTRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxN|gzPDZpPkKxNVM5OjR4PD;hQi=>
HEL NW\3dYpWTnWwY4Tpc44h[XO|YYm= MUixJIhz M1qwemlvcGmkaYTpc44hd2ZiU4TheFMheGixc4Doc5J6dGG2aX;uJIlvKGi3bXHuJGhGVCClZXzsd{Bi\nSncjCxJIhzKGK7IGfld5Rmem5iYnzveJRqdmduIFnDOVAhRSByLkC4JO69VS5? MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF|OEK0Okc,OjFzM{iyOFY9N2F-
HEL Mlj4S5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? M362ZVQ5KGi{cx?= NUTDUolZT3Kxd4ToJIlvcGmkaYTpc44hd2ZiaIXtZY4hUEWOIHPlcIx{KGW6cILld5NqdmdiSnHrNkBXPjF5RjDteZRidnRiYX\0[ZIhPDhiaILzJIJ6KE2WUzDhd5NigSxiR1m1NEA:KDBwM{mg{txONg>? NV:xT3NVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxN|gzPDZpPkKxNVM5OjR4PD;hQi=>
BA/F3 MXjHdo94fGhiaX7obYJqfGmxbjDhd5NigQ>? NYLqSoNSPDhiaILz NHSzfIFIem:5dHigbY5pcWKrdHnvckBw\iCvb4Xz[UBDSS:IMzDj[YxteyCneIDy[ZN{cW6pIGTlcE1LSUtzIHvpcoF{\SCjZoTldkA1QCCqcoOgZpkhVVSVIHHzd4F6NCCJSUWwJF0hOC55IN88UU4> MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF|OEK0Okc,OjFzM{iyOFY9N2F-
BA/F3 M3PJdGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MoXCOFghcHK| M1L5fGdzd3e2aDDpcohq[mm2aX;uJI9nKG2xdYPlJGJCN0Z|IHPlcIx{KGW6cILld5NqdmdiVHXsMXR6czJia3nuZZNmKGGodHXyJFQ5KGi{czDifUBOXFNiYYPzZZktKEeLNUCgQUAzKM7:TT6= MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF|OEK0Okc,OjFzM{iyOFY9N2F-
BA/F3 M1PJcWdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MkDvOFghcHK| NU\wWHN1T3Kxd4ToJIlvcGmkaYTpc44hd2ZibX;1d4UhSkFxRkOgZ4VtdHNiZYjwdoV{e2mwZzDU[YwuUkGNMzDrbY5ie2ViYX\0[ZIhPDhiaILzJIJ6KE2WUzDhd5NigSxiR1m1NEA:KDJwMTFOwG0v MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF|OEK0Okc,OjFzM{iyOFY9N2F-
UKE1 NYeybXBITnWwY4Tpc44h[XO|YYm= M4rEeFEhcHJ? M1HQSmlvcGmkaYTpc44hd2ZiU4TheFUheGixc4Doc5J6dGG2aX;uJIlvKGi3bXHuJHVMTTFiY3XscJMh[W[2ZYKgNUBpeiCkeTDX[ZN1\XKwIHLsc5R1cW6p MnLEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzM{iyOFYoRjJzMUO4NlQ3RC:jPh?=
SW620 M1iwTmNmdGxiY4njcIUh[XO|YYm= NFXncIs{NjNidV2= MoDtNlQhcHK| M3K5OmNmdGxiY4njcIUh[XK{ZYP0JIlvKGi3bXHuJHNYPjJyIHPlcIx{KGG|c3Xzd4VlKGG|IHHjZ5VufWyjdHnvckBifCCJMj;NJJBp[XOnIHH0JFMvOyC3TTDh[pRmeiB{NDDodpMh[nliZnzve{BkgXSxbXX0dpk> NX6zNJJGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxN|gzPDZpPkKxNVM5OjR4PD;hQi=>
HEL MX\GeY5kfGmxbjDhd5NigQ>? M4LtV|AvOyC3TR?= MWK1JI1qdnN? MlnaTY5pcWKrdHnvckBw\iCVdHH0OUBxcG:|cHjvdplt[XSrb36gbY4hcHWvYX6gTGVNKGOnbHzzJIF1KDBwMzD1UUBi\nSncjC1JI1qdnNiYomgW4V{fGW{bjDicI91fGmwZx?= M1TmbFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
HEL NFrOTVZHfW6ldHnvckBie3OjeR?= MWiwMlMhfU1? MYmzNEB1dyB4MDDtbY5{ MWfJcohq[mm2aX;uJI9nKFO2YYS1JJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDISWwh[2WubIOgZZQhOC5|IIXNJIFnfGW{IEOwJJRwKDZyIH3pcpMh[nliV3XzeIVzdiCkbH;0eIlv\w>? MkKwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzM{iyOFYoRjJzMUO4NlQ3RC:jPh?=
BA/F3 MVvBcpRqfHWvb4KgZZN{[Xl? MkjvN|AhdWdxa3e= Mk\5NVIhcHK| NF3lWpdCdnSrdIXtc5Ih[WO2aY\peJkh[WejaX7zeEBud3W|ZTDCRU9HOyClZXzsd{BmgHC{ZYPzbY5oKFSnbD3KRWszKHinbn;ndoFnfGWmIHnuJG5EeiCvb4Xz[UBie3Onc4Pl[EBieyC{ZXT1Z5Rqd25ib3[gdIhwe3Cqb4L5cIF1\WRiU4TheFUhdGW4ZXygbY4he3CuZXXuJIF1KDNyIH3nM4toNCCybzDh[pRmeiBzMjDodpMh[nliV3XzeIVzdiCkbH;0eIlv\w>? M3rkVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUO4NlQ3Lz5{MUGzPFI1PjxxYU6=
HEL NV;RbJprTnWwY4Tpc44h[XO|YYm= MW[wMlMhfU1? MVO1JI1qdnN? NV;ZO49jUW6qaXLpeIlwdiCxZjDTeIF1OyCyaH;zdIhwenmuYYTpc44hcW5iaIXtZY4hUEWOIHPlcIx{KGG2IECuN{B2VSCjZoTldkA2KG2rboOgZpkhX2W|dHXyckBjdG:2dHnu[y=> MlvMQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzM{iyOFYoRjJzMUO4NlQ3RC:jPh?=
HEL NIHY[oVHfW6ldHnvckBie3OjeR?= NF3TPHUxNjNidV2= MVuzNEB1dyB4MDDtbY5{ MX;Jcohq[mm2aX;uJI9nKFO2YYSzJJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDISWwh[2WubIOgZZQhOC5|IIXNJIFnfGW{IEOwJJRwKDZyIH3pcpMh[nliV3XzeIVzdiCkbH;0eIlv\w>? MX:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF|OEK0Okc,OjFzM{iyOFY9N2F-
Hs578T NHHx[4RHfW6ldHnvckBie3OjeR?= M2frZ|EhfU1? NX6yNG1{OjRiaILz NHrZd3ZKdmirYnn0bY9vKG:oIGPURXQ{Sy2vZXTpZZRm\CC2cnHud4NzcXC2aX;uJIlvKGi3bXHuJGh{PTd6VDDj[YxteyCjdDCxJJVOKGGodHXyJFI1KGi{czDifUBtfWOrZnXyZZNmKHKncH;yeIVzKGenbnWgZZN{[Xl? NUWzWnBKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5O|gyOTJpPkK0PVc5OTF{PD;hQi=>
NCI-H1975 M{H0dWZ2dmO2aX;uJIF{e2G7 MWWwMlAxOyC2bzCzJJVO NELnOWIzKGi{cx?= MV3Jcohq[mm2aX;uJI9nKEqDS{GgbY4hcHWvYX6gUmNKNUhzOUe1JINmdGy|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBqdiCVVFHUN{BxcG:|cHjvdplt[XSrb36gZZQhOC5yMEOgeI8hOyC3TTDh[pRmeiB{IHjyd{BjgSCZZYP0[ZJvKGKub4SgZY5idHm|aYO= M2TadlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NkG0OFA5Lz5{Nk[xOFQxQDxxYU6=
HEL 92.1.7 MknySpVv[3Srb36gZZN{[Xl? MVKyJIhzew>? NXftV5FKUW6qaXLpeIlwdiCxZjDKRWszKGmwIHj1cYFvKEiHTDC5Nk4yNjdiY3XscJMh[XO|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJHNVSVR3IIDoc5NxcG:{eXzheIlwdiCjZoTldkAzKGi{czDifUBY\XO2ZYLuJIJtd3RiYX7hcJl{cXN? M2nKXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4NkG0OFA5Lz5{Nk[xOFQxQDxxYU6=
DAOY MWrxTHRUKGG|c3H5 NF3TcVlyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiRFHPXUBk\Wyucx?= NH[1dJA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
SJ-GBM2 M2jhNpFJXFNiYYPzZZk> MYfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0pvR1LNNkBk\Wyucx?= MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
A673 MV;xTHRUKGG|c3H5 MWnxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW|IH\vdkBlenWpIILldJVzeG:|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSTZ5MzDj[Yxtew>? NVzTVWtkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N|UyOzlpPkK5OFM2OTN7PD;hQi=>
SK-N-MC MVjxTHRUKGG|c3H5 NY\oR4o4eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPLMW4uVUNiY3XscJM> MlPUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
BT-37 MYnxTHRUKGG|c3H5 M2rLfJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCEVD2zO{Bk\Wyucx?= MlXxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
NB-EBc1 M3nJXpFJXFNiYYPzZZk> Ml;idWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKE6ELVXCZ|Eh[2WubIO= NFTp[nA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N|UyOzl:L3G+
Saos-2 NFX1ToNyUFSVIHHzd4F6 NYrLTIdneUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPhc5MuOiClZXzsdy=> M3ntTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-SH M1;UT5FJXFNiYYPzZZk> NYHRUYpHeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC|Y4Ll[Y4h\m:{IGPLMW4uW0hiY3XscJM> MojYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
NB1643 MXfxTHRUKGG|c3H5 NGPsPIdyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKxOlQ{KGOnbHzz M{DmNVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
BT-12 MlvydWhVWyCjc4PhfS=> MmfydWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKEKWLUGyJINmdGy| Mlv0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
OHS-50 NIX1RWZyUFSVIHHzd4F6 M4XsdpFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCRSGOtOVAh[2WubIO= MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
RD MkjDdWhVWyCjc4PhfS=> M1XNVZFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCURDDj[Yxtew>? M{DCVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
MG 63 (6-TG R) MYnxTHRUKGG|c3H5 Mln1dWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[|ohWHKrbXHyfUB{[3KnZX6g[o9zKE2JIE[zJEg3NVSJIGKpJINmdGy| MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
Rh41 M1P3WpFJXFNiYYPzZZk> M1LTZ5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCUaESxJINmdGy| Mof3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN|koRjJ7NEO1NVM6RC:jPh?=
Assay
Methods Test Index PMID
Western blot p-STAT3 / STAT3 / p-JAK2 / JAK2 ; p-STAT1 / STAT1 / p-STAT5 / STAT5 / p-STAT6 / STAT6 ; p-ERK / ERK / p-p38 / p38 / SOCS3 / p-SHP2 / SHP2 22027691 22829094
Immunofluorescence pSTAT5 30140255
Growth inhibition assay Cell proliferation ; Cell viability 22027691 25855603
In vivo AZD1480 inhibits the STAT3 phosphorylation in an xenograft model of human solid tumors and multiple myeloma. [1] In vivo, AZD1480 inhibits the growth of subcutaneous tumors and increases survival of mice bearing intracranial glioblastoma (GBM) tumors by inhibiting STAT-3 activity, indicating that pharmacologic inhibition of the JAK/STAT-3 pathway by AZD1480 should be considered for study in the treatment of patients with GBM tumors. [3]AZD1480 blocks lung infiltration of myeloid cells and formation of pulmonary metastases in both mouse syngeneic experimental and spontaneous metastatic models. Furthermore, AZD1480 reduces angiogenesis and metastasis in a human xenograft tumor model. [4] The Jak2 inhibitor, AZD1480, suppresses the growth of human solid tumor xenografts harboring persistent Stat3 activity. [5]

Protocol (from reference)

Kinase Assay:[5]
  • kinase assays:

    Inhibition studies of AZD1480 are performed using recombinant Jak1, Jak2, or Jak3 under buffer conditions of 50 mM HEPES pH 7.3, 1 mM DTT, 0.01% Tween-20, 50 mM/ml BSA, and 10 mM MgCl2. Jak3 enzyme is expressed as N-terminal GST fusion in insect cells and purified by glutathione-affinity and size-exclusion chromatographies. Enzymes are assayed in the presence of AZD1480 (10 point dose response, in triplicate, from 8.3 μM to 0.3 nM in half-log dilution steps) using 1.5 μM peptide substrate (Jak1: FITC-C6-KKHTDDGYMPMSPGVA-NH2, Jak2 and Jak3: FAM-SRCtide) and screened under their respective ATP Km (Jak1: 55 μM, Jak2: 15 μM, Jak3: 3 μM) and approximated physiological ATP concentration of 5 mM. Phosphorylated and unphosphorylated peptides are separated and quantified by a Caliper LC3000 system for calculating percent inhibition.

Cell Research:[4]
  • Cell lines: Renca or 786-O cells, mouse endothelial cells and splenic CD11b+/c-myeloid cells, HUVECs
  • Concentrations: ~1 μM
  • Incubation Time: 48 or 24 hours
  • Method: Renca or 786-O cells are suspended in DMEM medium with 5% FBS , and seeded in 96-well plates (5×103 per well) to allow adhesion and then treated with DMSO or AZD1480 for 48 hours. Cell viability is determined by MTS assay. Absorbance at 490 nm is measured with Mikrotek Laborsysteme. Mouse endothelial cells and splenic CD11b+/c- myeloid cells are enriched from tumor-bearing mice,and cultured in 5% FBS RPMI-1640 medium. HUVECs are cultured on collagen 1–coated plates in complete medium. All cells are treated with DMSO and AZD1480 at various doses for 24 hours. Cell viability is determined by counting cell number manually. All the experiments are repeated 3 times.
  • (Only for Reference)
Animal Research:[4]
  • Animal Models: Female BALB/c and athymic nude (NCR - nu/nu) mice (7–8 weeks old)
  • Dosages: Once a day at the dose of 50 mg/kg or twice daily at 30 mg/kg
  • Administration: Oral gavage
  • (Only for Reference)

Solubility (25°C)

In vitro

DMSO 69 mg/mL warmed
(197.83 mM)
Water Insoluble
Ethanol Insoluble

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
30% PEG400+0.5% Tween80+5% propylene glycol
For best results, use promptly after mixing.

5 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 348.77
Formula

C14H14ClFN8

CAS No. 935666-88-9
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=CC(=NN1)NC2=NC(=NC=C2Cl)NC(C)C3=NC=C(C=N3)F

In vivo Formulation Calculator (Clear solution)

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

mg/kg g μL

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

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

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

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

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

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

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

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

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy AZD1480|AZD1480 ic50|AZD1480 price|AZD1480 cost|AZD1480 solubility dmso|AZD1480 purchase|AZD1480 manufacturer|AZD1480 research buy|AZD1480 order|AZD1480 mouse|AZD1480 chemical structure|AZD1480 mw|AZD1480 molecular weight|AZD1480 datasheet|AZD1480 supplier|AZD1480 in vitro|AZD1480 cell line|AZD1480 concentration|AZD1480 nmr|AZD1480 in vivo|AZD1480 clinical trial|AZD1480 inhibitor|AZD1480 JAK/STAT inhibitor