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Tofacitinib (CP-690550)

Name: Tofacitinib (CP-690550)
Brand: Selleck Chemicals
SKU: S2789
Rating: 5 (136 reviews)

Licensed by Pfizer Catalog No.S2789 Synonyms: Tasocitinib

For research use only.

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

Tofacitinib (CP-690550) Chemical Structure

CAS No. 477600-75-2

Selleck's Tofacitinib (CP-690550) has been cited by 136 publications

Purity & Quality Control

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JAK Signaling Pathway Map

Biological Activity

Description

Targets

JAK3 ^[1] (Cell-free assay)	JAK2 ^[1] (Cell-free assay)	JAK1 ^[1] (Cell-free assay)
1 nM	20 nM	112 nM

In vitro

CP-690550 is a specific, orally inhibitor of JAK3, it is 20- to 100-fold less potent for JAK2 and JAK1 with IC50 of 20 nM and 112 nM, respectively. CP-690550 doesn't have potent activity against 30 other kinases (all median IC50 > 3000 nM). CP-690,550 inhibits IL-2–induced proliferation with 30-fold greater potency than its effects on GM-CSF–induced proliferation. ^[1] CP-690550 effectively inhibits a murine mixed lymphocyte reaction (MLR) (IC50 = 91 nM). ^[2] CP-690550 potently inhibits IL-4 induced upregulation of CD23 (IC50=57 nM) and class II major histocompatibility complex (MHCII) expression (IC50=71 nM) on murine B cells. ^[3] A recent research indicates low dose of CP-690550 accelerates the onset of experimental autoimmune encephalomyelitis by potentiating Th17 differentiation. ^[4]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID

T cells	M1P5cGZ2dmO2aX;uJGF{e2G7	MmnxNE4yNzBwMz:xJO69VQ>?	M3TXcVI1KGh?	NVj5emt[\Gm\|coXweJMh\|rOlLXPoZYlvKGO7dH;rbY5mKHOrZ37hcIlv\w>?	MlryQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF\|OEOyOFEoRjJzM{izNlQyRC:jPh?=
CD4+ T	MYPGeY5kfGmxbjDBd5NigQ>?	M3njXVExOCCwTR?=	M1znb\|I1NzR6IHi=	MXzhZpJw\2G2ZYOgR2Q{NWmwZIXj[YQheGixc4Doc5J6dGG2aX;uJI9nKFOWQWTz	M2f2XFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOEi0OVgxLz5{MUi4OFU5ODxxYU6=
CD4+ T	M1XQSWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MmTxNVAxNzVyMDDuUS=>	NX64NXk4PDhiaB?=	NUnUeHkxcW6qaXLpeJMh[W62aT3DSFMucW6mdXPl[EBETDRtwrDUJINmdGxicILvcIln\XKjdHnvci=>	Mo\CQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF6OES1PFAoRjJzOEi0OVgxRC:jPh?=
CD4+ T	MV7GeY5kfGmxbjDBd5NigQ>?	NH;UUoUzOC9zMECvOVAxKG6P	MoDTOFghcA>?	MkTqbY5pcWKrdIOgeIhmKGyndnXsd{Bw\iBiSVytOEwhUU[QLd8zMEBKVC1zN1GgZY5lKEmOLUKy	Mn\wQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF6OES1PFAoRjJzOEi0OVgxRC:jPh?=
Sf9	M3ftV2Z2dmO2aX;uJIF{e2G7		M121TVMxKG2rboO=	NVvnWlNyUW6qaXLpeIlwdiCxZjDoeY1idiCJU2St[pV{\WRiSlHLN{Bk[XSjbIn0bYMh\G:vYXnuJIV5eHKnc4Pl[EBqdiCkYXP1cI93cXK3cz3pcoZm[3SnZDDT[lkh[2WubIOgeZNqdmdicH;sfYdtfXSjbXnjJIFkcWRvdInyc5NqdmViYYOgd5Vje3S{YYTlJIFnfGW{IEOwJI1qdnNiYomgSWxKW0FuIFvpJF0hOC5yMEC0JO69VS5?	MnfjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN4Nki0PFQoRjJ\|Nk[4OFg1RC:jPh?=
Sf9	MVPGeY5kfGmxbjDhd5NigQ>?		M{j4R\|kxKG2rboO=	MlnKTY5pcWKrdHnvckBw\iCqdX3hckBz\WOxbXLpcoFvfCCQLYTldo1qdmGuIFfTWE11[WepZXSgTmFMOyCneIDy[ZN{\WRiaX6gV4Y6KGOnbHzzJJV{cW6pIFLpc5Rqdi2OQz3FVWVFTVCHR1TZSmVYVEViYYOgd5Vje3S{YYTlJIFnfGW{IEmwJI1qdnNiYomgWHIuTlKHVDDhd5NigSxiSVO1NEA:KDBwMECwOkDPxE1w	MoriQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJyOEe3OVAoRjJ{MEi3O\|UxRC:jPh?=
Sf9	MXvGeY5kfGmxbjDhd5NigQ>?		MUWzNEBucW6\|	NV6xfG1pUW6qaXLpeIlwdiCxZjDoeY1idiCJU2St[pV{\WRiSlHLNUBk[XSjbIn0bYMh\G:vYXnuJIV5eHKnc4Pl[EBqdiCkYXP1cI93cXK3cz3pcoZm[3SnZDDT[lkh[2WubIOgeZNqdmdicH;sfYdtfXSjbXnjJIFkcWRvdInyc5NqdmViYYOgd5Vje3S{YYTlJIFnfGW{IEOwJI1qdnNiYomgSWxKW0FuIFvpJF0hOC5yMEC3JO69VS5?	MnPzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN4Nki0PFQoRjJ\|Nk[4OFg1RC:jPh?=
Sf9	NHXae2ZHfW6ldHnvckBie3OjeR?=		NVu1T5p1OzBibXnudy=>	MmfuTY5pcWKrdHnvckBw\iCqdX3hckBIW1RvZoXz[YQhUkGNMjDjZZRidHm2aXOg[I9u[WmwIHX4dJJme3OnZDDpckBj[WO3bH;2bZJ2ey2rbn\lZ5Rm\CCVZkmgZ4VtdHNidYPpcocheG:ueXfseZRidWmlIHHjbYQufHm{b4PpcoUh[XNic4Xid5Rz[XSnIHHmeIVzKDNyIH3pcpMh[nliRVzJV2EtKEurIE2gNE4xODB5IN88UU4>	MWO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzZ4OES4OEc,OjN4Nki0PFQ9N2F-
Sf9	Mo\wSpVv[3Srb36gZZN{[Xl?			M{[zdmlvcGmkaYTpc44hd2ZiaIXtZY4hemWlb33ibY5idnRiR2PUMZRi\2enZDDKTFEh\G:vYXnuJEg4QDVidH:xNVI2MSCxZjDKRWs{KGW6cILld5Nm\CCrbjDpcpNm[3RiU3[5JINmdGy\|IHL5JGVNUVODLDDJR\|UxKD1iMD6wNFEh\|ryPLh?=	MnzNQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTR3OUOxPFIoRjF2NUmzNVgzRC:jPh?=
Sf9	MYHGeY5kfGmxbjDhd5NigQ>?			NFnhV49KdmirYnn0bY9vKG:oIFfTWE11[WepZXSgbJVu[W5iSlHLN{Bk[XSjbIn0bYMh\G:vYXnuJIV5eHKnc4Pl[EBqdiCVZkmgZ4VtdHNiYomgSWxKW0FuIFnDOVAhRSByLkCwNUDPxE1w	NWf2dpNmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxNFU4OTFpPkKxNVA2PzFzPD;hQi=>
Sf9	NUPBNVVPTnWwY4Tpc44h[XO\|YYm=		NUDDOY5GQTBibXnudy=>	MWDJcohq[mm2aX;uJI9nKGi3bXHuJJJm[2:vYnnuZY51KE5vdHXycYlv[WxiR2PUMZRi\2enZDDKRWsyKGW6cILld5Nm\CCrbjDT[lkh[2WubIOgeZNqdmdiQnnveIlvNUyFLVXRSWRGWEWJRGnGSXdNTSCjczDzeYJ{fHKjdHWgZYZ1\XJiOUCgcYlveyCkeTDUVk1HWkWWIHHzd4F6NCCLQ{WwJF0hOC5yMEOg{txONg>?	MmnpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJyOEe3OVAoRjJ{MEi3O\|UxRC:jPh?=
Sf9	Mn7qSpVv[3Srb36gZZN{[Xl?			MmnVTY5pcWKrdHnvckBw\iCJU2SteIFo\2WmIHj1cYFvKEqDS{OgZ4F1[Wy7dHnjJIRwdWGrbjDlfJBz\XO\|ZXSgbY4hW2Z7IHPlcIx{KGK7IFXMTXNCNCCLQ{WwJF0hOC5yMEOzJO69VS5?	MkjOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzMEW3NVEoRjJzMUC1O\|EyRC:jPh?=
Sf9	MVjGeY5kfGmxbjDhd5NigQ>?		MkTUPVAhdWmwcx?=	MXTJcohq[mm2aX;uJI9nKGi3bXHuJJJm[2:vYnnuZY51KE5vdHXycYlv[WxiR2PUMZRi\2enZDDKRWszKGW6cILld5Nm\CCrbjDT[lkh[2WubIOgeZNqdmdiQnnveIlvNUyFLVXRSWRGWEWJRGnGSXdNTSCjczDzeYJ{fHKjdHWgZYZ1\XJiOUCgcYlveyCkeTDUVk1HWkWWIHHzd4F6NCCLQ{WwJF0hOC5yMESg{txONg>?	NYnTXlBjRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKwPFc4PTBpPkKyNFg4PzVyPD;hQi=>
SF21	NETrR21HfW6ldHnvckBie3OjeR?=		M4P0bFExKG2rboO=	NVX5XYp3UW6qaXLpeIlwdiCxZjDKRWszKCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIGPGNlEh[2WubIOgeZNqdmdiQnnveIlvNUuDSVXUSGtGYVmWVlvEJIF{KHO3YoP0doF1\SCjbnSgX\|M{WGejbX3hYWFVWCCrbnP1ZoF1\WRiZn;yJFExKG2rboOgdJJqd3JidH:gd5Vje3S{YYTlJIFl\Gm2aX;uJI1m[XO3cnXkJIFnfGW{IEOwJI1qdnNiYomgWI9x[2:3boSgZY5idHm\|aYOsJGlEPTBiPTCwMlAxPCEQvF2u	NIX6eGY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{W0NVY4OCd-MkO1OFE3PzB:L3G+
insect cells	NVrqbGROTnWwY4Tpc44h[XO\|YYm=			M1\vTWlvcGmkaYTpc44hd2ZiR2PUMZRi\2enZDDKZYsyKGW6cILld5Nm\CCrbjDpcpNm[3RiY3XscJMhfXOrbnegO\|AhfU1iQWTQMEBKSzVyIE2gNE4xODZzIN88UU4>	NFzXemc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUG1OVYxPSd-MkGxOVU3ODV:L3G+
insect cells	NVjWO5g6TnWwY4Tpc44h[XO\|YYm=			NWLoVG9WUW6qaXLpeIlwdiCxZjDHV3QufGGpZ3XkJGpiczNiZYjwdoV{e2WmIHnuJIlve2WldDDj[YxteyC3c3nu[{AyQCC3TTDBWHAtKEmFNUCgQUAxNjByODFOwG0v	NYC5Vm85RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxOVU3ODVpPkKxNVU2PjB3PD;hQi=>
T-cells	M4O4RWZ2dmO2aX;uJIF{e2G7		NWnQfYl6PzJiaILz	NGezPHhKdmirYnn0bY9vKG:oIFnMNk1qdmS3Y3XkJJBzd2yrZnXyZZRqd25ib3[gbJVu[W5iVDDj[YxteyCjc4Pld5Nm\CCjczDbN2hefGi7bXnkbY5mKGmwY3;ydI9z[XSrb36gZYZ1\XJiN{KgbJJ{KGK7IIPjbY51cWyuYYTpc44h[2:3boTpcoctKEmFNUCgQUAxNjBzMTFOwG0v	MV:8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPDV7M{G4Nkc,OTR3OUOxPFI9N2F-
insect cells	NHjwVlJHfW6ldHnvckBie3OjeR?=			M3;KO2lvcGmkaYTpc44hd2ZiR2PUMZRi\2enZDDKZYszKGW6cILld5Nm\CCrbjDpcpNm[3RiY3XscJMhfXOrbnegNlAhfU1iQWTQMEBKSzVyIE2gNE4xOTJizszNMi=>	NFSxTmE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUG1OVYxPSd-MkGxOVU3ODV:L3G+
MO7	NY\MNVliTnWwY4Tpc44h[XO\|YYm=			MXjJcohq[mm2aX;uJI9nKEqja{OtcYVlcWG2ZXSgTWwyPS2rbnT1Z4VlKFO2YYS1JJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDNU\|ch[2WubIOgZpkh[2WubD3iZZNm\CCjc4PhfUwhUUN3MDC9JFAvODJ2IN88UU4>	MnjUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzNUW2NFUoRjJzMUW1OlA2RC:jPh?=
Ba/F3	M2TB[WZ2dmO2aX;uJIF{e2G7		M3zDWlYxKG2rboO=	MkLITY5pcWKrdHnvckBw\iCWRVyt[pV{\WRiSlHLNUBmgHC{ZYPz[YQhcW5iQnGvSlMh[2WubIOgZZN{\XO\|ZXSgZZMhcW6qaXLpeIlwdiCxZjDTWGFVPSCyaH;zdIhwenmuYYTpc44h[W[2ZYKgOlAhdWmwczDifUBCdHCqYWPjdoVmdiCjc4PhfUwhUUN3MDC9JFAvODJ4IN88UU4>	M1uyW\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MEi3O\|UxLz5{MkC4O\|c2ODxxYU6=
T-cells	MUfGeY5kfGmxbjDhd5NigQ>?			MYjJcohq[mm2aX;uJI9nKEqDS{OvNUBqdiCqdX3hckBVKGOnbHzzJIV5eHKnc4PpcochS0R\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiSVyyMZN1cW23bHH0[YQhW1SDVEXhJJBpd3OyaH;yfYxifGmxbjygTWM2OCB;IECuNFI5KM7:TT6=	NGjLbWg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{W0NFY1QCd-MkO1OFA3PDh:L3G+
PBMC	MVPGeY5kfGmxbjDhd5NigQ>?			MXrJcohq[mm2aX;uJGlNNTdvaX7kZ5Vm\CCVVFHUOUBxcG:\|cHjvdplt[XSrb36gbY4hcHWvYX6gVGJOSyClZXzsd{BjgSCobH;3JIN6fG:vZYTyfUwhUUN3MDC9JFAvODN7IN88UU4>	MonOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ7Mke0NlMoRjJ4OUK3OFI{RC:jPh?=
TF1	NUj2cVI{TnWwY4Tpc44h[XO\|YYm=		NWfIcGs5OjBibXnudy=>	MWnJcohq[mm2aX;uJI9nKEqDS{GgbY4hcHWvYX6gWGYyKGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gTWw3NWmwZIXj[YQhW1SDVEOgdIhwe3Cqb4L5cIF1cW:wIHnuZ5Vj[XSnZDDmc5IhOjBibXnud{Bnd2yub4fl[EBjgSCLTE[gZ4hidGynbnflJIZweiB\|MDDtbY5{KGmwIIDy[ZNmdmOnIH;mJJdpd2ynIHLsc49lNCCHQ{WwJF0hOC5yNEOg{txONg>?	M{XkfVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NkW5NlE1Lz5{M{[1PVIyPDxxYU6=
TF1	NET4OHdHfW6ldHnvckBie3OjeR?=			MY\Jcohq[mm2aX;uJI9nKEqDS{GgbY4hcHWvYX6gWGYyKGOnbHzzJIF{e2W\|c3XkJIF{KHO3cIDy[ZN{cW:wIH;mJGlNPi2\|dHnteYxifGWmIGPURXQ{KHCqb4PwbI9zgWyjdHnvckBjgSCDbIDoZXNkemWnbjDhd5NigSxiSV7IJF0hOC5yNEWg{txONg>?	M2X6O\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4M{eyOlU{Lz5{NkO3NlY2OzxxYU6=
CTLL	MXrGeY5kfGmxbjDhd5NigQ>?			NX\OT\|g6UW6qaXLpeIlwdiCxZjDKZYs{NW2nZHnheIVlKEmOMj3pcoR2[2WmIGP0ZZQ2KHCqb4PwbI9zgWyjdHnvckBqdiCvb4Xz[UBEXEyOIHPlcIx{KGK7IHPlcIwu[mG\|ZXSgZZN{[XluIFnDOVAhRSByLkC0PEDPxE1w	M2[0flxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUW1OlA2Lz5{MUG1OVYxPTxxYU6=
Sf9	NGDYV4dHfW6ldHnvckBie3OjeR?=		MoftPVAhdWmwcx?=	MlTwTY5pcWKrdHnvckBw\iCqdX3hckBz\WOxbXLpcoFvfCCQLYTldo1qdmGuIFfTWE11[WepZXSgWHlMOiCneIDy[ZN{\WRiaX6gV4Y6KGOnbHzzJJV{cW6pIFLpc5Rqdi2OQz3FVWVFTVCHR1TZSmVYVEViYYOgd5Vje3S{YYTlJIFnfGW{IEmwJI1qdnNiYomgWHIuTlKHVDDhd5NigSxiSVO1NEA:KDBwMEWyJO69VS5?	NVzzcVhJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKwPFc4PTBpPkKyNFg4PzVyPD;hQi=>
TF1	M2WyemZ2dmO2aX;uJIF{e2G7			MV;Jcohq[mm2aX;uJI9nKEqDS{GgbY4hcHWvYX6gWGYyKGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gTWwzNWmwZIXj[YQhW1SDVEOgdIhwe3Cqb4L5cIF1cW:wLDDFR\|UxKD1iMD6wOVMh\|ryPLh?=	MoLCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ3OUG0NFIoRjJ{NUmxOFAzRC:jPh?=
TF1	NXPx[5Q4TnWwY4Tpc44h[XO\|YYm=		MUGyNEBucW6\|	NXfOeHE1UW6qaXLpeIlwdiCxZjDKRWsyKGmwIHj1cYFvKFSIMTDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKEmONj3pcoR2[2WmIGPURXQ{KHCqb4PwbI9zgWyjdHnvckBqdmO3YnH0[YQh\m:{IEKwJI1qdnNicILpc5IhfG9iSVy2MYlv\HWldHnvckBu\WG\|dYLl[EBi\nSncjCzNEB1dyB2NTDtbY5{NCCHQ{WwJF0hOC5yNUOg{txONg>?	Ml35QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ4OUiwPFQoRjJ{Nkm4NFg1RC:jPh?=
TF1	M4ez[mZ2dmO2aX;uJIF{e2G7		MVKyNEBucW6\|	NXjndXMzUW6qaXLpeIlwdiCxZjDKRWsyKGmwIHj1cYFvKFSIMTDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKEmONj3pcoR2[2WmIGPURXQ{KHCqb4PwbI9zgWyjdHnvckBqdmO3YnH0[YQh\m:{IEKwJI1qdnNiZn;scI94\WRiYomgTWw3KGOqYXzs[Y5o\SCob4KgN\|AhdWmwczygSWM2OCB;IECuNFU{KM7:TT6=	MU[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzZ3OUKxOEc,OjN4NUmyNVQ9N2F-
Ba/F3	MVrGeY5kfGmxbjDhd5NigQ>?		MY[2NEBucW6\|	M1X4TmlvcGmkaYTpc44hd2ZiVFXMMYZ2e2WmIFrBT\|Mh\XiycnXzd4VlKGmwIFLhM2Y{KGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gV3RCXDVicHjvd5Bpd3K7bHH0bY9vKGGodHXyJFYxKG2rboOgZpkhSWyyaHHTZ5Jm\W5iYYPzZZktKEmFNUCgQUAxNjB3NDFOwG0v	M4P3ZVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MEi3O\|UxLz5{MkC4O\|c2ODxxYU6=
T-cells	MULGeY5kfGmxbjDhd5NigQ>?			MmOyTY5pcWKrdHnvckBw\iCjbHzv[4VvcWNiY3XscJMue3SrbYXsZZRm\CCycn;sbYZmemG2aX;uJIlvKG2xbnvlfUBVKGOnbHzzJIJ6KG2reHXkJIx6dXCqb3P5eIUhemWjY4Tpc44hdWW2aH;kMEBKSzVyIE2gNE4xPTdizszNMi=>	MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPDV7M{G4Nkc,OTR3OUOxPFI9N2F-
CD34+	NGK0UZlHfW6ldHnvckBie3OjeR?=			NXjz[FF3UW6qaXLpeIlwdiCxZjDKRWszKGmwIHj1cYFvKEOGM{SrJINmdGy\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiRWDPMY1m\GmjdHXkJINmdGxicILvcIln\XKjdHnvckwhUUN3MDC9JFAvODdzIN88UU4>	M2nYXlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4OUK3OFI{Lz5{NkmyO\|QzOzxxYU6=
TF1	M2\YUmZ2dmO2aX;uJIF{e2G7			Mo\XTY5pcWKrdHnvckBw\iCLTEStbY5lfWOnZDDwdo9tcW[ncnH0bY9vKG:oIGTGNUBk\WyuczygTWM2OCB;IECuNFgh\|ryPLh?=	M4WwPVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF4OUO0OFU4Lz5zNkmzOFQ2PzxxYU6=
T-cells	NXT3eHFxTnWwY4Tpc44h[XO\|YYm=			NXfUe5NCUW6qaXLpeIlwdiCxZjDhcIxw\2WwaXOgZ4VtdHNvc4TpcZVt[XSnZDDwdo9tcW[ncnH0bY9vKGmwIHj1cYFvKFRiY3XscJMh[nlibXn4[YQhdHmvcHjvZ5l1\SC{ZXHjeIlwdiCvZYToc4QtKEmFNUCgQUAxNjB6NzFOwG0v	MkXOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTR3OUOxPFIoRjF2NUmzNVgzRC:jPh?=
TF1	MUTGeY5kfGmxbjDhd5NigQ>?		M4fEUFIxKG2rboO=	MUDJcohq[mm2aX;uJI9nKEqDS{KgbY4hcHWvYX6gWGYyKGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gSXBQNWmwZIXj[YQhW1SDVEWgdIhwe3Cqb4L5cIF1cW:wIHnuZ5Vj[XSnZDDmc5IhOjBibXnud{BxemmxcjD0c{BGWE9vaX7keYN1cW:wIH3lZZN2emWmIHHmeIVzKDNyIITvJFQ2KG2rboOsJGVEPTBiPTCwMlA6OyEQvF2u	MnrzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ4OUiwPFQoRjJ{Nkm4NFg1RC:jPh?=
TF1	MWnGeY5kfGmxbjDhd5NigQ>?		NF\ScW0zOCCvaX7z	NVLMbI81UW6qaXLpeIlwdiCxZjDKRWszKGmwIHj1cYFvKFSIMTDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKEWSTz3pcoR2[2WmIGPURXQ2KHCqb4PwbI9zgWyjdHnvckBqdmO3YnH0[YQh\m:{IEKwJI1qdnNiZn;scI94\WRiYomgTWw3KGOqYXzs[Y5o\SCob4KgN\|AhdWmwczygSWM2OCB;IECuNFk{KM7:TT6=	NYT6RYl2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO2OVkzOTRpPkKzOlU6OjF2PD;hQi=>
PBMC	MX3GeY5kfGmxbjDhd5NigQ>?			MmrVTY5pcWKrdHnvckBw\iCMQVuxJIlvKGi3bXHuJHBDVUNiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBKVC14LXnu[JVk\WRiTVPQNUB{\WO{ZYTpc44tKEmFNUCgQUAxNjB7NTFOwG0v	NGS1T4E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkmyO\|QzOyd-Mk[5Nlc1OjN:L3G+
TF1	NGjCPWdHfW6ldHnvckBie3OjeR?=		Mn3YNkBpenN?	NWDFV4tvUW6qaXLpeIlwdiCxZjDKRWszKGmwIFfNR3NHNXO2aX31cIF1\WRiaIXtZY4hXEZzIHPlcIx{KGG\|c3Xzd4VlKGG\|IIP1dJBz\XO\|aX;uJI9nKFOWQWS1JJBpd3OyaH;yfYxifGmxbjDwdoVqdmO3YnH0[YQh\m:{IEKgbJJ{KG[xbHzve4VlKGK7IFfNR3NHKHO2aX31cIF1cW:wIH\vdkA2OCCvaX7zJIJ6KE[DQ2OgdoVi\GW{IHHuZYx6e2m\|LDDJR\|UxKD1iMD6wPVUh\|ryPLh?=	NF[2dJg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{GzNFM2QSd-MkexN\|A{PTl:L3G+
TF1	NWHNbGtSTnWwY4Tpc44h[XO\|YYm=			MWrJcohq[mm2aX;uJI9nKEqDS{KgbY4hTVCRLYP0bY12dGG2ZXSgbJVu[W5iVF[xJINmdGy\|IHX4dJJme3Orbnegd5Ri[my7IHnueIVoemG2ZXSgZoV1[S2uYXP0ZY1ie2VicnXwc5J1\XJiZ3Xu[UB2dmSncjDjc451em:uIH;mJHNVSVR3IILld5BwdnOnIHXs[Y1mdnS\|IHnuJIlvfGW{ZnXyc44hemWpdXzheI9zgSCoYXP0c5IhOSCpZX7lJJBzd22xdHXyJIJ6KG[udX;y[ZNk\W6lZTDhd5NigSxiSVO1NEA:KDBwMUC3JO69VS5?	NHXnVlc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUG1OlE{Pid-MkmxOVYyOzZ:L3G+
Sf9	MXfGeY5kfGmxbjDhd5NigQ>?			NWfT[llxUW6qaXLpeIlwdiCxZjDHV3QufGGpZ3XkJIh2dWGwIFrBT\|Eh[2G2YXz5eIlkKGSxbXHpckBmgHC{ZYPz[YQhcW5iU3[5JINmdGy\|IHL5JGVNUVODLDDJR\|UxKD1iMD6xNUDPxE1w	MWK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTFyNUexNUc,OjFzMEW3NVE9N2F-
T-cells	MWPGeY5kfGmxbjDhd5NigQ>?			MV;Jcohq[mm2aX;uJI9nKGGubH;n[Y5q[yClZXzsd{1{fGmvdXzheIVlKHC{b3zp[oVz[XSrb36gbY4hdW:3c3WgWEBk\WyuczDifUBucXinZDDsfY1xcG:leYTlJJJm[WO2aX;uJI1mfGixZDygTWM2OCB;IECuNVE2KM7:TT6=	M4nrW\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF2NUmzNVgzLz5zNEW5N\|E5OjxxYU6=
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CTLL-2	M175d2FvfGmycn;sbYZmemG2aY\lJIF{e2G7		M3vMWVczKGi{cx?=	M1zC[GFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgTWwuOi2\|dHnteYxifGWmIH3veZNmKEOWTFytNkBk\WyuczDlfJBz\XO\|aX7nJGpCUzFxSlHLN{Bi\nSncjC3NkBpenNiYomgZYxidWG{IHLseYUh[XO\|YYmsJGlEPTBiPTCwMlE{OiEQvF2u	NWLDUoRSRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUm3OlIzOzhpPkG5O\|YzOjN6PD;hQi=>
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T-cells	NE\uOY9HfW6ldHnvckBie3OjeR?=			M{fybmlvcGmkaYTpc44hd2ZiSlHLNk8yKGmwIHj1cYFvKFRiY3XscJMh\XiycnXzd4lv\yCFREOgZZN{\XO\|ZXSgZZMhcW6qaXLpeIlwdiCxZjDJSm5o[W2vYT3zeIlufWyjdHXkJHNVSVRzIIDoc5NxcG:{eXzheIlwdixiSVO1NEA:KDBwMUeg{txONg>?	NXjVdmk3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO1OFA3PDhpPkKzOVQxPjR6PD;hQi=>
insect	MW\GeY5kfGmxbjDhd5NigQ>?			MWjJcohq[mm2aX;uJI9nKEeVVD30ZYdo\WRiVInrNkBmgHC{ZYPz[YQhcW5iaX7z[YN1KGOnbHzzJJV{cW6pIEO1JJVOKEGWUDygTWM2OCB;IECuNVc3KM7:TT6=	M3\NfVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUW1OlA2Lz5{MUG1OVYxPTxxYU6=
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TF1	NUnuW4QyTnWwY4Tpc44h[XO\|YYm=			NUfTZlhTUW6qaXLpeIlwdiCxZjDKRWszKGmwIHj1cYFvKFSIMTDj[YxteyCjc4Pld5Nm\CCjczDzeZBxemW\|c3nvckBw\iClZXzsJIdzd3e2aDygTWM2OCB;IECuNlc2OSEQvF2u	M4SwWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5N{exNVgxLz5{N{e3NVE5ODxxYU6=
CD34+	NXHzfYhxTnWwY4Tpc44h[XO\|YYm=			NUTGNmhKUW6qaXLpeIlwdiCxZjDKRWszKGixbX;kbY1meiCrbjDoeY1idiCFREO0L{Bk\WyuczDzdIls\WRiaX70c{BpfW2jbjD3bI9t\SCkbH;v[EBie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGVRVy2rbnT1Z4VlKFOWQWStOUBxcG:\|cHjvdplt[XSrb36gdJJmcW6ldXLheIVlKG[xcjC0OUBucW6\|IH\vcIxwf2WmIHL5JGVRVyCjZHTpeIlwdiCvZXHzeZJm\CCjZoTldkAyPSCvaX7zJIJ6KE[DQ2OgZY5idHm\|aYOsJGlEPTBiPTCwMlMxOiEQvF2u	MoSzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR2MUe1N\|MoRjJ2NEG3OVM{RC:jPh?=
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T-cells	MXLGeY5kfGmxbjDhd5NigQ>?		M4L4Z\|Mh\GG7cx?=	NHXwRnhKdmirYnn0bY9vKG:oIHPlcIwheHKxbHnm[ZJifGmxbjDv[kBKVDJvYXP0bZZifGWmIHHu[EBETDNiYX7kJGNFOjhiYX70bYJw\Hlvc4TpcZVt[XSnZDDtc5V{\SCFREStdI9{cXSrdnWgWEBk\WyuczDh[pRmeiB\|IHThfZMh[nliWGTUJIF{e2G7LDDJR\|UxKD1iMD62N{DPxE1w	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODR4MEi0Nkc,OzB2NkC4OFI9N2F-
NK92	M{HiSmZ2dmO2aX;uJIF{e2G7		MnXGNlAhdWmwcx?=	M2rDVGlvcGmkaYTpc44hd2ZiVGnLNkBqdiCqdX3hckBPUzl{IHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhUUxzMj3pcoR2[2WmIGPURXQ1KHCqb4PwbI9zgWyjdHnvckBqdmO3YnH0[YQh\m:{IEKwJI1qdnNiZn;scI94\WRiYomgTWwyOiClaHHscIVv\2ViZn;yJFQ2KG2rboOsJGVEPTBiPTCwMlcyKM7:TT6=	M3ftelxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NkW5NlE1Lz5{M{[1PVIyPDxxYU6=
TF1	Mm\ZSpVv[3Srb36gZZN{[Xl?			M37xN2lvcGmkaYTpc44hd2ZiSVyzMYlv\HWlZXSgdJJwdGmoZYLheIlwdiCxZjDUSlEh[2WubIOsJGlEPTBiPTCwMlgh\|ryPLh?=	NV;CS5BvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMU[5N\|Q1PTdpPkG2PVM1PDV5PD;hQi=>
UT7	NEez[nZHfW6ldHnvckBie3OjeR?=			MWDJcohq[mm2aX;uJI9nKEqDS{KgbY4hcHWvYX6gWXQ4KGOnbHzzJIF{e2W\|c3XkJIF{KHO3cIDy[ZN{cW:wIH;mJGVRVy2\|dHnteYxifGWmIGPURXQ2KHCqb4PwbI9zgWyjdHnvckBjgSCDbIDoZXNkemWnbjDhd5NigSxiSV7IJF0hOS5zMjFOwG0v	NXLx[491RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[zO\|I3PTNpPkK2N\|czPjV\|PD;hQi=>
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T-cells	NHPXVpVHfW6ldHnvckBie3OjeR?=		MWq3NkBpenN?	NYPIR\|FlUW6qaXLpeIlwdiCxZjDKRWs{KGmwIILheEB{eGynbn;jfZRq[yCWIHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDpckBKVC1{LXnu[JVk\WRiY3XscEBxem:uaX\ldoF1cW:wIHHmeIVzKDd{IHjyd{BjgSCPVGOgZZN{[XluIFnDOVAhRSBzLkKg{txONg>?	M2qwVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyMUO5OVc2Lz5\|MEGzPVU4PTxxYU6=
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BAF3	M4ftWGFvfGmycn;sbYZmemG2aY\lJIF{e2G7		NWfkXnpjPzJiaILz	MoCwRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDtc5V{\SCEQV[zJINmdGy\|IHX4dJJme3OrbnegWGVNNUqDS{Kgb4lv[XOnIHHmeIVzKDd{IHjyd{BjgSCjbHHtZZIh[my3ZTDhd5NigSxiSVO1NEA:KDFwNUe0JO69VS5?	NFrk[II9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUe2NlI{QCd-MUm3OlIzOzh:L3G+
HEL	NYPCRlJtTnWwY4Tpc44h[XO\|YYm=		MoWwNUBpeg>?	NV\UdllzUW6qaXLpeIlwdiCxZjDKRWszKFZ4MUfGJI12fGGwdDDpckBpfW2jbjDISWwh[2WubIOgZYZ1\XJiMTDodkwhUUN3MDC9JFQvPzJ2IN88UU4>	M3fvTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5N{exNVgxLz5{N{e3NVE5ODxxYU6=
Jurkat	MkLjSpVv[3Srb36gZZN{[Xl?		NF;jVJUzPCCqcoO=	MnLSTY5pcWKrdHnvckBw\iCjboTpMWNFOy:jboTpMWNFOjhvaX7keYNm\CCLTEKgdJJw\HWldHnvckBqdiCqdX3hckBLfXKtYYSgZ4VtdHNiYX\0[ZIhOjRiaILzJIJ6KHOlaX70bYxt[XSrb36gZ492dnSrbnesJGlEPTBiPTC3Mlg1KM7:TT6=	NXS3SW5XRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUS1PVMyQDJpPkG0OVk{OTh{PD;hQi=>
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YT	M3rLdmZ2dmO2aX;uJIF{e2G7	NWHjbHA4OzBibnevcYw>		MW\Jcohq[mm2aX;uJI9nKEmOMj3pcoR2[2WmIGPURXQ2SSCyaH;zdIhwenmuYYTpc44hcW5iaIXtZY4hYVRiY3XscJMh[XRiM{CgcocwdWxiYomgbY1ufW6xYnzveJRqdmdiYX7hcJl{cXN?	M3P3ZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF2NUmzNVgzLz5zNEW5N\|E5OjxxYU6=
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NK-cells	M3rVUGludXWwb4P1dJBz\XO\|aY\lJIF{e2G7	NYjKSXVjOSC2bzC1JI1oN2up	MXq0JJdm\Wu\|	NIraUJFKdW23bn;zeZBxemW\|c3n2[UBi[3Srdnn0fUBqdiCwYXn2[UBkgW6xbX;s[5V{KG2xbnvlfUBie3Onc4Pl[EBieyCnZn\lZ5Qhd25iQ1SzMWNFOTZtIF7LJINmdGy\|IHH0JFEhfG9iNTDt[{9s\yxicH:g[o9zKDRid3Xlb5M>	NVXC[mpVRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUS1PVMyQDJpPkG0OVk{OTh{PD;hQi=>
T-cells	NUfMW4lCTnWwY4Tpc44h[XO\|YYm=	NXnkZYFwPSC2bzC1NFAhdk1?	NIXGTWIyKGi{	MVXJcohq[mm2aX;uJI9nKEmOMj3pcoR2[2WmIGP0ZZQ2KHCqb4PwbI9zgWyjdHnvckBqdiCqdX3hckBETDRtIGSgZ4VtdHNiYYSgOUB1dyB3MECgcm0h[W[2ZYKgNUBpeiCkeTDX[ZN1\XKwIHLsc5Q>	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTB3M{e1Okc,OTlyNUO3OVY9N2F-
SUM149PT	MVLGeY5kfGmxbjDhd5NigQ>?	NEjpXHI{KHWP	MVexOkBpenN?	MXzJcoR2[3Srb36gc4YhWFSSTk[gbY4hcHWvYX6gV3VOOTR7UGSgZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iCVVFHUN{BxcG:\|cHjvdplt[XSrb36gZZQhOyC3TTDh[pRmeiBzNjDodpMh[nliV3XzeIVzdiCkbH;0eIlv\yCjbnHsfZNqeyCrbjDwdoV{\W6lZTDv[kBx\XK4YX7h[IF1\Q>?	M1fUPFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUe4NVEzLz5{NEm3PFEyOjxxYU6=
Hs578T	Ml;hSpVv[3Srb36gZZN{[Xl?	M2PEVVMhfU1?	MU[xOkBpenN?	NHu4UY1KdmS3Y4Tpc44hd2ZiUGTQUlYhcW5iaIXtZY4hUHN3N{jUJINmdGy\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiU2TBWFMheGixc4Doc5J6dGG2aX;uJIF1KDNidV2gZYZ1\XJiMU[gbJJ{KGK7IGfld5Rmem5iYnzveJRqdmdiYX7hcJl{cXNiaX6gdJJme2WwY3Wgc4YheGW{dnHuZYRifGV?	MkfpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7N{ixNVIoRjJ2OUe4NVEzRC:jPh?=
T-cells	NUD0fZVRTnWwY4Tpc44h[XO\|YYm=	NWjzT\|I4PTBidH:gN\|AxKG6P	MnLVNUBpeg>?	NWGwUZhwUW6qaXLpeIlwdiCxZjDKRWsyN0qDS{OgbY4hcHWvYX6gR2Q1KHCxc3n0bZZmKFRiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBKVDRvc4TpcZVt[XSnZDDTWGFVPiCyaH;zdIhwenmuYYTpc44h[XRiNUCgeI8hOzByIH7NJJBz\WmwY4XiZZRm\CCob4KgNUBpeiCob3zsc5dm\CCkeTDJUE01KHO2aX31cIF1cW:wIH3lZZN2emWmIHHmeIVzKDNyIH3pcpMh[nliaX3teY5w[myxdDDhcoFtgXOrcx?=	M1XudlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7OEWyNFY5Lz5{OUi1NlA3QDxxYU6=
T-cells	M2C1T2Z2dmO2aX;uJIF{e2G7	NVi1XIpvPTBidH:gN\|AxKG6P	M4XwelEhcHJ?	MlvoTY5pcWKrdHnvckBw\iCMQVuxM2pCUzNiaX6gbJVu[W5iQ1S0JJBwe2m2aY\lJHQh[2WubIOgZZN{\XO\|ZXSgZZMhcW6qaXLpeIlwdiCxZjDJUFIue3SrbYXsZZRm\CCVVFHUOUBxcG:\|cHjvdplt[XSrb36gZZQhXHm{LU[5OUBz\XOrZIXlJIF1KDVyIITvJFMxOCCwTTDwdoVqdmO3YnH0[YQh\m:{IEGgbJIh\m:ubH;3[YQh[nliSVytNkB{fGmvdXzheIlwdiCvZXHzeZJm\CCjZoTldkA{OCCvaX7zJIJ6KGmvbYXuc4Jtd3RiYX7hcJl{cXN?	Mn;XQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl6NUKwOlgoRjJ7OEWyNFY5RC:jPh?=
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TALL-1	M3fhVWZ2dmO2aX;uJIF{e2G7	MkTZNUB2VQ>?	NI\kcmM{KGi{cx?=	NUXDfoc4UW6qaXLpeIlwdiCxZjDKRWs{KGmwIHj1cYFvKFSDTFytNUBk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIFnMMVIhcW6mdXPl[EBUXEGWNTDwbI9{eGixconsZZRqd25iYYSgNUB2VSCycnXpcoN2[mG2ZXSg[o9zKDNiaILzJIZwdGyxd3XkJIJ6KEmOLUKgbY5lfWO2aX;uJI1m[XO3cnXkJIFnfGW{IEOwJI1qdnNiYomgbY1ufW6xYnzveJRqdmd?	M1HLTFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MkW4OVIyLz5{NkK1PFUzOTxxYU6=
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Huh7	M1v1VGZ2dmO2aX;uJIF{e2G7	NEjQUmcyOCC3TR?=	NEHRPWo{OCCvaX7z	MYTJcohq[mm2aX;uJI9nKFS7a{KgbY4hcHWvYX6gTJVpPyClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25ib3[gTWZP[WyyaHG1MYlv\HWlZXSgV3RCXDNicHjvd5Bpd3K7bHH0bY9vKGG2IEGwJJVOKHC{ZT3pcoN2[mG2ZXSg[o9zKDNyIH3pcpMh[mWob4LlJGlHVmGucHjhOUB{fGmvdXzheIlwdiCob4KgN\|AhdWmwczDtbY5{KGK7IHntcZVvd2Kub4T0bY5o	MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjJ\|MUG1PUc,OjZ{M{GxOVk9N2F-
Huh7	MmLHSpVv[3Srb36gZZN{[Xl?	NYWycY1ZOTBidV2=	M1PDflMxKG2rboO=	M2XDWWlvcGmkaYTpc44hd2ZiVInrNkBqdiCqdX3hckBJfWh5IHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDv[kBj[XOjbDDs[ZZmdCCVVFHUN{BxcG:\|cHjvdplt[XSrb36gZZQhOTBidV2gZYZ1\XJiM{CgcYlveyCkeTDpcY12dm:kbH;0eIlv\w>?	MnLPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ{M{GxOVkoRjJ4MkOxNVU6RC:jPh?=
Huh7	M2j2TGZ2dmO2aX;uJIF{e2G7	NY\MNWRxOSC3TR?=	MX[zNEBucW6\|	MUPJcohq[mm2aX;uJI9nKFS7a{KgbY4hcHWvYX6gTJVpPyClZXzsd{Bie3Onc4Pl[EBieyC{ZXT1Z5Rqd25ib3[gTWZP[WyyaHG1MYlv\HWlZXSgV3RCXDNicHjvd5Bpd3K7bHH0bY9vKGG2IEGgeW0heHKnLXnuZ5Vj[XSnZDDmc5IhOzBibXnud{Bj\W[xcnWgTWZP[WyyaHG1JJN1cW23bHH0bY9vKG[xcjCzNEBucW6\|IH3pcpMh[nliaX3teY5w[myxdITpcoc>	MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjJ\|MUG1PUc,OjZ{M{GxOVk9N2F-

Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID

Western blot	JAK3 / STAT5 / p-STAT5 ; LMP1 / EBNA1 / BZLF1 ; JAK3 / p-JAK3 / STAT3	27732937 26082451
Growth inhibition assay	Cell number	27732937

In vivo

In a murine model of heterotopic heart transplantation (DBA2 donor heart into C57/BL6 host), CP-690550 results in a dose-dependent increase in survival of transplanted hearts.The EC50 (drug concentration in blood at which 50% of mice will maintain their graft for >28 days) to be ~60 ng/mL.CP-690550 prevents rejection of allogeneic kidneys in nonhuman primate (NHPs, macaca fascicularis) (MST of 62 and 83 days for the 50 to 100 ng/ml groups and 200 to 400 ng/ml groups, respectively). ^[1] Mice chronically dosed with CP-690550 (1.5-15 mg/kg/day) demonstrates dose and time-dependent alterations in lymphocyte subsets when examined by flow cytometry. The most dramatic change observed is a 96% reduction in splenic NK1.1+TCRb-cell numbers following 21 days of treatment. Delayed-type hypersensitivity (DTH) responses in sensitized mice are reduced in a dose-dependent manner following treatment with CP-690550 (1.87–30 mg/kg, s.c.). Extended survival of neonatal Balb/c hearts implanted into the ear pinna of MHC mismatched C3H/HEN mice is observed with CP-690550 monotherapy (10–30 mg/kg/day), but improved upon combination with cyclosporin (10 mg/kg/day). ^[2]

Protocol (from reference)

Kinase Assay: ^[1]	JAK3 Kinase Assay: A fragment encoding the catalytic domain of human JAK3 (785aa to 1125aa, JH1 catalytic domain) is amplified by PCR from the full length cDNA and cloned into the EcoRI site of the baculovirus transfer vector pVL1393. Recombinant baculovirus is used to infect Sf9 (Spodoptera frugipedra) cells and recombinant GSTJAK3 fusion protein is isolated on glutathione sepharose. The fusion protein is eluted with reduced glutathione and stored in buffer containing 50 mM Tris, pH 7.5, 10 mM DTT and 10% glycerol. JAK3 kinase activity is measured by ELISA as follows: Plates are coated overnight with a random L-glutamic acid and tyrosine co-polymer (4:1) (100 ug/mL). The plates are washed and recombinant JAK3 JH1:GST (100 ng/well) with or without inhibitors is incubated at room temperature for 30 minutes, after which HRP-conjugated PY20 anti-phosphotyrosine antibody (ICN) is added and developed by TMB (3,3',5,5'-tetramethylbenzidine). Other kinases (Table 1) are produced in E. coli or in insect cells, depending upon what is found to be optimal for the given kinase. The catalytic activity of tyrosine kinases is easured using the aftorementioned ELISA, whereas serine/threonine kinases are assayed using radioactive enzyme assays.
Cell Research: ^[1]	Cell lines: Human T blasts cell Concentrations: 0-4000 nM Incubation Time: 4 days Method: To measure IL-2-dependent proliferation, isolated lymphocytes are resuspended to a cell density of 1-2 × 10⁶/mL in complete RPMI medium (RPMI 1640 containing 10% (w/v) fetal calf serum (FCS), 1%(w/v) penicillin and treptomycin).Phytohemagluttinin (PHA) is added to a final concentration of 10mg/mL, and the culture incubated for 3 days at 37 °C in a humidified 5% (v/v) CO₂ incubator to upregulate IL-2R and JAK3 expression. IL-2 (200U/mL), with or without CP-690,550 is then added and the cells are incubated for 72 hours at 37 °C in a humidified 5% (v/v) CO₂ incubator, after which 50 mL of ³H-thymidine (5mCi/mL) is added. The plates are incubated for an additional 18 hours, harvested with a 96-well harvester, and counted on a scintillation counter. HUO3 cells are maintained in culture with granulocyte-macrophage colony stimulating factor and human foreskin fibroblasts are maintained in culture with 10% fetal calf serum. CP-690550 is added to freshly plated cells and cultured for 4 days. 3Hthymidine is added during the last 18 hours of the culture period.
Animal Research: ^[1]	Animal Models: DBA/2 and C57/BL6 mice Dosages: 0-136 ng/mL Administration: Administered via osmotic minipump infusion

References

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Solubility (25°C)

In vitro


In vivo	Add solvents to the product individually and in order (Data is from Selleck tests instead of citations): 2% DMSO+30% PEG 300+ddH2O For best results, use promptly after mixing. Click to purchase: PEG300	5mg/mL

Chemical Information

Molecular Weight	312.37
Formula	C₁₆H₂₀N₆O
CAS No.	477600-75-2
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	CC1CCN(CC1N(C)C2=NC=NC3=C2C=CN3)C(=O)CC#N

Download Tofacitinib (CP-690550) SDF

In vivo Formulation Calculator (Clear solution)

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Clinical Trial Information

NCT Number	Recruitment	Interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05082428	Not yet recruiting	--	Ulcerative Colitis	Pfizer	December 1 2021	--
NCT05087589	Recruiting	Drug: Tofacitinib	Primary Sjögren''s Syndrome	Peking University People''s Hospital	November 18 2021	Phase 2
NCT04768504	Recruiting	Drug: Tofacitinib 10 mg	Immune-Mediated Colitis	Khashayar Esfahani\|Sir Mortimer B. Davis - Jewish General Hospital	November 15 2021	Phase 2
NCT04624230	Recruiting	Drug: tofacitinib	Ulcerative Colitis	Pfizer	August 12 2021	Phase 3
NCT04496960	Recruiting	Drug: tofacitinib\|Other: Placebo	Sjogren''s Syndrome	National Institute of Dental and Craniofacial Research (NIDCR)\|National Institutes of Health Clinical Center (CC)	May 18 2021	Phase 1\|Phase 2
NCT04424303	Recruiting	Drug: Tofacitinib	Ulcerative Colitis	Pfizer	December 7 2020	--

(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

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Frequently Asked Questions

Question 1:
I was just wondering what the main differences between S2789 and S5001?

Answer:
S2789(Tofacitinib (CP-690550)) is the base form of S5001 (Tofacitinib (CP-690550) Citrate). The biological activity of these two compounds are same. The S5001 (Tofacitinib (CP-690550) Citrate) is more suitable for oral administration.

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