Tofacitinib (CP-690550)

Name: Tofacitinib (CP-690550)
Brand: Selleck Chemicals
SKU: S2789
Rating: 5 (106 reviews)

For research use only.

Licensed by Pfizer Catalog No.S2789 Synonyms: Tasocitinib

106 publications

Tofacitinib (CP-690550) Chemical Structure

CAS No. 477600-75-2

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.

Selleck's Tofacitinib (CP-690550) has been cited by 106 publications

Nat Med, 2017, 23(3):291-300

PubMed: 28191885 ( click the link to review the publication )

Nat Methods, 2016, 13(2):151-7

PubMed: 26689262 ( click the link to review the publication )

Arthritis Rheumatol, 2021, 10.1002/art.41666

PubMed: 33512089 ( click the link to review the publication )

Anal Chem, 2021, 10.1021/acs.analchem.0c03956

PubMed: 33470103 ( click the link to review the publication )

Hum Mol Genet, 2021, ddab035

PubMed: 33517393 ( click the link to review the publication )

Hepatology, 2020, 25

PubMed: 32333814 ( click the link to review the publication )

Leukemia, 2020, 10.1038/s41375-020-01077-1

PubMed: 33149267 ( click the link to review the publication )

Cancers (Basel), 2020, 12(6):E1603

PubMed: 32560455 ( click the link to review the publication )

PLoS Pathog, 2020, 16;16(3):e1008341

PubMed: 32176725 ( click the link to review the publication )

Cancer Discov, 2020, 10(4):608-625

PubMed: 32046984 ( click the link to review the publication )

J Eur Acad Dermatol Venereol, 2020, 34(4):800-809

PubMed: 31793105 ( click the link to review the publication )

Mol Cell Proteomics, 2020, 10.1074/mcp.RA119.001504

PubMed: 32102969 ( click the link to review the publication )

J Neuroinflammation, 2020, 29;17(1):170

PubMed: 32471455 ( click the link to review the publication )

Carcinogenesis, 2020, 41(7):993-1004

PubMed: 31740922 ( click the link to review the publication )

J Virol, 2020, JVI.01413-20

PubMed: 33177205 ( click the link to review the publication )

Exp Eye Res, 2020, S0014-4835(20)30611-4

PubMed: 33171193 ( click the link to review the publication )

Mol Biol Rep, 2020, 10

PubMed: 32277445 ( click the link to review the publication )

J Clin Med, 2020, 9(3)

PubMed: 32214018 ( click the link to review the publication )

ACR Open Rheumatol, 2020, 2(1):3-10

PubMed: 31943973 ( click the link to review the publication )

Clin Exp Immunol, 2020, 201(3):233-243

PubMed: 32538493 ( click the link to review the publication )

Cells, 2020, 9(7):1694

PubMed: 32679790 ( click the link to review the publication )

JCI Insight, 2020, 5(4)

PubMed: 32102981 ( click the link to review the publication )

Cells, 2020, 9(9):E1927

PubMed: 32825270 ( click the link to review the publication )

Onco Targets Ther, 2020, 13:7165-7176

PubMed: 32801748 ( click the link to review the publication )
Nat Commun, 2019, 10(1):4353

PubMed: 31554795 ( click the link to review the publication )

J Thromb Haemost, 2019, 10.1111/jth.14525

PubMed: 31145836 ( click the link to review the publication )

Pharmacol Res, 2019, 143:73-85

PubMed: 30862605 ( click the link to review the publication )

Arthritis Res Ther, 2019, 21(1):284

PubMed: 31831067 ( click the link to review the publication )

Phytomedicine, 2019, 59:152755

PubMed: 31005814 ( click the link to review the publication )

J Orthop Res, 2019, 37(4):972-980

PubMed: 30816586 ( click the link to review the publication )

J Cancer Res Clin Oncol, 2019, 145(2):411-427

PubMed: 30483898 ( click the link to review the publication )

Oncol Rep, 2019,

PubMed: 31173242 ( click the link to review the publication )

Immunotherapy, 2019, 11(6):483-496

PubMed: 30860437 ( click the link to review the publication )

Sci Immunol, 2019, 4(40)

PubMed: 31653719 ( click the link to review the publication )

J Clin Invest, 2018, 128(1):387-401

PubMed: 29200404 ( click the link to review the publication )

Sci Signal, 2018,

PubMed: 29511118 ( click the link to review the publication )

Allergy, 2018, 73(9):1881-1891

PubMed: 29528494 ( click the link to review the publication )

J Cell Sci, 2018, 131(10)

PubMed: 29678906 ( click the link to review the publication )

J Transl Med, 2018, 16(1):156

PubMed: 29879987 ( click the link to review the publication )

Ann Surg Oncol, 2018, 25(8):2449-2456

PubMed: 29948421 ( click the link to review the publication )

Clin Exp Rheumatol, 2018, 36(4):559-567

PubMed: 29352846 ( click the link to review the publication )

SLAS Discov, 2018, 23(8):777-789

PubMed: 29447055 ( click the link to review the publication )

Anticancer Res, 2018, 38(4):1967-1977

PubMed: 29599312 ( click the link to review the publication )

Hepatology, 2018, 67(4):1237-1252

PubMed: 29059468 ( click the link to review the publication )

Immunity, 2017, 21;46(2):220-232

PubMed: 28228280 ( click the link to review the publication )

Nat Chem Biol, 2017, 13(1):38-45

PubMed: 27820799 ( click the link to review the publication )

Nat Commun, 2017, 1;8(1):1232

PubMed: 29089541 ( click the link to review the publication )

PLoS Pathog, 2017, 13(12):e1006740

PubMed: 29267399 ( click the link to review the publication )
Arch Toxicol, 2017, 91(10):3385-3402

PubMed: 28365849 ( click the link to review the publication )

Arch Toxicol, 2017, 91(8):2921-2938

PubMed: 28032146 ( click the link to review the publication )

J Immunol, 2017,

PubMed: 28039301 ( click the link to review the publication )

J Virol, 2017, 91(9)

PubMed: 28202754 ( click the link to review the publication )

Sci Rep, 2017, 7(1):6779

PubMed: 28754958 ( click the link to review the publication )

Sci Rep, 2017, 7(1):10965

PubMed: 28887478 ( click the link to review the publication )

Sci Rep, 2017, 7:43441

PubMed: 28240310 ( click the link to review the publication )

Am J Pathol, 2017, 187(5):980-986

PubMed: 28284718 ( click the link to review the publication )

Inflamm Res, 2017, 66(1):25-37

PubMed: 27628164 ( click the link to review the publication )

Biochem Biophys Res Commun, 2017, 490(2):194-201

PubMed: 28601639 ( click the link to review the publication )

Oncol Lett, 2017,

PubMed: 28928840 ( click the link to review the publication )

JCI Insight, 2017,

PubMed: 29093269 ( click the link to review the publication )

Proc Natl Acad Sci U S A, 2017, 114(6):E980-E989

PubMed: 28049849 ( click the link to review the publication )

Blood, 2016, 127(10):1287-96

PubMed: 26738536 ( click the link to review the publication )

Ann Rheum Dis, 2016, 75(1):311-5

PubMed: 26353790 ( click the link to review the publication )

Nat Chem Biol, 2016, 12(5):373-9

PubMed: 27018889 ( click the link to review the publication )

Leukemia, 2016, 30(6):1311-9

PubMed: 26854024 ( click the link to review the publication )

Sci Signal, 2016, 9(456):ra116

PubMed: 27899526 ( click the link to review the publication )

Oncoimmunology, 2016, 5(3):e1094598

PubMed: 27141355 ( click the link to review the publication )

Transplant Proc, 2016, 48(9):3046-3052

PubMed: 27932144 ( click the link to review the publication )

Clin Cancer Drugs, 2016, 3(2):131-137

PubMed: 29046866 ( click the link to review the publication )

J Immunol Res, 2016, 2016:5021537

PubMed: 28070525 ( click the link to review the publication )

Blood, 2015, 126(6):766-78.

PubMed: 26041742 ( click the link to review the publication )

Blood, 2015, 126(4):508-19

PubMed: 26082451 ( click the link to review the publication )
Mol Syst Biol, 2015, 11(3):797

PubMed: 25814555 ( click the link to review the publication )

J Med Chem, 2015, 58(16):6589-606

PubMed: 26258521 ( click the link to review the publication )

J Immunol, 2015, 10.4049/jimmunol.1402739

PubMed: 25732730 ( click the link to review the publication )

Prostate, 2015, 10.1002/pros.22945

PubMed: 25560638 ( click the link to review the publication )

J Biol Chem, 2015, 290(48):29022-34

PubMed: 26446793 ( click the link to review the publication )

J Biol Chem, 2015, 290(34):20972-83

PubMed: 26152718 ( click the link to review the publication )

Blood, 2014, 124(5):761-70

PubMed: 24957145 ( click the link to review the publication )

Arthritis Rheumatol , 2014, 66(1):121-9

PubMed: 24431283 ( click the link to review the publication )

Arthritis Rheumatol , 2014, 10.1002/art.39007

PubMed: 25545152 ( click the link to review the publication )

Front Cell Neurosci, 2014, 8:183

PubMed: 25071444 ( click the link to review the publication )

Front in Cell Neurosci, 2014, 0.460416666666667

PubMed: ( click the link to review the publication )

Antimicrob Agents Chemother, 2014, 58(4):1977-86

PubMed: 24419350 ( click the link to review the publication )

PLoS One, 2014, 9(1):e85463

PubMed: 24416411 ( click the link to review the publication )

PLoS One, 2014, 9(8):e103638

PubMed: 25111382 ( click the link to review the publication )

PLoS One, 2014, 9(11):e112014

PubMed: 25390891 ( click the link to review the publication )

Biomed Res Int, 2014, 2014:764981

PubMed: 25057499 ( click the link to review the publication )

Mod Rheumatol, 2014, 24(5):844-50

PubMed: 24329131 ( click the link to review the publication )

Cancer Lett, 2013, 341(2):224-30

PubMed: 23941832 ( click the link to review the publication )

J Immunol, 2013, 192(1):349-57

PubMed: 24285838 ( click the link to review the publication )

J Cell Physiol, 2013, 228(2):428-38

PubMed: 22740348 ( click the link to review the publication )

Blood, 2012, 120(4):709-19

PubMed: 22337712 ( click the link to review the publication )

J Exp Med, 2012, 209(2):259-73

PubMed: 22271575 ( click the link to review the publication )

Genes Dev, 2012, 26(19):2144-53

PubMed: 22972935 ( click the link to review the publication )

J Infect Dis, 2012, 205(11):1705-8

PubMed: 22474037 ( click the link to review the publication )
J Immunol, 2012, 189(6):2784-92

PubMed: 22904308 ( click the link to review the publication )

J Biol Chem, 2012, 287(20):16835-48

PubMed: 22378792 ( click the link to review the publication )

J Biol Chem, 2012, 287(41):34825-35

PubMed: 22902624 ( click the link to review the publication )

J Cell Physiol, 2012, 228(2):428-438

PubMed: ( click the link to review the publication )

Biochem Biophys Res Commun, 2012, 418(2):234-40

PubMed: 22252297 ( click the link to review the publication )

Blood, 2011, 118(14):3911-21

PubMed: 21821710 ( click the link to review the publication )

Int Immunol, 2011, 23(11):701-12

PubMed: 21937456 ( click the link to review the publication )

Int Immunopharmacol, 2011, 11(12):2242-5

PubMed: 21979495 ( click the link to review the publication )

Chem Biol, 2011, 18(3):314-23

PubMed: 21439476 ( click the link to review the publication )

Biochem Biophy Res Co, 2010, 402(3):500-6

PubMed: 20965150 ( click the link to review the publication )

Purity & Quality Control

Choose Selective JAK Inhibitors

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	Activity Description	PMID
T cells	MX7GeY5kfGmxbjDBd5NigQ>?	MlfqNE4yNzBwMz:xJO69VQ>?	NWLlbGV{OjRiaB?=	NV3zU3cz\Gm\|coXweJMh\|rOlLXPoZYlvKGO7dH;rbY5mKHOrZ37hcIlv\w>?	NYjPfnhQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGzPFMzPDFpPkKxN\|g{OjRzPD;hQi=>
CD4+ T	MYLGeY5kfGmxbjDBd5NigQ>?	MXWxNFAhdk1?	M{\NfVI1NzR6IHi=	MlLUZYJzd2ejdHXzJGNFOy2rbnT1Z4VlKHCqb4PwbI9zgWyjdHnvckBw\iCVVFHUdy=>	MmOxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF6OES1PFAoRjJzOEi0OVgxRC:jPh?=
CD4+ T	Mnq4S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	MYSxNFAwPTByIH7N	MX[0PEBp	NGDPXlRqdmirYnn0d{BidnSrLVPEN{1qdmS3Y3XkJGNFPCwEoGSgZ4VtdCCycn;sbYZmemG2aX;u	MnXnQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF6OES1PFAoRjJzOEi0OVgxRC:jPh?=
CD4+ T	M1SwbWZ2dmO2aX;uJGF{e2G7	MUCyNE8yODBxNUCwJI5O	MVq0PEBp	MoHabY5pcWKrdIOgeIhmKGyndnXsd{Bw\iBiSVytOEwhUU[QLd8zMEBKVC1zN1GgZY5lKEmOLUKy	NGe0R5g9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUi4OFU5OCd-MkG4PFQ2QDB:L3G+
Sf9	Mn;KSpVv[3Srb36gZZN{[Xl?		M4\oVVMxKG2rboO=	M{LzVmlvcGmkaYTpc44hd2ZiaIXtZY4hT1OWLX\1d4VlKEqDS{OgZ4F1[Wy7dHnjJIRwdWGrbjDlfJBz\XO\|ZXSgbY4h[mGldXzveolzfXNvaX7m[YN1\WRiU3[5JINmdGy\|IIXzbY5oKHCxbInncJV1[W2rYzDhZ4llNXS7cn;zbY5mKGG\|IIP1ZpN1emG2ZTDh[pRmeiB\|MDDtbY5{KGK7IFXMTXNCNCCNaTC9JFAvODByNDFOwG0v	NFHBXGY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{[2PFQ5PCd-MkO2Olg1QDR:L3G+
Sf9	Mkn0SpVv[3Srb36gZZN{[Xl?		NYSwb3RpQTBibXnudy=>	M4XlTGlvcGmkaYTpc44hd2ZiaIXtZY4hemWlb33ibY5idnRiTj30[ZJucW6jbDDHV3QufGGpZ3XkJGpCUzNiZYjwdoV{e2WmIHnuJHNnQSClZXzsd{B2e2mwZzDCbY91cW5vTFOtSXFGTEWSRVfEXWZGX0yHIHHzJJN2[nO2cnH0[UBi\nSncjC5NEBucW6\|IHL5JHRTNU[URWSgZZN{[XluIFnDOVAhRSByLkCwNFYh\|ryPLh?=	NVzQZYNyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKwPFc4PTBpPkKyNFg4PzVyPD;hQi=>
Sf9	Mki0SpVv[3Srb36gZZN{[Xl?		M3PaV\|MxKG2rboO=	NFe5RVlKdmirYnn0bY9vKG:oIHj1cYFvKEeVVD3meZNm\CCMQVuxJINifGGueYTpZ{Bld22jaX6g[ZhxemW\|c3XkJIlvKGKjY4Xsc5ZqenW\|LXnu[oVkfGWmIGPmPUBk\WyuczD1d4lv\yCyb3z5[4x2fGGvaXOgZYNq\C22eYLvd4lv\SCjczDzeYJ{fHKjdHWgZYZ1\XJiM{CgcYlveyCkeTDFUGlUSSxiS3mgQUAxNjByMEeg{txONg>?	MlXrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN4Nki0PFQoRjJ\|Nk[4OFg1RC:jPh?=
Sf9	NUjuXmZDTnWwY4Tpc44h[XO\|YYm=		MX:zNEBucW6\|	M1S1PWlvcGmkaYTpc44hd2ZiaIXtZY4hT1OWLX\1d4VlKEqDS{KgZ4F1[Wy7dHnjJIRwdWGrbjDlfJBz\XO\|ZXSgbY4h[mGldXzveolzfXNvaX7m[YN1\WRiU3[5JINmdGy\|IIXzbY5oKHCxbInncJV1[W2rYzDhZ4llNXS7cn;zbY5mKGG\|IIP1ZpN1emG2ZTDh[pRmeiB\|MDDtbY5{KGK7IFXMTXNCNCCNaTC9JFAvODByNzFOwG0v	MlTUQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN4Nki0PFQoRjJ\|Nk[4OFg1RC:jPh?=
Sf9	MkO4SpVv[3Srb36gZZN{[Xl?			MlnaTY5pcWKrdHnvckBw\iCqdX3hckBz\WOxbXLpcoFvfCCJU2SteIFo\2WmIFrINUBld22jaX6gLFc5PSC2b{GxNlUqKG:oIFrBT\|Mh\XiycnXzd4VlKGmwIHnud4VkfCCVZkmgZ4VtdHNiYomgSWxKW0FuIFnDOVAhRSByLkCwNUDPxE1w	Mn\lQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTR3OUOxPFIoRjF2NUmzNVgzRC:jPh?=
Sf9	NXrGUZhKTnWwY4Tpc44h[XO\|YYm=			Ml;yTY5pcWKrdHnvckBw\iCJU2SteIFo\2WmIHj1cYFvKEqDS{OgZ4F1[Wy7dHnjJIRwdWGrbjDlfJBz\XO\|ZXSgbY4hW2Z7IHPlcIx{KGK7IFXMTXNCNCCLQ{WwJF0hOC5yMEGg{txONg>?	MmnvQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzMEW3NVEoRjJzMUC1O\|EyRC:jPh?=
Sf9	NGf6NXhHfW6ldHnvckBie3OjeR?=		NFfEcFQ6OCCvaX7z	M{fnU2lvcGmkaYTpc44hd2ZiaIXtZY4hemWlb33ibY5idnRiTj30[ZJucW6jbDDHV3QufGGpZ3XkJGpCUzFiZYjwdoV{e2WmIHnuJHNnQSClZXzsd{B2e2mwZzDCbY91cW5vTFOtSXFGTEWSRVfEXWZGX0yHIHHzJJN2[nO2cnH0[UBi\nSncjC5NEBucW6\|IHL5JHRTNU[URWSgZZN{[XluIFnDOVAhRSByLkCwN{DPxE1w	NYPDfHBkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKwPFc4PTBpPkKyNFg4PzVyPD;hQi=>
Sf9	MVHGeY5kfGmxbjDhd5NigQ>?			NGLGb\|hKdmirYnn0bY9vKG:oIFfTWE11[WepZXSgbJVu[W5iSlHLN{Bk[XSjbIn0bYMh\G:vYXnuJIV5eHKnc4Pl[EBqdiCVZkmgZ4VtdHNiYomgSWxKW0FuIFnDOVAhRSByLkCwN\|Mh\|ryPLh?=	MlTxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzMEW3NVEoRjJzMUC1O\|EyRC:jPh?=
Sf9	MkXaSpVv[3Srb36gZZN{[Xl?		MV[5NEBucW6\|	NULEfVlvUW6qaXLpeIlwdiCxZjDoeY1idiC{ZXPvcYJqdmGwdDDOMZRmem2rbnHsJGdUXC22YXfn[YQhUkGNMjDlfJBz\XO\|ZXSgbY4hW2Z7IHPlcIx{KHW\|aX7nJGJqd3Srbj3MR{1GWUWGRWDFS2R[TkWZTFWgZZMhe3Wkc4TyZZRmKGGodHXyJFkxKG2rboOgZpkhXFJvRmLFWEBie3OjeTygTWM2OCB;IECuNFA1KM7:TT6=	NXPaXItNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKwPFc4PTBpPkKyNFg4PzVyPD;hQi=>
SF21	MYLGeY5kfGmxbjDhd5NigQ>?		MknUNVAhdWmwcx?=	M2rtbGlvcGmkaYTpc44hd2ZiSlHLNkApfW6tbn;3ckBwemmpaX6pJIV5eHKnc4Pl[EBqdiCVRkKxJINmdGy\|IIXzbY5oKEKrb4Tpck1MSUmHVFTLSXl[XF[NRDDhd{B{fWK\|dILheIUh[W6mIGuzN3Bo[W2vYW3BWHAhcW6ldXLheIVlKG[xcjCxNEBucW6\|IIDybY9zKHSxIIP1ZpN1emG2ZTDh[IRqfGmxbjDt[YF{fXKnZDDh[pRmeiB\|MDDtbY5{KGK7IGTvdINwfW62IHHuZYx6e2m\|LDDJR\|UxKD1iMD6wNFQh\|ryPLh?=	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV2MU[3NEc,OjN3NEG2O\|A9N2F-
insect cells	NYm1O49WTnWwY4Tpc44h[XO\|YYm=			NX7FfZJrUW6qaXLpeIlwdiCxZjDHV3QufGGpZ3XkJGpiczFiZYjwdoV{e2WmIHnuJIlve2WldDDj[YxteyC3c3nu[{A4OCC3TTDBWHAtKEmFNUCgQUAxNjByNkGg{txONg>?	NUDSUnhXRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxOVU3ODVpPkKxNVU2PjB3PD;hQi=>
insect cells	NE\Jc5ZHfW6ldHnvckBie3OjeR?=			MWPJcohq[mm2aX;uJI9nKEeVVD30ZYdo\WRiSnHrN{BmgHC{ZYPz[YQhcW5iaX7z[YN1KGOnbHzzJJV{cW6pIEG4JJVOKEGWUDygTWM2OCB;IECuNFA5KM7:TT6=	MXu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF3NU[wOUc,OjFzNUW2NFU9N2F-
T-cells	MoDISpVv[3Srb36gZZN{[Xl?		Ml\kO\|IhcHK\|	MVLJcohq[mm2aX;uJI9nKEmOMj3pcoR2[2WmIIDyc4xq\mW{YYTpc44hd2ZiaIXtZY4hXCClZXzsd{Bie3Onc4Pl[EBieyCdM1jdeIh6dWmmaX7lJIlv[2:{cH;yZZRqd25iYX\0[ZIhPzJiaILzJIJ6KHOlaX70bYxt[XSrb36gZ492dnSrbnesJGlEPTBiPTCwMlAyOSEQvF2u	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPDV7M{G4Nkc,OTR3OUOxPFI9N2F-
insect cells	NGn5NnBHfW6ldHnvckBie3OjeR?=			Mn7QTY5pcWKrdHnvckBw\iCJU2SteIFo\2WmIFrhb\|Ih\XiycnXzd4VlKGmwIHnud4VkfCClZXzsd{B2e2mwZzCyNEB2VSCDVGCsJGlEPTBiPTCwMlAyOiEQvF2u	MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF3NU[wOUc,OjFzNUW2NFU9N2F-
MO7	NV;Jcm9CTnWwY4Tpc44h[XO\|YYm=			MWDJcohq[mm2aX;uJI9nKEqja{OtcYVlcWG2ZXSgTWwyPS2rbnT1Z4VlKFO2YYS1JJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDNU\|ch[2WubIOgZpkh[2WubD3iZZNm\CCjc4PhfUwhUUN3MDC9JFAvODJ2IN88UU4>	NWLkOm0{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxOVU3ODVpPkKxNVU2PjB3PD;hQi=>
Ba/F3	Mm\DSpVv[3Srb36gZZN{[Xl?		MoP4OlAhdWmwcx?=	NWSwPHNUUW6qaXLpeIlwdiCxZjDUSWwu\nW\|ZXSgTmFMOSCneIDy[ZN{\WRiaX6gRoEwTjNiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBUXEGWNTDwbI9{eGixconsZZRqd25iYX\0[ZIhPjBibXnud{BjgSCDbIDoZXNkemWnbjDhd5NigSxiSVO1NEA:KDBwMEK2JO69VS5?	M4r5W\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MEi3O\|UxLz5{MkC4O\|c2ODxxYU6=
T-cells	NUXVZ5R{TnWwY4Tpc44h[XO\|YYm=			MnyzTY5pcWKrdHnvckBw\iCMQVuzM\|EhcW5iaIXtZY4hXCClZXzsd{BmgHC{ZYPzbY5oKEOGMzDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIFnMNk1{fGmvdXzheIVlKFOWQWS1ZUBxcG:\|cHjvdplt[XSrb36sJGlEPTBiPTCwMlAzQCEQvF2u	MlrOQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3NEC2OFgoRjJ\|NUSwOlQ5RC:jPh?=
PBMC	MonDSpVv[3Srb36gZZN{[Xl?			NFS5dnZKdmirYnn0bY9vKEmOLUetbY5l[3WnZDDTWGFVPSCyaH;zdIhwenmuYYTpc44hcW5iaIXtZY4hWEKPQzDj[YxteyCkeTDmcI94KGO7dH;t[ZRzgSxiSVO1NEA:KDBwMEO5JO69VS5?	Mn7jQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ7Mke0NlMoRjJ4OUK3OFI{RC:jPh?=
TF1	MVvGeY5kfGmxbjDhd5NigQ>?		NWSzVHZ[OjBibXnudy=>	NHnsSIFKdmirYnn0bY9vKG:oIFrBT\|EhcW5iaIXtZY4hXEZzIHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhUUx4LXnu[JVk\WRiU2TBWFMheGixc4Doc5J6dGG2aX;uJIlv[3WkYYTl[EBnd3JiMkCgcYlveyCob3zsc5dm\CCkeTDJUFYh[2ijbHzlcodmKG[xcjCzNEBucW6\|IHnuJJBz\XOnbnPlJI9nKHeqb3zlJIJtd2:mLDDFR\|UxKD1iMD6wOFMh\|ryPLh?=	NXHEXoxJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO2OVkzOTRpPkKzOlU6OjF2PD;hQi=>
TF1	M{D2OmZ2dmO2aX;uJIF{e2G7			Mm\FTY5pcWKrdHnvckBw\iCMQVuxJIlvKGi3bXHuJHRHOSClZXzsd{Bie3Onc4Pl[EBieyC\|dYDwdoV{e2mxbjDv[kBKVDZvc4TpcZVt[XSnZDDTWGFVOyCyaH;zdIhwenmuYYTpc44h[nliQXzwbIFU[3KnZX6gZZN{[XluIFnOTEA:KDBwMES1JO69VS5?	NHLsdFQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkO3NlY2Oyd-Mk[zO\|I3PTN:L3G+
CTLL	MlTySpVv[3Srb36gZZN{[Xl?			Mn;DTY5pcWKrdHnvckBw\iCMYXuzMY1m\GmjdHXkJGlNOi2rbnT1Z4VlKFO2YYS1JJBpd3OyaH;yfYxifGmxbjDpckBud3W\|ZTDDWGxNKGOnbHzzJIJ6KGOnbHytZoF{\WRiYYPzZZktKEmFNUCgQUAxNjB2ODFOwG0v	NGLTdnk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUG1OVYxPSd-MkGxOVU3ODV:L3G+
Sf9	Ml7wSpVv[3Srb36gZZN{[Xl?		NITPfGg6OCCvaX7z	NHvlNJVKdmirYnn0bY9vKG:oIHj1cYFvKHKnY3;tZolv[W62IF6teIVzdWmwYXygS3NVNXSjZ3fl[EBVYUt{IHX4dJJme3OnZDDpckBU\jliY3XscJMhfXOrbnegRolwfGmwLVzDMWVSTUSHUFXHSHlHTVeORTDhd{B{fWK\|dILheIUh[W[2ZYKgPVAhdWmwczDifUBVWi2IUlXUJIF{e2G7LDDJR\|UxKD1iMD6wOVIh\|ryPLh?=	MYi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjB6N{e1NEc,OjJyOEe3OVA9N2F-
TF1	NWizUIlDTnWwY4Tpc44h[XO\|YYm=			NGHwdndKdmirYnn0bY9vKG:oIFrBT\|EhcW5iaIXtZY4hXEZzIHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhUUx{LXnu[JVk\WRiU2TBWFMheGixc4Doc5J6dGG2aX;uMEBGSzVyIE2gNE4xPTNizszNMi=>	MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjV7MUSwNkc,OjJ3OUG0NFI9N2F-
TF1	MYnGeY5kfGmxbjDhd5NigQ>?		NI\nSWEzOCCvaX7z	MWfJcohq[mm2aX;uJI9nKEqDS{GgbY4hcHWvYX6gWGYyKGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gTWw3NWmwZIXj[YQhW1SDVEOgdIhwe3Cqb4L5cIF1cW:wIHnuZ5Vj[XSnZDDmc5IhOjBibXnud{BxemmxcjD0c{BKVDZvaX7keYN1cW:wIH3lZZN2emWmIHHmeIVzKDNyIITvJFQ2KG2rboOsJGVEPTBiPTCwMlA2OyEQvF2u	MVi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjZ7OEC4OEc,OjJ4OUiwPFQ9N2F-
TF1	Ml:5SpVv[3Srb36gZZN{[Xl?		NXj5d4ZZOjBibXnudy=>	MoflTY5pcWKrdHnvckBw\iCMQVuxJIlvKGi3bXHuJHRHOSClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGlNPi2rbnT1Z4VlKFOWQWSzJJBpd3OyaH;yfYxifGmxbjDpcoN2[mG2ZXSg[o9zKDJyIH3pcpMh\m:ubH;3[YQh[nliSVy2JINp[WyuZX7n[UBnd3JiM{CgcYlveyxiRVO1NEA:KDBwMEWzJO69VS5?	MnPVQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN4NUmyNVQoRjJ\|NkW5NlE1RC:jPh?=
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T-cells	Mlm4SpVv[3Srb36gZZN{[Xl?			M{LsUWlvcGmkaYTpc44hd2ZiYXzsc4dmdmmlIHPlcIx{NXO2aX31cIF1\WRicILvcIln\XKjdHnvckBqdiCvb37r[ZkhXCClZXzsd{BjgSCvaYjl[EBtgW2yaH;jfZRmKHKnYXP0bY9vKG2ndHjv[EwhUUN3MDC9JFAvODV5IN88UU4>	NWrQdnpRRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUS1PVMyQDJpPkG0OVk{OTh{PD;hQi=>
CD34+	NWfpOFNNTnWwY4Tpc44h[XO\|YYm=			NIS4e5dKdmirYnn0bY9vKG:oIFrBT\|IhcW5iaIXtZY4hS0R\|NDugZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iCHUF:tcYVlcWG2ZXSgZ4VtdCCycn;sbYZmemG2aX;uMEBKSzVyIE2gNE4xPzFizszNMi=>	Mk\vQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ7Mke0NlMoRjJ4OUK3OFI{RC:jPh?=
TF1	MUfGeY5kfGmxbjDhd5NigQ>?			NXK4dHFmUW6qaXLpeIlwdiCxZjDJUFQucW6mdXPl[EBxem:uaX\ldoF1cW:wIH;mJHRHOSClZXzsd{whUUN3MDC9JFAvODhizszNMi=>	MnrKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTZ7M{S0OVcoRjF4OUO0OFU4RC:jPh?=
T-cells	NXPOXVNYTnWwY4Tpc44h[XO\|YYm=			MXjJcohq[mm2aX;uJI9nKGGubH;n[Y5q[yClZXzsd{1{fGmvdXzheIVlKHC{b3zp[oVz[XSrb36gbY4hcHWvYX6gWEBk\WyuczDifUBucXinZDDsfY1xcG:leYTlJJJm[WO2aX;uJI1mfGixZDygTWM2OCB;IECuNFg4KM7:TT6=	M{\qPFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF2NUmzNVgzLz5zNEW5N\|E5OjxxYU6=
TF1	MoHiSpVv[3Srb36gZZN{[Xl?		NUC1UnVyOjBibXnudy=>	MWPJcohq[mm2aX;uJI9nKEqDS{KgbY4hcHWvYX6gWGYyKGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gSXBQNWmwZIXj[YQhW1SDVEWgdIhwe3Cqb4L5cIF1cW:wIHnuZ5Vj[XSnZDDmc5IhOjBibXnud{BxemmxcjD0c{BGWE9vaX7keYN1cW:wIH3lZZN2emWmIHHmeIVzKDNyIITvJFQ2KG2rboOsJGVEPTBiPTCwMlA6OyEQvF2u	Mnq4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ4OUiwPFQoRjJ{Nkm4NFg1RC:jPh?=
TF1	MYXGeY5kfGmxbjDhd5NigQ>?		M17JW\|IxKG2rboO=	NIjJ[JVKdmirYnn0bY9vKG:oIFrBT\|IhcW5iaIXtZY4hXEZzIHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhTVCRLXnu[JVk\WRiU2TBWFUheGixc4Doc5J6dGG2aX;uJIlv[3WkYYTl[EBnd3JiMkCgcYlveyCob3zsc5dm\CCkeTDJUFYh[2ijbHzlcodmKG[xcjCzNEBucW6\|LDDFR\|UxKD1iMD6wPVMh\|ryPLh?=	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzZ3OUKxOEc,OjN4NUmyNVQ9N2F-
PBMC	NIDTVW1HfW6ldHnvckBie3OjeR?=			NGf2Nm1KdmirYnn0bY9vKG:oIFrBT\|EhcW5iaIXtZY4hWEKPQzDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKEmOLU[tbY5lfWOnZDDNR3AyKHOnY4LleIlwdixiSVO1NEA:KDBwMEm1JO69VS5?	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjl{N{SyN{c,OjZ7Mke0NlM9N2F-
TF1	NWLS[GoxTnWwY4Tpc44h[XO\|YYm=		NGLiToMzKGi{cx?=	NUXubWp3UW6qaXLpeIlwdiCxZjDKRWszKGmwIFfNR3NHNXO2aX31cIF1\WRiaIXtZY4hXEZzIHPlcIx{KGG\|c3Xzd4VlKGG\|IIP1dJBz\XO\|aX;uJI9nKFOWQWS1JJBpd3OyaH;yfYxifGmxbjDwdoVqdmO3YnH0[YQh\m:{IEKgbJJ{KG[xbHzve4VlKGK7IFfNR3NHKHO2aX31cIF1cW:wIH\vdkA2OCCvaX7zJIJ6KE[DQ2OgdoVi\GW{IHHuZYx6e2m\|LDDJR\|UxKD1iMD6wPVUh\|ryPLh?=	M2HjflxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5MUOwN\|U6Lz5{N{GzNFM2QTxxYU6=
TF1	MmriSpVv[3Srb36gZZN{[Xl?			M3[zdGlvcGmkaYTpc44hd2ZiSlHLNkBqdiCHUF:td5RqdXWuYYTl[EBpfW2jbjDUSlEh[2WubIOg[ZhxemW\|c3nu[{B{fGGkbImgbY51\We{YYTl[EBj\XSjLXzhZ5RidWG\|ZTDy[ZBwenSncjDn[Y5mKHWwZHXyJINwdnS{b3ygc4YhW1SDVEWgdoV{eG:wc3Wg[YxmdWWwdIOgbY4hcW62ZYLm[ZJwdiC{ZXf1cIF1d3K7IH\hZ5RweiBzIHflcoUheHKxbX;0[ZIh[nliZnz1c5Jme2OnbnPlJIF{e2G7LDDJR\|UxKD1iMD6xNFch\|ryPLh?=	M3vrZ\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7MUW2NVM3Lz5{OUG1OlE{PjxxYU6=
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T-cells	M3zQemZ2dmO2aX;uJIF{e2G7			MXvJcohq[mm2aX;uJI9nKGGubH;n[Y5q[yClZXzsd{1{fGmvdXzheIVlKHC{b3zp[oVz[XSrb36gbY4hdW:3c3WgWEBk\WyuczDifUBucXinZDDsfY1xcG:leYTlJJJm[WO2aX;uJI1mfGixZDygTWM2OCB;IECuNVE2KM7:TT6=	M1TiWlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF2NUmzNVgzLz5zNEW5N\|E5OjxxYU6=
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CTLL-2	MULBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		NYmxRpBwPzJiaILz	MX\BcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IFnMMVIue3SrbYXsZZRm\CCvb4Xz[UBEXEyOLUKgZ4VtdHNiZYjwdoV{e2mwZzDKRWsyN0qDS{OgZYZ1\XJiN{KgbJJ{KGK7IHHsZY1ieiCkbIXlJIF{e2G7LDDJR\|UxKD1iMD6xN\|Ih\|ryPLh?=	MkXaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTl5NkKyN\|goRjF7N{[yNlM5RC:jPh?=
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DND/L12	NYfnWHBLTnWwY4Tpc44h[XO\|YYm=		NV3XR5Z5OzBibXnudy=>	Ml;JTY5pcWKrdHnvckBw\iCMQVuzJIlvKGi3bXHuJGRPTC:OMUKgZ4VtdHNiYX\0[ZIhOzBibXnud{BjgSCudXPp[oVz[XOnIHHzd4F6KGmwIIDy[ZNmdmOnIH;mJIh2dWGwIIPldpVuKGGuYoXtbY4tKEmFOUCgQUAxNjF4IN88UU4>	MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPDV7M{G4Nkc,OTR3OUOxPFI9N2F-
T-cells	NEfhZZVHfW6ldHnvckBie3OjeR?=			Mnu4TY5pcWKrdHnvckBw\iCMQVuyM\|EhcW5iaIXtZY4hXCClZXzsd{BmgHC{ZYPzbY5oKEOGMzDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIFnGUodidW2jLYP0bY12dGG2ZXSgV3RCXDFicHjvd5Bpd3K7bHH0bY9vNCCLQ{WwJF0hOC5zNzFOwG0v	M4r1PFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NUSwOlQ5Lz5{M{W0NFY1QDxxYU6=
insect	MVXGeY5kfGmxbjDhd5NigQ>?			M2HxN2lvcGmkaYTpc44hd2ZiR2PUMZRi\2enZDDUfYszKGW6cILld5Nm\CCrbjDpcpNm[3RiY3XscJMhfXOrbnegN\|UhfU1iQWTQMEBKSzVyIE2gNE4yPzZizszNMi=>	MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF3NU[wOUc,OjFzNUW2NFU9N2F-
Ba/F3	MXzGeY5kfGmxbjDhd5NigQ>?		M4LzO\|YxKG2rboO=	NH3Bb2JKdmirYnn0bY9vKG:oIGTFUE1nfXOnZDDKRWszKGW6cILld5Nm\CCrbjDCZU9HOyClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJHNVSVR3IIDoc5NxcG:{eXzheIlwdiCjZoTldkA3OCCvaX7zJIJ6KEGucHjhV4Nz\WWwIHHzd4F6NCCLQ{WwJF0hOC5{NkWg{txONg>?	NWfN[Xd7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKwPFc4PTBpPkKyNFg4PzVyPD;hQi=>
TF1	M1HO[GZ2dmO2aX;uJIF{e2G7			NGfwc3ZKdmirYnn0bY9vKG:oIFrBT\|IhcW5iaIXtZY4hXEZzIHPlcIx{KGG\|c3Xzd4VlKGG\|IIP1dJBz\XO\|aX;uJI9nKGOnbHyg[5Jwf3SqLDDJR\|UxKD1iMD6yO\|UyKM7:TT6=	NITkVos9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{e3NVE5OCd-Mke3O\|EyQDB:L3G+
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HUO3	M{Hlb2Z2dmO2aX;uJIF{e2G7		M2i0PFQh\GG7cx?=	MV3Jcohq[mm2aX;uJI9nKGi3bXHuJGdONUOVRj3pcoR2[2WmIIDyc4xq\mW{YYTpc44hcW5iaIXtZY4hUFWRMzDj[YxteyCjc4Pld5Nm\CCjczDbN2hefGi7bXnkbY5mKGmwY3;ydI9z[XSrb36gZYZ1\XJiNDDkZZl{KGK7IIPjbY51cWyuYYTpc44h[2:3boTpcoctKEmFNUCgQUAxNjN{NDFOwG0v	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPDV7M{G4Nkc,OTR3OUOxPFI9N2F-
HU03	MkDmSpVv[3Srb36gZZN{[Xl?		NWHySYJTPzJiaILz	MknmTY5pcWKrdHnvckBw\iCJTT3DV2YucW6mdXPl[EBpfW2jbjDIWVA{KGOnbHzzJJBzd2yrZnXyZZRqd25iYX\0[ZIhPzJiaILzJIJ6KFt\|SG30bJlucWSrbnWgbY5kd3Kyb4LheIlwdiCjc4PhfUwhUUN3MDC9JFAvOzJ2IN88UU4>	MmXPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzMEW3NVEoRjJzMUC1O\|EyRC:jPh?=
BAF3	NEHCS5RCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NHzUXnc4OiCqcoO=	MYnBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IH3veZNmKEKDRkOgZ4VtdHNiZYjwdoV{e2mwZzDUSWwuUkGNMzDrbY5ie2ViYX\0[ZIhPzJiaILzJIJ6KGGuYX3hdkBjdHWnIHHzd4F6NCCLQ{WwJF0hOC53NzFOwG0v	NUKxbmRQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUm3OlIzOzhpPkG5O\|YzOjN6PD;hQi=>
T-cells	MWfGeY5kfGmxbjDhd5NigQ>?		MmDKN{Bl[Xm\|	NV7vW2lHUW6qaXLpeIlwdiCxZjDj[YxtKHC{b3zp[oVz[XSrb36gc4YhUUx{LXHjeIl3[XSnZDDhcoQhS0R\|IHHu[EBETDJ6IHHueIljd2S7LYP0bY12dGG2ZXSgcY92e2ViQ1S0MZBwe2m2aY\lJHQh[2WubIOgZYZ1\XJiMzDkZZl{KGK7IGjUWEBie3OjeTygTWM2OCB;IECuOlMh\|ryPLh?=	MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODR4MEi0Nkc,OzB2NkC4OFI9N2F-
NK92	M13lVWZ2dmO2aX;uJIF{e2G7		MXOyNEBucW6\|	MnG3TY5pcWKrdHnvckBw\iCWWVuyJIlvKGi3bXHuJG5MQTJiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBKVDF{LXnu[JVk\WRiU2TBWFQheGixc4Doc5J6dGG2aX;uJIlv[3WkYYTl[EBnd3JiMkCgcYlveyCob3zsc5dm\CCkeTDJUFEzKGOqYXzs[Y5o\SCob4KgOFUhdWmwczygSWM2OCB;IECuO\|Eh\|ryPLh?=	MXK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzZ3OUKxOEc,OjN4NUmyNVQ9N2F-
TF1	M4XNZWZ2dmO2aX;uJIF{e2G7			MonjTY5pcWKrdHnvckBw\iCLTEOtbY5lfWOnZDDwdo9tcW[ncnH0bY9vKG:oIGTGNUBk\WyuczygTWM2OCB;IECuPEDPxE1w	MUe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPjl\|NES1O{c,OTZ7M{S0OVc9N2F-
UT7	MmTGSpVv[3Srb36gZZN{[Xl?			M1ixPWlvcGmkaYTpc44hd2ZiSlHLNkBqdiCqdX3hckBWXDdiY3XscJMh[XO\|ZYPz[YQh[XNic4XwdJJme3Orb36gc4YhTVCRLYP0bY12dGG2ZXSgV3RCXDVicHjvd5Bpd3K7bHH0bY9vKGK7IFHsdIhiW2O{ZXXuJIF{e2G7LDDJUmghRSBzLkGyJO69VS5?	NVO1PJBWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[zO\|I3PTNpPkK2N\|czPjV\|PD;hQi=>
Ba/F3	M2rVNmZ2dmO2aX;uJIF{e2G7		NFrKN403OCCvaX7z	M13sNmlvcGmkaYTpc44hd2ZiVFXMMYZ2e2WmIGTZT\|Ih\XiycnXzd4VlKGmwIFLhM2Y{KGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gV3RCXDVicHjvd5Bpd3K7bHH0bY9vKGGodHXyJFYxKG2rboOgZpkhSWyyaHHTZ5Jm\W5iYYPzZZktKEmFNUCgQUAyNjJizszNMi=>	MkftQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJyOEe3OVAoRjJ{MEi3O\|UxRC:jPh?=
T-cells	MVvGeY5kfGmxbjDhd5NigQ>?		NFTve3U4OiCqcoO=	NUWxWpBRUW6qaXLpeIlwdiCxZjDKRWs{KGmwIILheEB{eGynbn;jfZRq[yCWIHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDpckBKVC1{LXnu[JVk\WRiY3XscEBxem:uaX\ldoF1cW:wIHHmeIVzKDd{IHjyd{BjgSCPVGOgZZN{[XluIFnDOVAhRSBzLkKg{txONg>?	NWTZOVV[RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{CxN\|k2PzVpPkOwNVM6PTd3PD;hQi=>
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HEL	MWTGeY5kfGmxbjDhd5NigQ>?		M1;ud\|EhcHJ?	M{HiN2lvcGmkaYTpc44hd2ZiSlHLNkBXPjF5RjDteZRidnRiaX6gbJVu[W5iSFXMJINmdGy\|IHHmeIVzKDFiaIKsJGlEPTBiPTC0MlczPCEQvF2u	M{fvUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5N{exNVgxLz5{N{e3NVE5ODxxYU6=
Jurkat	MX\GeY5kfGmxbjDhd5NigQ>?		MVuyOEBpenN?	MWXJcohq[mm2aX;uJI9nKGGwdHmtR2Q{N2GwdHmtR2QzQC2rbnT1Z4VlKEmOMjDwdo9lfWO2aX;uJIlvKGi3bXHuJGp2emujdDDj[YxteyCjZoTldkAzPCCqcoOgZpkhe2OrboTpcIxifGmxbjDjc5VvfGmwZzygTWM2OCB;IEeuPFQh\|ryPLh?=	MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPDV7M{G4Nkc,OTR3OUOxPFI9N2F-
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T-cells	M{\IbmZ2dmO2aX;uJIF{e2G7	MVy1JJRwKDVyMDDuUS=>	NEn0NYMyKGi{	NU\CcplzUW6qaXLpeIlwdiCxZjDJUFIucW6mdXPl[EBUfGG2NTDwbI9{eGixconsZZRqd25iaX6gbJVu[W5iQ1S0L{BVKGOnbHzzJIF1KDVidH:gOVAxKG6PIHHmeIVzKDFiaIKgZpkhX2W\|dHXyckBjdG:2	MofwQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTlyNUO3OVYoRjF7MEWzO\|U3RC:jPh?=
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T-cells	MULGeY5kfGmxbjDhd5NigQ>?	NVnDW\|NwPTBidH:gN\|AxKG6P	NHH5NlYyKGi{	M1zT[mlvcGmkaYTpc44hd2ZiSlHLNU9LSUt\|IHnuJIh2dWGwIFPEOEBxd3OrdHn2[UBVKGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gTWw1NXO2aX31cIF1\WRiU2TBWFYheGixc4Doc5J6dGG2aX;uJIF1KDVyIITvJFMxOCCwTTDwdoVqdmO3YnH0[YQh\m:{IEGgbJIh\m:ubH;3[YQh[nliSVytOEB{fGmvdXzheIlwdiCvZXHzeZJm\CCjZoTldkA{OCCvaX7zJIJ6KGmvbYXuc4Jtd3RiYX7hcJl{cXN?	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTh3MkC2PEc,Ojl6NUKwOlg9N2F-
T-cells	MlS5SpVv[3Srb36gZZN{[Xl?	MV21NEB1dyB\|MECgcm0>	MkPkNUBpeg>?	NHjESJpKdmirYnn0bY9vKG:oIFrBT\|EwUkGNMzDpckBpfW2jbjDDSFQheG:\|aYTpeoUhXCClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGlNOi2\|dHnteYxifGWmIGPURXQ2KHCqb4PwbI9zgWyjdHnvckBifCCWeYKtOlk2KHKnc3nkeYUh[XRiNUCgeI8hOzByIH7NJJBz\WmwY4XiZZRm\CCob4KgNUBpeiCob3zsc5dm\CCkeTDJUE0zKHO2aX31cIF1cW:wIH3lZZN2emWmIHHmeIVzKDNyIH3pcpMh[nliaX3teY5w[myxdDDhcoFtgXOrcx?=	MkDDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl6NUKwOlgoRjJ7OEWyNFY5RC:jPh?=
T-cells	MWrGeY5kfGmxbjDhd5NigQ>?	MojBQlMxOCCwTR?=	M{nrR\|EhcHJ?	MYjJcohq[mm2aX;uJI9nKEqDS{GvTmFMOi:WWVuyJIlvKGi3bXHuJGNFPCCyb4PpeIl3\SCWIHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhUUx4LYP0bY12dGG2ZXSgV3RCXDNicHjvd5Bpd3K7bHH0bY9vKGG2IE6zNFAhdk1icILlbY5kfWKjdHXkJIZweiBzIHjyJIZwdGyxd3XkJIJ6KEmOLU[gd5RqdXWuYYTpc44hdWWjc4Xy[YQh[W[2ZYKgN\|AhdWmwczDifUBqdW23bn;icI91KGGwYXz5d4l{	MnS0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl6NUKwOlgoRjJ7OEWyNFY5RC:jPh?=
TALL-1	M3q1VmZ2dmO2aX;uJIF{e2G7	NIGzV2MyKHWP	MX:zJIhzew>?	NVfKdFBSUW6qaXLpeIlwdiCxZjDKRWs{KGmwIHj1cYFvKFSDTFytNUBk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIFnMMVIhcW6mdXPl[EBUXEGWNTDwbI9{eGixconsZZRqd25iYYSgNUB2VSCycnXpcoN2[mG2ZXSg[o9zKDNiaILzJIZwdGyxd3XkJIJ6KEmOLUKgbY5lfWO2aX;uJI1m[XO3cnXkJIFnfGW{IEOwJI1qdnNiYomgbY1ufW6xYnzveJRqdmd?	M4PaOlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MkW4OVIyLz5{NkK1PFUzOTxxYU6=
BA/F3	Mm\ESpVv[3Srb36gZZN{[Xl?	NHLGeGI{ODBibl2=	MUSzJIhzew>?	MnKyTY5pcWKrdHnvckBw\iCMQVuzJEh2dmuwb4fuJI9zcWerbjmg[ZhxemW\|c3XkJIlvKG2xdYPlJGJCN0Z\|IHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDv[kBUXEGWNTDwbI9{eGixconsZZRqd25iYYSgN\|AxKG6PIHHmeIVzKDNiaILzJIJ6KGmvbYXuc4Jtd3S2aX7nJIFv[Wy7c3nz	MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjJ3OEWyNUc,OjZ{NUi1NlE9N2F-
OCL-AML5	NELTdWdHfW6ldHnvckBie3OjeR?=	M3ryW\|EhfU1?	NFf3[Gg{KGi{cx?=	Mn7MTY5pcWKrdHnvckBw\iCMQVuyJIlvKGi3bXHuJG9EVC2DTVy1JINmdGy\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiR12tR3NHKGmwZIXj[YQhW1SDVEWgdIhwe3Cqb4L5cIF1cW:wIHH0JFEhfU1icILlbY5kfWKjdHXkJIZweiB\|IHjyd{Bnd2yub4fl[EBjgSCJTT3DV2YhcW6mdXP0bY9vKG2nYYP1doVlKGGodHXyJFMxKG2rboOgZpkhcW2vdX7vZoxwfHSrbne=	NXT4[nR3RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[yOVg2OjFpPkK2NlU5PTJzPD;hQi=>
BA/F3	M2Pob2FvfGmycn;sbYZmemG2aY\lJIF{e2G7		MX[3NkBpenN?	Mn3TRY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6\|dDDtc5V{\SCEQT;GN{Bk\WyuczDlfJBz\XO\|aX7nJHRGVC2MQVuzJIFnfGW{IEeyJIhzeyCkeTDj[YxtKHSrdHXyJIdtdyCjc4PhfS=>	MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjJ3OEWyNUc,OjZ{NUi1NlE9N2F-
BA/F3	NInKZmVHfW6ldHnvckBie3OjeR?=	MXKxJJVO	M3rZcFMhcHK\|	NIC2UZJKdmirYnn0bY9vKG:oIFrBT\|MhMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5ibX;1d4UhSkFxRkOgZ4VtdHNiYYSgNUB2VSCycnXpcoN2[mG2ZXSg[o9zKDNiaILzJIZwdGyxd3XkJIJ6KHC3bHzkc5dvKHerdHigd5Rz\XC2YY\p[IlvKGKnYXTzJIJ6KGmvbYXuc4Jtd3S2aX7nJIFv[Wy7c3nz	M3TqOVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MkW4OVIyLz5{NkK1PFUzOTxxYU6=
Huh7	NH;VR5pHfW6ldHnvckBie3OjeR?=	MlPBNVAhfU1?	M1W1bVMxKG2rboO=	MoToTY5pcWKrdHnvckBw\iCWeXuyJIlvKGi3bXHuJGh2cDdiY3XscJMh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIH;mJGlHVmGucHjhOU1qdmS3Y3XkJHNVSVR\|IIDoc5NxcG:{eXzheIlwdiCjdDCxNEB2VSCycnWtbY5kfWKjdHXkJIZweiB\|MDDtbY5{KGKnZn;y[UBKTk6jbIDoZVUhe3SrbYXsZZRqd25iZn;yJFMxKG2rboOgcYlveyCkeTDpcY12dm:kbH;0eIlv\w>?	M3LrWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MkOxNVU6Lz5{NkKzNVE2QTxxYU6=
Huh7	NVnWWYVPTnWwY4Tpc44h[XO\|YYm=	M4flZlExKHWP	MlPWN\|AhdWmwcx?=	M1\iPWlvcGmkaYTpc44hd2ZiVInrNkBqdiCqdX3hckBJfWh5IHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDv[kBj[XOjbDDs[ZZmdCCVVFHUN{BxcG:\|cHjvdplt[XSrb36gZZQhOTBidV2gZYZ1\XJiM{CgcYlveyCkeTDpcY12dm:kbH;0eIlv\w>?	MlTzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ{M{GxOVkoRjJ4MkOxNVU6RC:jPh?=
Huh7	MlWwSpVv[3Srb36gZZN{[Xl?	M2\ifVEhfU1?	NHnOUnk{OCCvaX7z	M{nOOGlvcGmkaYTpc44hd2ZiVInrNkBqdiCqdX3hckBJfWh5IHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDv[kBKTk6jbIDoZVUucW6mdXPl[EBUXEGWMzDwbI9{eGixconsZZRqd25iYYSgNUB2VSCycnWtbY5kfWKjdHXkJIZweiB\|MDDtbY5{KGKnZn;y[UBKTk6jbIDoZVUhe3SrbYXsZZRqd25iZn;yJFMxKG2rboOgcYlveyCkeTDpcY12dm:kbH;0eIlv\w>?	NHG1ZXc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkKzNVE2QSd-Mk[yN\|EyPTl:L3G+

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	JAK3 / STAT5 / p-STAT5 ; PubMed: 27732937 Oncotarget The following cell lines: EBV-negative B cell line (BJAB), EBV-transformed lymphoblastoid cell line (LCL), EBV-negative T cell lines (Jurkat and MOLT4), EBV-positive T cell lines (SNT15 and SNT16), EBV-negative NK cell line (KHYG1), and EBV-positive NK cell lines (KAI3 and SNK6), were treated without (−) or with (+) 1 μM tofacitinib for 24 h and cell lysates were then immunoblotted for the indicated proteins. LMP1 / EBNA1 / BZLF1 ; PubMed: 27732937 Oncotarget SNT13, SNT15, SNT16, KAI3 and SNK6 cell lines were treated with 5 μM tofacitinib for 48 h, and cell lysates were immunoblotted for LMP1, EBNA1 and BZLF1. Actin was blotted as a loading control. JAK3 / p-JAK3 / STAT3 ; PubMed: 26082451 Blood CTCL cell lines were subjected to western blot (tofacitinib 10, 100, 200 nM) (G) after 48 hours of treatment.	27732937 26082451
Growth inhibition assay	Cell number ; PubMed: 27732937 Oncotarget BJAB, LCL, Jurkat, SNT15, KHYG1 and KAI3 cells were treated with the indicated concentrations of tofacitinib, and viable cells were counted at the indicated times using the trypan blue exclusion test. Values are means ± SE of the results from triplicate experiments. *P < 0.05 as compared with DMSO-treated cells.	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

Kinase Assay: ^[1]	- Collapse 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]	- Collapse 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. (Only for Reference)
Animal Research: ^[1]	- Collapse Animal Models: DBA/2 and C57/BL6 mice Dosages: 0-136 ng/mL Administration: Administered via osmotic minipump infusion (Only for Reference)

References

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Solubility (25°C)

In vitro	DMSO	62 mg/mL warmed (198.48 mM)
	Water	Insoluble
	Ethanol	Insoluble
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.	5mg/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 Download Tofacitinib (CP-690550) SDF

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

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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.

Note：1.Please make sure the liquid is clear before adding the next solvent.
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C1=C0/X	C1:	LOG(C1):
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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2021-01-06)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT04496960	Not yet recruiting	Drug: tofacitinib\|Other: Placebo	Sjogren''s Syndrome	National Institute of Dental and Craniofacial Research (NIDCR)\|National Institutes of Health Clinical Center (CC)	January 5 2021	Phase 1\|Phase 2
NCT04624230	Not yet recruiting	Drug: tofacitinib	Ulcerative Colitis	Pfizer	November 20 2020	Phase 3
NCT04468425	Not yet recruiting	Drug: Tofacitinib Citrate	Healthy Subjects	TWi Biotechnology Inc.	November 11 2020	Phase 1
NCT04424303	Not yet recruiting	Drug: Tofacitinib	Ulcerative Colitis	Pfizer	September 30 2020	--
NCT04576000	Recruiting	Drug: Tofacitinib	Ulcerative Colitis	Robarts Clinical Trials Inc.	August 25 2020	--
NCT04141904	Suspended	Drug: Tofacitinib 5 MG [Xeljanz]\|Other: Placebo	Depression\|Inflammation	University of Oxford\|Wellcome Trust\|Medical Research Council	February 10 2020	Phase 1\|Phase 2

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.

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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.

JAK Signaling Pathway Map

JAK Inhibitors with Unique Features

Selective JAK Inhibitor

Fedratinib (SAR302503, TG101348) : JAK2-selective, IC50=3 nM.
Most Potent JAK Inhibitor

AZD1480 : JAK2, IC50=0.26 nM.
FDA-approved JAK Inhibitor

Tofacitinib (CP-690550,Tasocitinib) : Approved by FDA for rheumatoid arthritis (RA).
Newest JAK Inhibitor

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

Related JAK Products

FLLL32 ^New

FLLL32 is a potent JAK2/STAT3 inhibitor with IC50 of <5 μM. FLLL32 inhibits the induction of STAT3 phosphorylation by IFNα and IL-6 in breast cancer cells.
Cerdulatinib (PRT062070) hydrochloride ^New

Cerdulatinib (PRT-062070, PRT2070) hydrochloride is an oral active, multi-targeted tyrosine kinase inhibitor with IC50 of 12 nM/6 nM/8 nM/0.5 nM and 32 nM for JAK1/JAK2/JAK3/TYK2 and Syk, respectively. Also inhibits 19 other tested kinases with IC50 less than 200 nM.
Ruxolitinib (INCB018424)

Ruxolitinib (INCB018424) is the first potent, selective, JAK1/2 inhibitor to enter the clinic with IC50 of 3.3 nM/2.8 nM in cell-free assays, >130-fold selectivity for JAK1/2 versus JAK3. Ruxolitinib kills tumor cells through toxic mitophagy. Ruxolitinib induces autophagy and enhances apoptosis.
Tofacitinib (CP-690550) Citrate

Tofacitinib citrate (CP-690550, Tasocitinib) is a novel inhibitor of JAK with IC50 of 1 nM, 20 nM and 112 nM against JAK3, JAK2, and JAK1, respectively. Tofacitinib citrate has anti-infection activity.
AZD1480

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.
Fedratinib (TG101348)

Fedratinib (SAR302503, TG101348) is a selective inhibitor of JAK2 with IC50 of 3 nM in cell-free assays, 35- and 334-fold more selective for JAK2 versus JAK1 and JAK3. Fedratinib also inhibits FMS-like tyrosine kinase 3 (FLT3) and RET (c-RET) with IC50 of 15 nM and 48 nM, respectively. Fedratinib has potential antineoplastic activity. Fedratinib inhibits proliferation and induces apoptosis. Phase 2.
Momelotinib (CYT387)

Momelotinib (CYT387, LM-1149 , CYT11387) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, ~10-fold selectivity versus JAK3. Momelotinib (CYT387) induces apoptosis and autophagy. Phase 3.
WP1066

WP1066 is a novel inhibitor of JAK2 and STAT3 with IC50 of 2.30 μM and 2.43 μM in HEL cells; shows activity to JAK2, STAT3, STAT5, and ERK1/2 not JAK1 and JAK3. WP1066 induces apoptosis. Phase 1.

Features:Similar to its parent compound AG490, WP1066 inhibits the phosphorylation of JAK2, but unlike AG490, WP1066 also degraded JAK2 protein.
Baricitinib (INCB028050)

Baricitinib (LY3009104, INCB028050) is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM in cell-free assays, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2. Baricitinib is found to reduce or interrupt the passage of the virus into target cells and is used in the treatment research for COVID-19. Phase 3.

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Tofacitinib (CP-690550)