Tofacitinib (CP-690550)

Name: Tofacitinib (CP-690550)
Brand: Selleck Chemicals
SKU: S2789
Rating: 5 (119 reviews)

For research use only.

Licensed by Pfizer Catalog No.S2789 Synonyms: Tasocitinib

119 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 119 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 )

Cancer Lett, 2021, 510:37-47

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

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J Clin Med, 2021, 10(7)1431

PubMed: 33916057 ( click the link to review the publication )

Cell Chem Biol, 2021, S2451-9456(21)00303-2

PubMed: 34216546 ( click the link to review the publication )

Sci Rep, 2021, 11(1):9561

PubMed: 33953256 ( click the link to review the publication )

Int J Biol Macromol, 2021, 185:907-916

PubMed: 34242647 ( click the link to review the publication )

Clin Exp Rheumatol, 2021, 39 Suppl 129(2):161-170

PubMed: 34014157 ( click the link to review the publication )

Eur J Pharmacol, 2021, 906:174214

PubMed: 34116044 ( click the link to review the publication )

Platelets, 2021, 1-12

PubMed: 34097573 ( click the link to review the publication )

J Immunol Methods, 2021, 493:113020

PubMed: 33705736 ( 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 Immunol, 2017, 198(2):657-668

PubMed: 27940659 ( 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 )

Oncotarget, 2016, 7(12):13886-901

PubMed: 26883104 ( 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 )

Cell Signal, 2014, 26(1):149-61

PubMed: 24140475 ( 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 )

Transplantation, 2013, 95(3):448-55

PubMed: 23274966 ( 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	MYHGeY5kfGmxbjDBd5NigQ>?	MlXTNE4yNzBwMz:xJO69VQ>?	NVG1S4FoOjRiaB?=	NXvYO\|BD\Gm\|coXweJMh\|rOlLXPoZYlvKGO7dH;rbY5mKHOrZ37hcIlv\w>?	NVHqNVhNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGzPFMzPDFpPkKxN\|g{OjRzPD;hQi=>
CD4+ T	NUnMWpp4TnWwY4Tpc44hSXO\|YYm=	NHrBXokyODBibl2=	MYmyOE81QCCq	NWrMVIt5[WK{b3fheIV{KEOGMz3pcoR2[2WmIIDoc5NxcG:{eXzheIlwdiCxZjDTWGFVew>?	M17QO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOEi0OVgxLz5{MUi4OFU5ODxxYU6=
CD4+ T	NHHHZ2FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M{i3TVExOC93MECgcm0>	NFP1Rmg1QCCq	M{DkdIlvcGmkaYTzJIFvfGlvQ1SzMYlv\HWlZXSgR2Q1M8LiVDDj[YxtKHC{b3zp[oVz[XSrb36=	MmDPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF6OES1PFAoRjJzOEi0OVgxRC:jPh?=
CD4+ T	NY[5SFNDTnWwY4Tpc44hSXO\|YYm=	Mk[wNlAwOTByL{WwNEBvVQ>?	NEjFd2U1QCCq	MnjXbY5pcWKrdIOgeIhmKGyndnXsd{Bw\iBiSVytOEwhUU[QLd8zMEBKVC1zN1GgZY5lKEmOLUKy	NVPkTm0xRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG4PFQ2QDBpPkKxPFg1PThyPD;hQi=>
Sf9	MmLDSpVv[3Srb36gZZN{[Xl?		NXXTZYtnOzBibXnudy=>	MVXJcohq[mm2aX;uJI9nKGi3bXHuJGdUXC2odYPl[EBLSUt\|IHPheIFtgXSrYzDkc41icW5iZYjwdoV{e2WmIHnuJIJi[3Wub4\pdpV{NWmwZnXjeIVlKFOoOTDj[YxteyC3c3nu[{Bxd2y7Z3z1eIFucWNiYXPp[E11gXKxc3nu[UBieyC\|dXLzeJJifGViYX\0[ZIhOzBibXnud{BjgSCHTFnTRUwhU2liPTCwMlAxODRizszNMi=>	NXj5bplCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO2Olg1QDRpPkKzOlY5PDh2PD;hQi=>
Sf9	NHuyOm5HfW6ldHnvckBie3OjeR?=		NILOTVk6OCCvaX7z	NWj3b5dWUW6qaXLpeIlwdiCxZjDoeY1idiC{ZXPvcYJqdmGwdDDOMZRmem2rbnHsJGdUXC22YXfn[YQhUkGNMzDlfJBz\XO\|ZXSgbY4hW2Z7IHPlcIx{KHW\|aX7nJGJqd3Srbj3MR{1GWUWGRWDFS2R[TkWZTFWgZZMhe3Wkc4TyZZRmKGGodHXyJFkxKG2rboOgZpkhXFJvRmLFWEBie3OjeTygTWM2OCB;IECuNFAxPiEQvF2u	M1r6RVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MEi3O\|UxLz5{MkC4O\|c2ODxxYU6=
Sf9	MUnGeY5kfGmxbjDhd5NigQ>?		M4[xOlMxKG2rboO=	M4DlXmlvcGmkaYTpc44hd2ZiaIXtZY4hT1OWLX\1d4VlKEqDS{GgZ4F1[Wy7dHnjJIRwdWGrbjDlfJBz\XO\|ZXSgbY4h[mGldXzveolzfXNvaX7m[YN1\WRiU3[5JINmdGy\|IIXzbY5oKHCxbInncJV1[W2rYzDhZ4llNXS7cn;zbY5mKGG\|IIP1ZpN1emG2ZTDh[pRmeiB\|MDDtbY5{KGK7IFXMTXNCNCCNaTC9JFAvODByNzFOwG0v	NV;MRW56RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO2Olg1QDRpPkKzOlY5PDh2PD;hQi=>
Sf9	MYrGeY5kfGmxbjDhd5NigQ>?		NIjpWok{OCCvaX7z	NF7uUpRKdmirYnn0bY9vKG:oIHj1cYFvKEeVVD3meZNm\CCMQVuyJINifGGueYTpZ{Bld22jaX6g[ZhxemW\|c3XkJIlvKGKjY4Xsc5ZqenW\|LXnu[oVkfGWmIGPmPUBk\WyuczD1d4lv\yCyb3z5[4x2fGGvaXOgZYNq\C22eYLvd4lv\SCjczDzeYJ{fHKjdHWgZYZ1\XJiM{CgcYlveyCkeTDFUGlUSSxiS3mgQUAxNjByMEeg{txONg>?	MlXIQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN4Nki0PFQoRjJ\|Nk[4OFg1RC:jPh?=
Sf9	MUXGeY5kfGmxbjDhd5NigQ>?			NGXHbJBKdmirYnn0bY9vKG:oIHj1cYFvKHKnY3;tZolv[W62IFfTWE11[WepZXSgTmgyKGSxbXHpckApPzh3IITvNVEzPSlib3[gTmFMOyCneIDy[ZN{\WRiaX6gbY5{\WO2IGPmPUBk\WyuczDifUBGVEmVQTygTWM2OCB;IECuNFAyKM7:TT6=	MkjtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTR3OUOxPFIoRjF2NUmzNVgzRC:jPh?=
Sf9	MX\GeY5kfGmxbjDhd5NigQ>?			M3Tz[mlvcGmkaYTpc44hd2ZiR2PUMZRi\2enZDDoeY1idiCMQVuzJINifGGueYTpZ{Bld22jaX6g[ZhxemW\|c3XkJIlvKFOoOTDj[YxteyCkeTDFUGlUSSxiSVO1NEA:KDBwMECxJO69VS5?	M4HzdVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUC1O\|EyLz5{MUGwOVcyOTxxYU6=
Sf9	NYTDWFRbTnWwY4Tpc44h[XO\|YYm=		MXm5NEBucW6\|	MUfJcohq[mm2aX;uJI9nKGi3bXHuJJJm[2:vYnnuZY51KE5vdHXycYlv[WxiR2PUMZRi\2enZDDKRWsyKGW6cILld5Nm\CCrbjDT[lkh[2WubIOgeZNqdmdiQnnveIlvNUyFLVXRSWRGWEWJRGnGSXdNTSCjczDzeYJ{fHKjdHWgZYZ1\XJiOUCgcYlveyCkeTDUVk1HWkWWIHHzd4F6NCCLQ{WwJF0hOC5yMEOg{txONg>?	Ml;EQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJyOEe3OVAoRjJ{MEi3O\|UxRC:jPh?=
Sf9	MkDSSpVv[3Srb36gZZN{[Xl?			M1jaXmlvcGmkaYTpc44hd2ZiR2PUMZRi\2enZDDoeY1idiCMQVuzJINifGGueYTpZ{Bld22jaX6g[ZhxemW\|c3XkJIlvKFOoOTDj[YxteyCkeTDFUGlUSSxiSVO1NEA:KDBwMECzN{DPxE1w	NGXYN2Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUGwOVcyOSd-MkGxNFU4OTF:L3G+
Sf9	NXvJVmRWTnWwY4Tpc44h[XO\|YYm=		M1rwNFkxKG2rboO=	MonaTY5pcWKrdHnvckBw\iCqdX3hckBz\WOxbXLpcoFvfCCQLYTldo1qdmGuIFfTWE11[WepZXSgTmFMOiCneIDy[ZN{\WRiaX6gV4Y6KGOnbHzzJJV{cW6pIFLpc5Rqdi2OQz3FVWVFTVCHR1TZSmVYVEViYYOgd5Vje3S{YYTlJIFnfGW{IEmwJI1qdnNiYomgWHIuTlKHVDDhd5NigSxiSVO1NEA:KDBwMEC0JO69VS5?	Mn2xQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJyOEe3OVAoRjJ{MEi3O\|UxRC:jPh?=
SF21	NXfWdJFzTnWwY4Tpc44h[XO\|YYm=		M4PvR\|ExKG2rboO=	NFXy[ZRKdmirYnn0bY9vKG:oIFrBT\|IhMHWwa37ve44hd3KrZ3nuLUBmgHC{ZYPz[YQhcW5iU1[yNUBk\WyuczD1d4lv\yCEaX;0bY4uU0GLRWTET2V[YVSYS1SgZZMhe3Wkc4TyZZRmKGGwZDDbN\|NR\2GvbXHdRXRRKGmwY4XiZZRm\CCob4KgNVAhdWmwczDwdolweiC2bzDzeYJ{fHKjdHWgZYRlcXSrb36gcYVie3W{ZXSgZYZ1\XJiM{CgcYlveyCkeTDUc5Bkd3WwdDDhcoFtgXOrczygTWM2OCB;IECuNFA1KM7:TT6=	MWq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzV2MU[3NEc,OjN3NEG2O\|A9N2F-
insect cells	NG\2cGtHfW6ldHnvckBie3OjeR?=			NIi2OXlKdmirYnn0bY9vKG:oIFfTWE11[WepZXSgToFsOSCneIDy[ZN{\WRiaX6gbY5{\WO2IHPlcIx{KHW\|aX7nJFcxKHWPIFHUVEwhUUN3MDC9JFAvODB4MTFOwG0v	NYi4TFFCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkGxOVU3ODVpPkKxNVU2PjB3PD;hQi=>
insect cells	MUfGeY5kfGmxbjDhd5NigQ>?			MUjJcohq[mm2aX;uJI9nKEeVVD30ZYdo\WRiSnHrN{BmgHC{ZYPz[YQhcW5iaX7z[YN1KGOnbHzzJJV{cW6pIEG4JJVOKEGWUDygTWM2OCB;IECuNFA5KM7:TT6=	MUG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF3NU[wOUc,OjFzNUW2NFU9N2F-
T-cells	MnTESpVv[3Srb36gZZN{[Xl?		MYm3NkBpenN?	NGryNHpKdmirYnn0bY9vKG:oIFnMNk1qdmS3Y3XkJJBzd2yrZnXyZZRqd25ib3[gbJVu[W5iVDDj[YxteyCjc4Pld5Nm\CCjczDbN2hefGi7bXnkbY5mKGmwY3;ydI9z[XSrb36gZYZ1\XJiN{KgbJJ{KGK7IIPjbY51cWyuYYTpc44h[2:3boTpcoctKEmFNUCgQUAxNjBzMTFOwG0v	MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPDV7M{G4Nkc,OTR3OUOxPFI9N2F-
insect cells	MkPFSpVv[3Srb36gZZN{[Xl?			NGn2TJNKdmirYnn0bY9vKG:oIFfTWE11[WepZXSgToFsOiCneIDy[ZN{\WRiaX6gbY5{\WO2IHPlcIx{KHW\|aX7nJFIxKHWPIFHUVEwhUUN3MDC9JFAvODF{IN88UU4>	M2HzRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzMUW1OlA2Lz5{MUG1OVYxPTxxYU6=
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Ba/F3	MnXqSpVv[3Srb36gZZN{[Xl?		NYTJN2dRPjBibXnudy=>	MlnHTY5pcWKrdHnvckBw\iCWRVyt[pV{\WRiSlHLNUBmgHC{ZYPz[YQhcW5iQnGvSlMh[2WubIOgZZN{\XO\|ZXSgZZMhcW6qaXLpeIlwdiCxZjDTWGFVPSCyaH;zdIhwenmuYYTpc44h[W[2ZYKgOlAhdWmwczDifUBCdHCqYWPjdoVmdiCjc4PhfUwhUUN3MDC9JFAvODJ4IN88UU4>	NEfKT2Q9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkC4O\|c2OCd-MkKwPFc4PTB:L3G+
T-cells	MXjGeY5kfGmxbjDhd5NigQ>?			NF2wemdKdmirYnn0bY9vKG:oIFrBT\|MwOSCrbjDoeY1idiCWIHPlcIx{KGW6cILld5NqdmdiQ1SzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gTWwzNXO2aX31cIF1\WRiU2TBWFViKHCqb4PwbI9zgWyjdHnvckwhUUN3MDC9JFAvODJ6IN88UU4>	M3LtcVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NUSwOlQ5Lz5{M{W0NFY1QDxxYU6=
PBMC	NYj4XVVYTnWwY4Tpc44h[XO\|YYm=			NYm5UXh2UW6qaXLpeIlwdiCLTD23MYlv\GO3ZXSgV3RCXDVicHjvd5Bpd3K7bHH0bY9vKGmwIHj1cYFvKFCETVOgZ4VtdHNiYomg[oxwfyCleYTvcYV1enluIFnDOVAhRSByLkCzPUDPxE1w	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjl{N{SyN{c,OjZ7Mke0NlM9N2F-
TF1	NUjXNYRMTnWwY4Tpc44h[XO\|YYm=		MmXINlAhdWmwcx?=	MmDLTY5pcWKrdHnvckBw\iCMQVuxJIlvKGi3bXHuJHRHOSClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGlNPi2rbnT1Z4VlKFOWQWSzJJBpd3OyaH;yfYxifGmxbjDpcoN2[mG2ZXSg[o9zKDJyIH3pcpMh\m:ubH;3[YQh[nliSVy2JINp[WyuZX7n[UBnd3JiM{CgcYlveyCrbjDwdoV{\W6lZTDv[kB4cG:uZTDicI9w\CxiRVO1NEA:KDBwMESzJO69VS5?	NWjpUGdDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO2OVkzOTRpPkKzOlU6OjF2PD;hQi=>
TF1	NULvNmxtTnWwY4Tpc44h[XO\|YYm=			MoPDTY5pcWKrdHnvckBw\iCMQVuxJIlvKGi3bXHuJHRHOSClZXzsd{Bie3Onc4Pl[EBieyC\|dYDwdoV{e2mxbjDv[kBKVDZvc4TpcZVt[XSnZDDTWGFVOyCyaH;zdIhwenmuYYTpc44h[nliQXzwbIFU[3KnZX6gZZN{[XluIFnOTEA:KDBwMES1JO69VS5?	NUO3RY5QRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[zO\|I3PTNpPkK2N\|czPjV\|PD;hQi=>
CTLL	MnPDSpVv[3Srb36gZZN{[Xl?			NILRcJhKdmirYnn0bY9vKG:oIFrhb\|MudWWmaXH0[YQhUUx{LXnu[JVk\WRiU4TheFUheGixc4Doc5J6dGG2aX;uJIlvKG2xdYPlJGNVVExiY3XscJMh[nliY3XscE1j[XOnZDDhd5NigSxiSVO1NEA:KDBwMES4JO69VS5?	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTF3NU[wOUc,OjFzNUW2NFU9N2F-
Sf9	MkP4SpVv[3Srb36gZZN{[Xl?		NHjkSnc6OCCvaX7z	MkPDTY5pcWKrdHnvckBw\iCqdX3hckBz\WOxbXLpcoFvfCCQLYTldo1qdmGuIFfTWE11[WepZXSgWHlMOiCneIDy[ZN{\WRiaX6gV4Y6KGOnbHzzJJV{cW6pIFLpc5Rqdi2OQz3FVWVFTVCHR1TZSmVYVEViYYOgd5Vje3S{YYTlJIFnfGW{IEmwJI1qdnNiYomgWHIuTlKHVDDhd5NigSxiSVO1NEA:KDBwMEWyJO69VS5?	MkTsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJyOEe3OVAoRjJ{MEi3O\|UxRC:jPh?=
TF1	MXjGeY5kfGmxbjDhd5NigQ>?			MkOwTY5pcWKrdHnvckBw\iCMQVuxJIlvKGi3bXHuJHRHOSClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGlNOi2rbnT1Z4VlKFOWQWSzJJBpd3OyaH;yfYxifGmxbjygSWM2OCB;IECuNFU{KM7:TT6=	MmDiQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ3OUG0NFIoRjJ{NUmxOFAzRC:jPh?=
TF1	NGS0XXdHfW6ldHnvckBie3OjeR?=		NYXCdJlVOjBibXnudy=>	MXzJcohq[mm2aX;uJI9nKEqDS{GgbY4hcHWvYX6gWGYyKGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gTWw3NWmwZIXj[YQhW1SDVEOgdIhwe3Cqb4L5cIF1cW:wIHnuZ5Vj[XSnZDDmc5IhOjBibXnud{BxemmxcjD0c{BKVDZvaX7keYN1cW:wIH3lZZN2emWmIHHmeIVzKDNyIITvJFQ2KG2rboOsJGVEPTBiPTCwMlA2OyEQvF2u	M3rIO\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{Nkm4NFg1Lz5{Mk[5PFA5PDxxYU6=
TF1	NUTWVmJOTnWwY4Tpc44h[XO\|YYm=		NGn6R2IzOCCvaX7z	NXfjOphEUW6qaXLpeIlwdiCxZjDKRWsyKGmwIHj1cYFvKFSIMTDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKEmONj3pcoR2[2WmIGPURXQ{KHCqb4PwbI9zgWyjdHnvckBqdmO3YnH0[YQh\m:{IEKwJI1qdnNiZn;scI94\WRiYomgTWw3KGOqYXzs[Y5o\SCob4KgN\|AhdWmwczygSWM2OCB;IECuNFU{KM7:TT6=	NXzqSW5mRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO2OVkzOTRpPkKzOlU6OjF2PD;hQi=>
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T-cells	NVraNmhETnWwY4Tpc44h[XO\|YYm=			NF\4OJZKdmirYnn0bY9vKG:oIHHscI9o\W6rYzDj[Yxtey2\|dHnteYxifGWmIIDyc4xq\mW{YYTpc44hcW5ibX;ub4V6KFRiY3XscJMh[nlibXn4[YQhdHmvcHjvZ5l1\SC{ZXHjeIlwdiCvZYToc4QtKEmFNUCgQUAxNjB3NzFOwG0v	Mkf5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTR3OUOxPFIoRjF2NUmzNVgzRC:jPh?=
CD34+	NIK5fG1HfW6ldHnvckBie3OjeR?=			NXTMXpd[UW6qaXLpeIlwdiCxZjDKRWszKGmwIHj1cYFvKEOGM{SrJINmdGy\|IHHzd4V{e2WmIHHzJIlvcGmkaYTpc44hd2ZiRWDPMY1m\GmjdHXkJINmdGxicILvcIln\XKjdHnvckwhUUN3MDC9JFAvODdzIN88UU4>	M2fjbVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4OUK3OFI{Lz5{NkmyO\|QzOzxxYU6=
TF1	MlfuSpVv[3Srb36gZZN{[Xl?			MlvUTY5pcWKrdHnvckBw\iCLTEStbY5lfWOnZDDwdo9tcW[ncnH0bY9vKG:oIGTGNUBk\WyuczygTWM2OCB;IECuNFgh\|ryPLh?=	M{PkT\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF4OUO0OFU4Lz5zNkmzOFQ2PzxxYU6=
T-cells	MXLGeY5kfGmxbjDhd5NigQ>?			MYDJcohq[mm2aX;uJI9nKGGubH;n[Y5q[yClZXzsd{1{fGmvdXzheIVlKHC{b3zp[oVz[XSrb36gbY4hcHWvYX6gWEBk\WyuczDifUBucXinZDDsfY1xcG:leYTlJJJm[WO2aX;uJI1mfGixZDygTWM2OCB;IECuNFg4KM7:TT6=	Ml;jQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTR3OUOxPFIoRjF2NUmzNVgzRC:jPh?=
TF1	M4PZSWZ2dmO2aX;uJIF{e2G7		M{X4XlIxKG2rboO=	NGfMSGxKdmirYnn0bY9vKG:oIFrBT\|IhcW5iaIXtZY4hXEZzIHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhTVCRLXnu[JVk\WRiU2TBWFUheGixc4Doc5J6dGG2aX;uJIlv[3WkYYTl[EBnd3JiMkCgcYlveyCycnnvdkB1dyCHUF:tbY5lfWO2aX;uJI1m[XO3cnXkJIFnfGW{IEOwJJRwKDR3IH3pcpMtKEWFNUCgQUAxNjB7MzFOwG0v	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjZ7OEC4OEc,OjJ4OUiwPFQ9N2F-
TF1	MofqSpVv[3Srb36gZZN{[Xl?		NXLPPFJFOjBibXnudy=>	NEn1d3JKdmirYnn0bY9vKG:oIFrBT\|IhcW5iaIXtZY4hXEZzIHPlcIx{KGG\|c3Xzd4VlKGG\|IHnubIljcXSrb36gc4YhTVCRLXnu[JVk\WRiU2TBWFUheGixc4Doc5J6dGG2aX;uJIlv[3WkYYTl[EBnd3JiMkCgcYlveyCob3zsc5dm\CCkeTDJUFYh[2ijbHzlcodmKG[xcjCzNEBucW6\|LDDFR\|UxKD1iMD6wPVMh\|ryPLh?=	M2\2PVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ\|NkW5NlE1Lz5{M{[1PVIyPDxxYU6=
PBMC	MkPBSpVv[3Srb36gZZN{[Xl?			NIf1VJZKdmirYnn0bY9vKG:oIFrBT\|EhcW5iaIXtZY4hWEKPQzDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKEmOLU[tbY5lfWOnZDDNR3AyKHOnY4LleIlwdixiSVO1NEA:KDBwMEm1JO69VS5?	MkTnQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ7Mke0NlMoRjJ4OUK3OFI{RC:jPh?=
TF1	NETBbJdHfW6ldHnvckBie3OjeR?=		Mm\SNkBpenN?	M3HaZ2lvcGmkaYTpc44hd2ZiSlHLNkBqdiCJTVPTSk1{fGmvdXzheIVlKGi3bXHuJHRHOSClZXzsd{Bie3Onc4Pl[EBieyC\|dYDwdoV{e2mxbjDv[kBUXEGWNTDwbI9{eGixconsZZRqd25icILlbY5kfWKjdHXkJIZweiB{IHjyd{Bnd2yub4fl[EBjgSCJTVPTSkB{fGmvdXzheIlwdiCob4KgOVAhdWmwczDifUBHSUOVIILlZYRmeiCjbnHsfZNqeyxiSVO1NEA:KDBwMEm1JO69VS5?	MlrjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjdzM{CzOVkoRjJ5MUOwN\|U6RC:jPh?=
TF1	Mn;sSpVv[3Srb36gZZN{[Xl?			NGC4NmNKdmirYnn0bY9vKG:oIFrBT\|IhcW5iRWDPMZN1cW23bHH0[YQhcHWvYX6gWGYyKGOnbHzzJIV5eHKnc4Ppcoche3SjYnz5JIlvfGWpcnH0[YQh[mW2YT3sZYN1[W2jc3WgdoVxd3K2ZYKg[4Vv\SC3bnTldkBkd262cn;sJI9nKFOWQWS1JJJme3CxboPlJIVt\W2nboTzJIlvKGmwdHXy[oVzd25icnXneYxifG:{eTDmZYN1d3JiMTDn[Y5mKHC{b33veIVzKGK7IH\seY9z\XOlZX7j[UBie3OjeTygTWM2OCB;IECuNVA4KM7:TT6=	NYnWV2JpRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkmxOVYyOzZpPkK5NVU3OTN4PD;hQi=>
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T-cells	NFryZWRHfW6ldHnvckBie3OjeR?=			NHnEUGZKdmirYnn0bY9vKG:oIHHscI9o\W6rYzDj[Yxtey2\|dHnteYxifGWmIIDyc4xq\mW{YYTpc44hcW5ibX;1d4UhXCClZXzsd{BjgSCvaYjl[EBtgW2yaH;jfZRmKHKnYXP0bY9vKG2ndHjv[EwhUUN3MDC9JFAvOTF3IN88UU4>	MUK8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPDV7M{G4Nkc,OTR3OUOxPFI9N2F-
ME180	MojpSpVv[3Srb36gZZN{[Xl?			Mlv0TY5pcWKrdHnvckBw\iCMQVuxJIlvKEmONj3zeIlufWyjdHXkJIh2dWGwIF3FNVgxKGOnbHzzJIV5eHKnc4Ppcoche3SjYnz5JIlvfGWpcnH0[YQh[mW2YT3sZYN1[W2jc3WgdoVxd3K2ZYKg[4Vv\SC3bnTldkBkd262cn;sJI9nKHOrcz3pcoR2[2mkbHWg[YxmdWWwdDDifUBndHWxcnXzZ4Vv[2ViYYPzZZktKEmFNUCgQUAxNjF{NDFOwG0v	M1LYWFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7MUW2NVM3Lz5{OUG1OlE{PjxxYU6=
CTLL-2	MVPBcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		MlmyO\|IhcHK\|	NU\UTpo3SW62aYDyc4xq\mW{YYTpeoUh[WO2aY\peJkh[WejaX7zeEBKVC1{LYP0bY12dGG2ZXSgcY92e2ViQ2TMUE0zKGOnbHzzJIV5eHKnc4PpcochUkGNMT;KRWs{KGGodHXyJFczKGi{czDifUBidGGvYYKgZox2\SCjc4PhfUwhUUN3MDC9JFAvOTN{IN88UU4>	MWS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQTd4MkKzPEc,OTl5NkKyN\|g9N2F-
HT2	M1XkOmZ2dmO2aX;uJIF{e2G7			NV31S4dXUW6qaXLpeIlwdiCxZjDKRWs{KGmwIH3veZNmKEiWMjDj[YxteyCjc4Pld5Nm\CCjczDzeZBxemW\|c3nvckBw\iClZXzsJIdzd3e2aDygTWM2OCB;IECuNVU3KM7:TT6=	NXHNUG9CRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMke3O\|EyQDBpPkK3O\|cyOThyPD;hQi=>
DND/L12	NH:3dWdHfW6ldHnvckBie3OjeR?=		MVGzNEBucW6\|	M4rncmlvcGmkaYTpc44hd2ZiSlHLN{BqdiCqdX3hckBFVkRxTEGyJINmdGy\|IHHmeIVzKDNyIH3pcpMh[nlibIXjbYZmemG\|ZTDhd5NigSCrbjDwdoV{\W6lZTDv[kBpfW2jbjDz[ZJ2dSCjbHL1cYlvNCCLQ{mwJF0hOC5zNjFOwG0v	NYnCc41VRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUS1PVMyQDJpPkG0OVk{OTh{PD;hQi=>
T-cells	Ml3USpVv[3Srb36gZZN{[Xl?			Ml2zTY5pcWKrdHnvckBw\iCMQVuyM\|EhcW5iaIXtZY4hXCClZXzsd{BmgHC{ZYPzbY5oKEOGMzDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIFnGUodidW2jLYP0bY12dGG2ZXSgV3RCXDFicHjvd5Bpd3K7bHH0bY9vNCCLQ{WwJF0hOC5zNzFOwG0v	MoS0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN3NEC2OFgoRjJ\|NUSwOlQ5RC:jPh?=
insect	NVmzXmtnTnWwY4Tpc44h[XO\|YYm=			MoDsTY5pcWKrdHnvckBw\iCJU2SteIFo\2WmIGT5b\|Ih\XiycnXzd4VlKGmwIHnud4VkfCClZXzsd{B2e2mwZzCzOUB2VSCDVGCsJGlEPTBiPTCwMlE4PiEQvF2u	NH32ZYg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUG1OVYxPSd-MkGxOVU3ODV:L3G+
Ba/F3	M{jXeWZ2dmO2aX;uJIF{e2G7		MlW2OlAhdWmwcx?=	M{f3emlvcGmkaYTpc44hd2ZiVFXMMYZ2e2WmIFrBT\|Ih\XiycnXzd4VlKGmwIFLhM2Y{KGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gV3RCXDVicHjvd5Bpd3K7bHH0bY9vKGGodHXyJFYxKG2rboOgZpkhSWyyaHHTZ5Jm\W5iYYPzZZktKEmFNUCgQUAxNjJ4NTFOwG0v	NXuyTmdkRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKwPFc4PTBpPkKyNFg4PzVyPD;hQi=>
TF1	M1zndGZ2dmO2aX;uJIF{e2G7			MYXJcohq[mm2aX;uJI9nKEqDS{KgbY4hcHWvYX6gWGYyKGOnbHzzJIF{e2W\|c3XkJIF{KHO3cIDy[ZN{cW:wIH;mJINmdGxiZ4Lve5RpNCCLQ{WwJF0hOC5{N{WxJO69VS5?	M2TKeVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ5N{exNVgxLz5{N{e3NVE5ODxxYU6=
CD34+	M2nhNmZ2dmO2aX;uJIF{e2G7			M3LMS2lvcGmkaYTpc44hd2ZiSlHLNkBpd22xZHnt[ZIhcW5iaIXtZY4hS0R\|NDugZ4VtdHNic4Dpb4VlKGmwdH:gbJVu[W5id3jvcIUh[myxb3SgZZN{\XO\|ZXSgZZMhcW6qaXLpeIlwdiCxZjDFVG8ucW6mdXPl[EBUXEGWLUWgdIhwe3Cqb4L5cIF1cW:wIIDy[Ylv[3WkYYTl[EBnd3JiNEWgcYlveyCob3zsc5dm\CCkeTDFVG8h[WSmaYTpc44hdWWjc4Xy[YQh[W[2ZYKgNVUhdWmwczDifUBHSUOVIHHuZYx6e2m\|LDDJR\|UxKD1iMD6zNFIh\|ryPLh?=	MXG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDRzN{WzN{c,OjR2MUe1N\|M9N2F-
HUO3	NGPPS3JHfW6ldHnvckBie3OjeR?=		MWK0JIRigXN?	M3;vNmlvcGmkaYTpc44hd2ZiaIXtZY4hT01vQ2PGMYlv\HWlZXSgdJJwdGmoZYLheIlwdiCrbjDoeY1idiCKVV:zJINmdGy\|IHHzd4V{e2WmIHHzJHs{UF22aIntbYRqdmViaX7jc5Jxd3KjdHnvckBi\nSncjC0JIRigXNiYomgd4NqdnSrbHzheIlwdiClb4XueIlv\yxiSVO1NEA:KDBwM{K0JO69VS5?	M37ycFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF2NUmzNVgzLz5zNEW5N\|E5OjxxYU6=
HU03	NUHEeo1KTnWwY4Tpc44h[XO\|YYm=		Mn;XO\|IhcHK\|	NWq0WYFmUW6qaXLpeIlwdiCxZjDHUU1EW0ZvaX7keYNm\CCqdX3hckBJXTB\|IHPlcIx{KHC{b3zp[oVz[XSrb36gZYZ1\XJiN{KgbJJ{KGK7IGuzTH11cHmvaXTpcoUhcW6lb4Lwc5JifGmxbjDhd5NigSxiSVO1NEA:KDBwM{K0JO69VS5?	MmnzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjFzMEW3NVEoRjJzMUC1O\|EyRC:jPh?=
BAF3	NEfPU5JCdnSrcILvcIln\XKjdHn2[UBie3OjeR?=		NW\ZeJpnPzJiaILz	M3rKcWFvfGmycn;sbYZmemG2aY\lJIFkfGm4aYT5JIFo[Wmwc4SgcY92e2ViQlHGN{Bk\WyuczDlfJBz\XO\|aX7nJHRGVC2MQVuzJItqdmG\|ZTDh[pRmeiB5MjDodpMh[nliYXzhcYFzKGKudXWgZZN{[XluIFnDOVAhRSByLkW3JO69VS5?	NH7OeI89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUe2NlI{QCd-MUm3OlIzOzh:L3G+
T-cells	M1S0UGZ2dmO2aX;uJIF{e2G7		MnvMN{Bl[Xm\|	M4C1O2lvcGmkaYTpc44hd2ZiY3XscEBxem:uaX\ldoF1cW:wIH;mJGlNOi2jY4TpeoF1\WRiYX7kJGNFOyCjbnSgR2QzQCCjboTpZo9lgS2\|dHnteYxifGWmIH3veZNmKEOGND3wc5NqfGm4ZTDUJINmdGy\|IHHmeIVzKDNiZHH5d{BjgSC[VGSgZZN{[XluIFnDOVAhRSByLk[zJO69VS5?	M2r0WFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzNyNE[wPFQzLz5\|MES2NFg1OjxxYU6=
NK92	M1G3[2Z2dmO2aX;uJIF{e2G7		NUfxZVg{OjBibXnudy=>	MV7Jcohq[mm2aX;uJI9nKFS\S{KgbY4hcHWvYX6gUms6OiClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGlNOTJvaX7keYNm\CCVVFHUOEBxcG:\|cHjvdplt[XSrb36gbY5kfWKjdHXkJIZweiB{MDDtbY5{KG[xbHzve4VlKGK7IFnMNVIh[2ijbHzlcodmKG[xcjC0OUBucW6\|LDDFR\|UxKD1iMD63NUDPxE1w	NYK4W3hMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO2OVkzOTRpPkKzOlU6OjF2PD;hQi=>
TF1	M1XuRWZ2dmO2aX;uJIF{e2G7			NUnRSW5jUW6qaXLpeIlwdiCxZjDJUFMucW6mdXPl[EBxem:uaX\ldoF1cW:wIH;mJHRHOSClZXzsd{whUUN3MDC9JFAvQCEQvF2u	M4DNV\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF4OUO0OFU4Lz5zNkmzOFQ2PzxxYU6=
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Ba/F3	NEnadWVHfW6ldHnvckBie3OjeR?=		MYK2NEBucW6\|	MVfJcohq[mm2aX;uJI9nKFSHTD3meZNm\CCWWVuyJIV5eHKnc4Pl[EBqdiCEYT;GN{Bk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIGPURXQ2KHCqb4PwbI9zgWyjdHnvckBi\nSncjC2NEBucW6\|IHL5JGFteGijU3Py[YVvKGG\|c3H5MEBKSzVyIE2gNU4zKM7:TT6=	M2X3fVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MEi3O\|UxLz5{MkC4O\|c2ODxxYU6=
T-cells	MXrGeY5kfGmxbjDhd5NigQ>?		M1nYWlczKGi{cx?=	NWXDRVBoUW6qaXLpeIlwdiCxZjDKRWs{KGmwIILheEB{eGynbn;jfZRq[yCWIHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDpckBKVC1{LXnu[JVk\WRiY3XscEBxem:uaX\ldoF1cW:wIHHmeIVzKDd{IHjyd{BjgSCPVGOgZZN{[XluIFnDOVAhRSBzLkKg{txONg>?	NFLOb2s9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9\|MEGzPVU4PSd-M{CxN\|k2PzV:L3G+
SZ4	MWDGeY5kfGmxbjDhd5NigQ>?			M1j6VGlvcGmkaYTpc44hd2ZiSlHLN{BqdiCqdX3hckBUYjRiY3XscJMh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJGlNOi2\|dHnteYxifGWmIGPURXQ2KHCqb4PwbI9zgWyjdHnvckBxemWrbnP1ZoF1\WRiZn;yJFEhcHJiZn;scI94\WRiYomgTWwzKHO2aX31cIF1cW:wIHHu[EBu\WG\|dYLl[EBi\nSncjCxOUBucW6\|IHL5JG1UTCCjc4PhfUwhUUN3MDC9JFEvOjFizszNMi=>	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8{ODR4MEi0Nkc,OzB2NkC4OFI9N2F-
BAF3	MX7BcpRqeHKxbHnm[ZJifGm4ZTDhd5NigQ>?		MWK3NkBpenN?	NHnXNFVCdnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JI1wfXOnIFLBSlMh[2WubIOg[ZhxemW\|c3nu[{BVTUxvSlHLNkBscW6jc3WgZYZ1\XJiN{KgbJJ{KGK7IHHsZY1ieiCkbIXlJIF{e2G7LDDJR\|UxKD1iMT61O\|Qh\|ryPLh?=	NUHwTHVMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUm3OlIzOzhpPkG5O\|YzOjN6PD;hQi=>
HEL	M3GxO2Z2dmO2aX;uJIF{e2G7		NIrtVHIyKGi{	Mn[2TY5pcWKrdHnvckBw\iCMQVuyJHY3OTeIIH31eIFvfCCrbjDoeY1idiCKRVygZ4VtdHNiYX\0[ZIhOSCqcjygTWM2OCB;IESuO\|I1KM7:TT6=	NF3HcnE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{e3NVE5OCd-Mke3O\|EyQDB:L3G+
Jurkat	MXzGeY5kfGmxbjDhd5NigQ>?		NV3vVYd2OjRiaILz	MVHJcohq[mm2aX;uJI9nKGGwdHmtR2Q{N2GwdHmtR2QzQC2rbnT1Z4VlKEmOMjDwdo9lfWO2aX;uJIlvKGi3bXHuJGp2emujdDDj[YxteyCjZoTldkAzPCCqcoOgZpkhe2OrboTpcIxifGmxbjDjc5VvfGmwZzygTWM2OCB;IEeuPFQh\|ryPLh?=	NFfEbXA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNEW5N\|E5Oid-MUS1PVMyQDJ:L3G+
YT	NFLiToVHfW6ldHnvckBie3OjeR?=	NVzqNXRCOzBibnevcYw>		NWfLc2xjUW6qaXLpeIlwdiCxZjDJUFIucW6mdXPl[EBLSUt\|IIDoc5NxcG:{eXzheIlwdiCrbjDoeY1idiC\VDDj[YxteyCjdDCzNEBv\y:vbDDifUBqdW23bn;icI91fGmwZzDhcoFtgXOrcx?=	MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPDV7M{G4Nkc,OTR3OUOxPFI9N2F-
YT	NXW0VoV5TnWwY4Tpc44h[XO\|YYm=	NILQOZY{OCCwZz;tcC=>		M{fuR2lvcGmkaYTpc44hd2ZiSVyyMYlv\HWlZXSgV3RCXDWDIIDoc5NxcG:{eXzheIlwdiCrbjDoeY1idiC\VDDj[YxteyCjdDCzNEBv\y:vbDDifUBqdW23bn;icI91fGmwZzDhcoFtgXOrcx?=	M{X1[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF2NUmzNVgzLz5zNEW5N\|E5OjxxYU6=
YT	MkjSSpVv[3Srb36gZZN{[Xl?	M1zmVFMxKG6pL33s		MnPhTY5pcWKrdHnvckBw\iCLTEKtbY5lfWOnZDDTWGFVPUJicHjvd5Bpd3K7bHH0bY9vKGmwIHj1cYFvKFmWIHPlcIx{KGG2IEOwJI5oN22uIHL5JIludXWwb3Lsc5R1cW6pIHHuZYx6e2m\|	NF;uZnQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNEW5N\|E5Oid-MUS1PVMyQDJ:L3G+
NK-cells	NHvzVndKdW23bn;zeZBxemW\|c3n2[UBie3OjeR?=	NYn3eI5uOSC2bzC1JI1oN2up	NHPTXGQ1KHenZXvz	M1SwdmludXWwb4P1dJBz\XO\|aY\lJIFkfGm4aYT5JIlvKG6jaY\lJIN6dm:vb3zneZMhdW:wa3X5JIF{e2W\|c3XkJIF{KGWoZnXjeEBwdiCFREOtR2QyPitiTlugZ4VtdHNiYYSgNUB1dyB3IH3nM4toNCCybzDmc5IhPCC5ZXXrdy=>	NGnsc\|Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zNEW5N\|E5Oid-MUS1PVMyQDJ:L3G+
T-cells	MVLGeY5kfGmxbjDhd5NigQ>?	NVzPbmcxPSC2bzC1NFAhdk1?	MnLTNUBpeg>?	M3:wOWlvcGmkaYTpc44hd2ZiSVyyMYlv\HWlZXSgV5RifDVicHjvd5Bpd3K7bHH0bY9vKGmwIHj1cYFvKEOGNDugWEBk\WyuczDheEA2KHSxIEWwNEBvVSCjZoTldkAyKGi{IHL5JHdme3Sncn6gZoxwfA>?	M3HTe\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF7MEWzO\|U3Lz5zOUC1N\|c2PjxxYU6=
SUM149PT	NV7sNpI4TnWwY4Tpc44h[XO\|YYm=	NVHRWJVvOyC3TR?=	NXvKZmJoOTZiaILz	NVTxSYtRUW6mdXP0bY9vKG:oIGDUVG43KGmwIHj1cYFvKFOXTUG0PXBVKGOnbHzzJIF{e2W\|c3XkJIF{KGmwaHnibZRqd25ib3[gV3RCXDNicHjvd5Bpd3K7bHH0bY9vKGG2IEOgeW0h[W[2ZYKgNVYhcHK\|IHL5JHdme3Sncn6gZoxwfHSrbnegZY5idHm\|aYOgbY4heHKnc3XuZ4Uhd2ZicHXyeoFv[WSjdHW=	MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDl5OEGxNkc,OjR7N{ixNVI9N2F-
Hs578T	M3fpOGZ2dmO2aX;uJIF{e2G7	MY[zJJVO	NEnjZoMyPiCqcoO=	MoW3TY5lfWO2aX;uJI9nKFCWUF62JIlvKGi3bXHuJGh{PTd6VDDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKFOWQWSzJJBpd3OyaH;yfYxifGmxbjDheEA{KHWPIHHmeIVzKDF4IHjyd{BjgSCZZYP0[ZJvKGKub4T0bY5oKGGwYXz5d4l{KGmwIIDy[ZNmdmOnIH;mJJBmen[jbnHkZZRm	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDl5OEGxNkc,OjR7N{ixNVI9N2F-
T-cells	MmPiSpVv[3Srb36gZZN{[Xl?	M3K2[FUxKHSxIEOwNEBvVQ>?	NWrSbpRoOSCqch?=	NUXnWmpjUW6qaXLpeIlwdiCxZjDKRWsyN0qDS{OgbY4hcHWvYX6gR2Q1KHCxc3n0bZZmKFRiY3XscJMh[XO\|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kBKVDRvc4TpcZVt[XSnZDDTWGFVPiCyaH;zdIhwenmuYYTpc44h[XRiNUCgeI8hOzByIH7NJJBz\WmwY4XiZZRm\CCob4KgNUBpeiCob3zsc5dm\CCkeTDJUE01KHO2aX31cIF1cW:wIH3lZZN2emWmIHHmeIVzKDNyIH3pcpMh[nliaX3teY5w[myxdDDhcoFtgXOrcx?=	Mo\kQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl6NUKwOlgoRjJ7OEWyNFY5RC:jPh?=
T-cells	M1zS[mZ2dmO2aX;uJIF{e2G7	NITWU\|g2OCC2bzCzNFAhdk1?	MYixJIhz	NFXOToJKdmirYnn0bY9vKG:oIFrBT\|EwUkGNMzDpckBpfW2jbjDDSFQheG:\|aYTpeoUhXCClZXzsd{Bie3Onc4Pl[EBieyCrbnjpZol1cW:wIH;mJGlNOi2\|dHnteYxifGWmIGPURXQ2KHCqb4PwbI9zgWyjdHnvckBifCCWeYKtOlk2KHKnc3nkeYUh[XRiNUCgeI8hOzByIH7NJJBz\WmwY4XiZZRm\CCob4KgNUBpeiCob3zsc5dm\CCkeTDJUE0zKHO2aX31cIF1cW:wIH3lZZN2emWmIHHmeIVzKDNyIH3pcpMh[nliaX3teY5w[myxdDDhcoFtgXOrcx?=	MkDRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl6NUKwOlgoRjJ7OEWyNFY5RC:jPh?=
T-cells	MWHGeY5kfGmxbjDhd5NigQ>?	MnPtQlMxOCCwTR?=	M1rVO\|EhcHJ?	NUPtVnJPUW6qaXLpeIlwdiCxZjDKRWsyN0qDS{KvWHlMOiCrbjDoeY1idiCFRESgdI9{cXSrdnWgWEBk\WyuczDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIFnMOk1{fGmvdXzheIVlKFOWQWSzJJBpd3OyaH;yfYxifGmxbjDheEA,OzByIH7NJJBz\WmwY4XiZZRm\CCob4KgNUBpeiCob3zsc5dm\CCkeTDJUE03KHO2aX31cIF1cW:wIH3lZZN2emWmIHHmeIVzKDNyIH3pcpMh[nliaX3teY5w[myxdDDhcoFtgXOrcx?=	NVT5e4pFRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm4OVIxPjhpPkK5PFUzODZ6PD;hQi=>
TALL-1	M33Td2Z2dmO2aX;uJIF{e2G7	Mny4NUB2VQ>?	MVSzJIhzew>?	MlfpTY5pcWKrdHnvckBw\iCMQVuzJIlvKGi3bXHuJHRCVExvMTDj[YxteyCjc4Pld5Nm\CCjczDpcohq[mm2aX;uJI9nKEmOLUKgbY5lfWOnZDDTWGFVPSCyaH;zdIhwenmuYYTpc44h[XRiMTD1UUBxemWrbnP1ZoF1\WRiZn;yJFMhcHK\|IH\vcIxwf2WmIHL5JGlNNTJiaX7keYN1cW:wIH3lZZN2emWmIHHmeIVzKDNyIH3pcpMh[nliaX3teY5w[myxdITpcoc>	M{jh[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MkW4OVIyLz5{NkK1PFUzOTxxYU6=
BA/F3	M1HlNmZ2dmO2aX;uJIF{e2G7	M4nH[lMxOCCwTR?=	M1LxdVMhcHK\|	NVnCXnhEUW6qaXLpeIlwdiCxZjDKRWs{KCi3bnvuc5dvKG:{aXfpckkh\XiycnXzd4VlKGmwIH3veZNmKEKDL1[zJINmdGy\|IHHzd4V{e2WmIHHzJJJm\HWldHnvckBw\iCVVFHUOUBxcG:\|cHjvdplt[XSrb36gZZQhOzByIH7NJIFnfGW{IEOgbJJ{KGK7IHntcZVvd2Kub4T0bY5oKGGwYXz5d4l{	MnvKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ{NUi1NlEoRjJ4MkW4OVIyRC:jPh?=
OCL-AML5	M{nwVmZ2dmO2aX;uJIF{e2G7	NX\QZY9xOSC3TR?=	NWHZe4NiOyCqcoO=	MUPJcohq[mm2aX;uJI9nKEqDS{KgbY4hcHWvYX6gU2NNNUGPTEWgZ4VtdHNiYYPz[ZN{\WRiYYOgbY5pcWKrdHnvckBw\iCJTT3DV2YhcW6mdXPl[EBUXEGWNTDwbI9{eGixconsZZRqd25iYYSgNUB2VSCycnXpcoN2[mG2ZXSg[o9zKDNiaILzJIZwdGyxd3XkJIJ6KEePLVPTSkBqdmS3Y4Tpc44hdWWjc4Xy[YQh[W[2ZYKgN\|AhdWmwczDifUBqdW23bn;icI91fGmwZx?=	MoKxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ{NUi1NlEoRjJ4MkW4OVIyRC:jPh?=
BA/F3	M{K1bmFvfGmycn;sbYZmemG2aY\lJIF{e2G7		M4PKRVczKGi{cx?=	MYDBcpRqeHKxbHnm[ZJifGm4ZTDhZ5Rqfmm2eTDh[4FqdnO2IH3veZNmKEKDL1[zJINmdGy\|IHX4dJJme3OrbnegWGVNNUqDS{OgZYZ1\XJiN{KgbJJ{KGK7IHPlcIwhfGm2ZYKg[4xwKGG\|c3H5	M1LkVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MkW4OVIyLz5{NkK1PFUzOTxxYU6=
BA/F3	NWTzPIZETnWwY4Tpc44h[XO\|YYm=	M1S1dlEhfU1?	NUXk[FFoOyCqcoO=	MXzJcohq[mm2aX;uJI9nKEqDS{OgLJVvc26xd36gc5Jq\2mwKTDlfJBz\XO\|ZXSgbY4hdW:3c3WgRmEwTjNiY3XscJMh[XRiMTD1UUBxemWrbnP1ZoF1\WRiZn;yJFMhcHK\|IH\vcIxwf2WmIHL5JJB2dGymb4fuJJdqfGhic4Ty[ZB1[X[rZHnuJIJm[WS\|IHL5JIludXWwb3Lsc5R1cW6pIHHuZYx6e2m\|	MmPaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ{NUi1NlEoRjJ4MkW4OVIyRC:jPh?=
Huh7	NY[5O29GTnWwY4Tpc44h[XO\|YYm=	M{PSOVExKHWP	NXe2WYN1OzBibXnudy=>	NUXEcYpJUW6qaXLpeIlwdiCxZjDUfYszKGmwIHj1cYFvKEi3aEegZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJI9nKEmITnHsdIhiPS2rbnT1Z4VlKFOWQWSzJJBpd3OyaH;yfYxifGmxbjDheEAyOCC3TTDwdoUucW6ldXLheIVlKG[xcjCzNEBucW6\|IHLl[o9z\SCLRl7hcJBp[TVic4TpcZVt[XSrb36g[o9zKDNyIH3pcpMhdWmwczDifUBqdW23bn;icI91fGmwZx?=	MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjJ\|MUG1PUc,OjZ{M{GxOVk9N2F-
Huh7	NIfyZo1HfW6ldHnvckBie3OjeR?=	M3\QO\|ExKHWP	MoDuN\|AhdWmwcx?=	M1TYbmlvcGmkaYTpc44hd2ZiVInrNkBqdiCqdX3hckBJfWh5IHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDv[kBj[XOjbDDs[ZZmdCCVVFHUN{BxcG:\|cHjvdplt[XSrb36gZZQhOTBidV2gZYZ1\XJiM{CgcYlveyCkeTDpcY12dm:kbH;0eIlv\w>?	NGnHPHE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NkKzNVE2QSd-Mk[yN\|EyPTl:L3G+
Huh7	MV3GeY5kfGmxbjDhd5NigQ>?	MmrzNUB2VQ>?	M1\NRVMxKG2rboO=	M{f5UGlvcGmkaYTpc44hd2ZiVInrNkBqdiCqdX3hckBJfWh5IHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDv[kBKTk6jbIDoZVUucW6mdXPl[EBUXEGWMzDwbI9{eGixconsZZRqd25iYYSgNUB2VSCycnWtbY5kfWKjdHXkJIZweiB\|MDDtbY5{KGKnZn;y[UBKTk6jbIDoZVUhe3SrbYXsZZRqd25iZn;yJFMxKG2rboOgcYlveyCkeTDpcY12dm:kbH;0eIlv\w>?	M1fOT\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ4MkOxNVU6Lz5{NkKzNVE2QTxxYU6=

... 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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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.

Note：1.Please make sure the liquid is clear before adding the next solvent.
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The Serial Dilution Calculator Equation

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C1=C0/X	C1:	LOG(C1):
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Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2021-05-17)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
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
NCT04768504	Not yet recruiting	Drug: Tofacitinib 10 mg	Immune-Mediated Colitis	Khashayar Esfahani\|Sir Mortimer B. Davis - Jewish General Hospital	April 2021	Phase 2
NCT04624230	Recruiting	Drug: tofacitinib	Ulcerative Colitis	Pfizer	April 30 2021	Phase 3
NCT04424303	Recruiting	Drug: Tofacitinib	Ulcerative Colitis	Pfizer	December 7 2020	--
NCT04468425	Recruiting	Drug: Tofacitinib Citrate	Healthy Subjects	TWi Biotechnology Inc.	October 14 2020	Phase 1
NCT04576000	Recruiting	Drug: Tofacitinib	Ulcerative Colitis	Alimentiv Inc.	August 25 2020	--

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.

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)