R406

Name: R406
Brand: Selleck Chemicals
SKU: S2194
Rating: 5 (72 reviews)

For research use only.

Catalog No.S2194

72 publications

CAS No. 841290-81-1

R406 is a potent Syk inhibitor with IC50 of 41 nM in cell-free assays, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. R406 induces apoptosis. Phase 1.

Selleck's R406 has been cited by 72 publications

Cell, 2020, 182(3):685-712.e19

PubMed: 32645325 ( click the link to review the publication )

Cancer Cell, 2017, 31(4):549-562

PubMed: 28399410 ( click the link to review the publication )

Nat Med, 2016, 22(8):915-23

PubMed: 27428901 ( click the link to review the publication )

Sci Transl Med, 2021, 13(596)eabf8654

PubMed: 33979301 ( click the link to review the publication )

Cell Rep, 2021, 34(11):108870

PubMed: 33730585 ( click the link to review the publication )

Elife, 2021, 10e65962

PubMed: 33890572 ( click the link to review the publication )

Haematologica, 2021, 10.3324/haematol.2021.278743

PubMed: 34162179 ( click the link to review the publication )

Transl Res, 2021, 227:53-63

PubMed: 32687976 ( click the link to review the publication )

J Leukoc Biol, 2021, 10.1002/JLB.2A0520-334R

PubMed: 33884657 ( click the link to review the publication )

Am J Physiol Cell Physiol, 2021, 320(5):C902-C915

PubMed: 33689480 ( click the link to review the publication )

J Biol Chem, 2021, S0021-9258(21)00238-6

PubMed: 33639170 ( click the link to review the publication )

Cell Death Dis, 2020, 11(11):956

PubMed: 33159047 ( click the link to review the publication )

Front Immunol, 2020, 11:610523

PubMed: 33552071 ( click the link to review the publication )

Aging (Albany NY), 2020, 7;12(9):8221-8240

PubMed: 32379705 ( click the link to review the publication )

Biomolecules, 2020, 10(9)E1283

PubMed: 32899943 ( click the link to review the publication )

Int J Mol Sci, 2020, 21(19)E7009

PubMed: 32977621 ( click the link to review the publication )

[email protected], 2020, 51

PubMed: N/A ( click the link to review the publication )

[email protected], 2020, None

PubMed: None ( click the link to review the publication )

Nat Cell Biol, 2019, 21(2):203-213

PubMed: 30664786 ( click the link to review the publication )

mBio, 2019, 10(3)e00574-19

PubMed: 31064828 ( click the link to review the publication )

PLoS Pathog, 2019, 15(8):e1007923

PubMed: 31449558 ( click the link to review the publication )

Cell Death Dis, 2019, 10(8):555

PubMed: 31324751 ( click the link to review the publication )

Front Immunol, 2019, 10:921

PubMed: 31139177 ( click the link to review the publication )

J Immunol, 2019, 203(12):3225-3236

PubMed: 31704879 ( click the link to review the publication )
Molecules, 2019, 24(20)E3640

PubMed: 31600968 ( click the link to review the publication )

PLoS One, 2019, 14(1):e0210879

PubMed: 30668583 ( click the link to review the publication )

Mucosal Immunol, 2019, 12(2):425-433

PubMed: 30664707 ( click the link to review the publication )

J Control Release, 2018, 288:227-238

PubMed: 30219279 ( click the link to review the publication )

J Bone Miner Res, 2018, 33(1):167-181

PubMed: 28914985 ( click the link to review the publication )

Front Immunol, 2018, 9:37

PubMed: 29410669 ( click the link to review the publication )

J Mol Cell Cardiol, 2018, 115:82-93

PubMed: 29274344 ( click the link to review the publication )

Cell Microbiol, 2018, 20(2)

PubMed: 29125705 ( click the link to review the publication )

Chem Res Toxicol, 2018, 31(2):127-136

PubMed: 29156121 ( click the link to review the publication )

Leukemia, 2017, 31(8):1686-1694

PubMed: 27890932 ( click the link to review the publication )

Cancer Res, 2017, 77(8):1818-1830

PubMed: 28130226 ( click the link to review the publication )

EMBO Rep, 2017, 18(9):1604-1617

PubMed: 28705801 ( click the link to review the publication )

Mol Cancer Ther, 2017, 16(11):2586-2597

PubMed: 28835384 ( click the link to review the publication )

J Immunol, 2017, 198(8):3181-3194

PubMed: 28264968 ( click the link to review the publication )

PLoS Comput Biol, 2017, 13(3):e1005432

PubMed: 28306714 ( click the link to review the publication )

Oncotarget, 2017, 8(7):10931-10944

PubMed: 28077790 ( click the link to review the publication )

Clin Immunol, 2017, 175:69-74

PubMed: 27919819 ( click the link to review the publication )

Blood, 2017, 129(6):759-770

PubMed: 28011673 ( click the link to review the publication )

Blood, 2016, 127(25):3192-201

PubMed: 27095788 ( click the link to review the publication )

Leukemia, 2016, 30(5):1116-25

PubMed: 26867669 ( click the link to review the publication )

Cancer Res, 2016, 76(23):6937-6949

PubMed: 27758892 ( click the link to review the publication )

Cell Death Differ, 2016, 23(4):628-39

PubMed: 26450454 ( click the link to review the publication )

J Invest Dermatol, 2016, 136(1):192-201

PubMed: 26763439 ( click the link to review the publication )

PLoS Pathog, 2016, 12(3):e1005487

PubMed: 26943817 ( click the link to review the publication )
PLoS Genet, 2016, 12(9):e1006279

PubMed: 27588951 ( click the link to review the publication )

PLoS One, 2016, 11(10):e0164895

PubMed: 27768734 ( click the link to review the publication )

J Allergy Clin Immunol, 2016, 138(3):839-851

PubMed: 27056269 ( click the link to review the publication )

Nat Cell Biol, 2015, 17(1):57-67

PubMed: 25487280 ( click the link to review the publication )

Blood, 2015, 126(16):1911-20

PubMed: 26272216 ( click the link to review the publication )

Leukemia, 2015, 29(6):1350-9

PubMed: 25482129 ( click the link to review the publication )

Mol Syst Biol, 2015, 11(1):789

PubMed: 25699542 ( click the link to review the publication )

J Leukoc Biol, 2015, 10.1189/jlb.3HI0814-371RR

PubMed: 25605870 ( click the link to review the publication )

Sci Rep, 2015, 5:16995

PubMed: 26592927 ( click the link to review the publication )

J Biomol Screen, 2015, 10.1177/1087057115585724

PubMed: 25948491 ( click the link to review the publication )

Immunity, 2014, 40(3):389-99

PubMed: 24631154 ( click the link to review the publication )

Blood, 2014, 124(4):590-7

PubMed: 24948657 ( click the link to review the publication )

J Clin Invest, 2014, 124(11):5074-84

PubMed: 25329694 ( click the link to review the publication )

Nat Commun, 2014, 5:5444

PubMed: 25392121 ( click the link to review the publication )

J Bone Miner Res, 2014, 29(12):2618-35

PubMed: 24916406 ( click the link to review the publication )

Eur J Med Chem, 2014, 86C:664-675

PubMed: 25222877 ( click the link to review the publication )

Eur J Immunol, 2014, 44(12):3729-40

PubMed: 25251945 ( click the link to review the publication )

Exp Cell Res, 2014, 322(1):99-107

PubMed: 24406398 ( click the link to review the publication )

PLoS One, 2014, 9(5):e96703

PubMed: 24846290 ( click the link to review the publication )

Exp Dermatol, 2014, 23(12):884-9

PubMed: 25267545 ( click the link to review the publication )

Blood, 2013, 122(4):580-9

PubMed: 23699602 ( click the link to review the publication )

Clin Cancer Res, 2013, 19(3):586-97

PubMed: 23231952 ( click the link to review the publication )

Br J Haematol, 2013, 163(5):590-602

PubMed: 24117128 ( click the link to review the publication )

UVIC, 2013, Meritxell Aguiló García

PubMed: ( click the link to review the publication )

Purity & Quality Control

Choose Selective Syk Inhibitors

Biological Activity

Description

R406 is a potent Syk inhibitor with IC50 of 41 nM in cell-free assays, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. R406 induces apoptosis. Phase 1.

Features

Lead drug candidate for rheumatoid arthritis.

Targets

Flt3 ^[1] (Cell-free assay)	Syk ^[1] (Cell-free assay)
	41 nM

In vitro

R406 is a potent inhibitor of immunoglobulin E (IgE)- and IgG-mediated activation of Fc receptor signaling. R406 inhibits the anti-IgE-induced production and release of LTC4 and cytokines and chemokines, including TNFα, IL-8, and GM-CSF. R406 inhibits phosphorylation of Syk substrate linker for activation of T cells in mast cells and B-cell linker protein/SLP65 in B cells. R406 binds to the ATP binding pocket of Syk and inhibits its kinase activity as an ATP-competitive inhibitor with K_i of 30 nM. R406 blocks Syk-dependent FcR-mediated activation of monocytes/macrophages and neutrophils and Bcr-mediated activation of B lymphocytes. ^[1] R406 significantly induces chronic lymphocytic leukemia (CLL) cell apoptosis in nurselike cells cocultures and blocks CCL3 and CCL4 secretion by CLL cells in response to B-cell antigen receptor (Bcr) triggering. ^[2] R406 is a potent inhibitor of platelet signaling and functions initiated by FcγRIIA cross-linking by specific antibodies or by sera from HIT patients. ^[3]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID
AMO-1	NYDkdVZ6TnWwY4Tpc44hSXO\|YYm=	MofrNUDPxE1?	MYmzxsBp		M{nsS5Jm\HWlZYOgcYloemG2aX;uxsA>	NX;tZ21MRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[yOVE4PjFpPkK2NlUyPzZzPD;hQi=>
U266	MnPwSpVv[3Srb36gRZN{[Xl?	NEe4SXMyKM7:TR?=	MXOzxsBp		MlH3doVlfWOnczDtbYdz[XSrb39CpC=>	MlTxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjZ{NUG3OlEoRjJ4MkWxO\|YyRC:jPh?=
Jeko-1	M2TUZWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		NUfrNIp[PDhiaB?=		MU\JR\|UxRTVwME[4NlYh\|ryP	MlvjQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6M{W3OVUoRjJ3OEO1O\|U2RC:jPh?=
Mino	MYnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?		MkTLOFghcA>?		MV3JR\|UxRTVwN{C4OVQh\|ryP	NFXkZYw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOVc2PSd-MkW4N\|U4PTV:L3G+
Jeko-1	NWj2fVVHSXCxcITvd4l{KEG\|c3H5	NHTSNGk2yqEQvF2=	NH62WFgzPCCq		M3[4eYlv\HWlZYOgNlUvOcLiwsJCpFMvOsLiJTDhdI9xfG:\|aYO=	NH7Udlc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUizOVc2PSd-MkW4N\|U4PTV:L3G+
primary MCL	Mm\4RZBweHSxc3nzJGF{e2G7	NE[2[\|czKML3TR?=	MXKyOEBp		MVvpcoNz\WG\|ZYOgd4lodmmoaXPhcpRtgSCjcH;weI9{cXQEoB?=	M2TZ[\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3M{i4N\|c{Lz5{NUO4PFM4OzxxYU6=
PBMCs	MX;D[YxtKF[rYXLpcIl1gSCDc4PhfS=>	MUSwMVUxKM7:TR?=	NHriZ2wzPCCq	M32ydmROW09?	NWLNTFFVcW6qaXLpeJMh[2WubDD2bYFjcWyrdImg[I9{\SCmZYDlcoRmdnSueR?=	M1\UPFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MUK3PFYzLz5{NUGyO\|g3OjxxYU6=
PBMCs	NELmUIRHfW6ldHnvckBCe3OjeR?=	Mm\TOUDPxE1?	NH;wO4EyKGh?	M2LtUGROW09?	NWHobZJn\GWlcnXhd4V{KHSqZTDj[YxtKG2rZ4LheIlwdg>?	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTF{N{i2Nkc,OjVzMke4OlI9N2F-
CFSE-CD4+ T	MlfiS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl?	NED2b\|kxNjB4MkWtNUDPxE1?	MWi0JIQ>		M4SxeYJtd2OtczDwdo9tcW[ncnH0bY9vKG:oIFfWTGQu\GW{aY\l[EBETDRtwrDUJINmdGy\|IHHu[EBETDFzYjxCpINmdGy\|	MnH6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4N{m5PFIoRjJ2Nke5PVgzRC:jPh?=
CFSE-CD11b+	M4m3OWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MX6wMlA3OjVvMTFOwG0>	MmjzPEBl		NFXUe\|ZjdG:la4OgdJJwdGmoZYLheIlwdiCxZjDHWmhFNWSncnn2[YQhS0R2K9MgWEBk\WyuczDhcoQhS0RzMXKrxsBk\Wyucx?=	MnPYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR4N{m5PFIoRjJ2Nke5PVgzRC:jPh?=
HMECs	MYPGeY5kfGmxbjDBd5NigQ>?	MYqwMVExKM7:TR?=	NFjDUHgzOCCvaX6=		NF3zTphqdmirYnn0d{BXTUeILYP0bY12dGG2ZXSgdoVt\WG\|ZTDv[kBPVw>?	M3zQ[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{K5OVQ1Lz5{NEOyPVU1PDxxYU6=
AB5	MU\BdI9xfG:\|aYOgRZN{[Xl?	MluxNE0zNjVizszN	NFzOdmE1QCCq	MXzEUXNQ	NYPwbGpCcW6mdXPld{BieG:ydH;zbZM>	MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzN7OEmxNUc,OjN\|OUi5NVE9N2F-
JB7	MonQRZBweHSxc3nzJGF{e2G7	M4Tae\|AuOi53IN88US=>	MV[0PEBp	M2rKdGROW09?	M4f1Xolv\HWlZYOgZZBweHSxc3nz	MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzN7OEmxNUc,OjN\|OUi5NVE9N2F-
AB5	M4LJb2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M1H6UFAuOi53IN88US=>	MlPGOFghcA>?	NVXhVlA{TE2VTx?=	MlHBbY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dB?=	Mmi4QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN\|OUi5NVEoRjJ\|M{m4PVEyRC:jPh?=
JB7	NGCxc\|ZIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	M{L6NlAuOi53IN88US=>	M{nhVFQ5KGh?	NXiyfYZmTE2VTx?=	MkHmbY5lfWOnczDj[YxtKGO7Y3zlJIFzemW\|dB?=	NGS0XXk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{O5PFkyOSd-MkOzPVg6OTF:L3G+
RL	NIrFVYpHfW6ldHnvckBCe3OjeR?=	NYryPFY2Oi53L{Wg{txO	NU\VOm1mOjRxNEigbC=>	NWrGbIVwTE2VTx?=	MkXvbY5lfWOnczDhJJBwfGWwdDDk[YNz\WG\|ZTDpckBOVVBvOTDtVm5CKGW6cILld5Nqd25?	NVrsXopHRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5NlY6PjVpPkKxPVI3QTZ3PD;hQi=>
RL	M4rNTmZ2dmO2aX;uJGF{e2G7	NV7Ke2tPOS9{LkWg{txO	MVSyOEBp	Mo\TSG1UVw>?	M2Lhb5Jm\HWlZYOgeIhmKGGldHn2ZZRqd25ib3[gRYt1KGGwZDDwO\|BUPkt?	M{LrTVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOUK2PVY2Lz5{MUmyOlk3PTxxYU6=
platelet	MmnSSpVv[3Srb36gRZN{[Xl?	M{j2UFHDqM7:bR?=	M{jPS\|UhdWmw		NYjqOGN[cW6qaXLpeJMhTmQQs2LJTWEudWWmaXH0[YQheGyjdHXs[ZQh[WepcnXnZZRqd25?	NFS1NIE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUi0PFY6PCd-MkG4OFg3QTR:L3G+
platelet	MoC3SpVv[3Srb36gRZN{[Xl?	NEjSSFkxNjB3L{GvNk42KM7:TR?=	MonXOUBucW5?		MWnpcohq[mm2czD0bIUhe2mpbnHsbY5oKG2nY3jhcol{dXNiZH;3cpN1emWjbTDv[kBH[87\|UlnJRS=>	MkjTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF6NEi2PVQoRjJzOES4Olk1RC:jPh?=
DoHH2	NFi4d5BCeG:ydH;zbZMhSXO\|YYm=	M4rOdVAwOy9zMDFOwG0>	M17EVFQ5KGh?		MUfpcoR2[2W\|IHPlcIwh\GWjdHigd4lodmmoaXPhcpRtgQ>?	MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zODh5NUSwPEc,OjB6N{W0NFg9N2F-
Jeko-1	MoTWRZBweHSxc3nzJGF{e2G7	NGHu[XExNzNxMUCg{txO	MXy0PEBp		MWHpcoR2[2W\|IHPlcIwh\GWjdHigd4lodmmoaXPhcpRtgQ>?	NU\rfWVURGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkC4O\|U1ODhpPkKwPFc2PDB6PD;hQi=>
Raji	NH7uTZVCeG:ydH;zbZMhSXO\|YYm=	MX6wM\|MwOTBizszN	NFzmXpc1QCCq		MYjpcoR2[2W\|IHPlcIwh\GWjdHigd4lodmmoaXPhcpRtgQ>?	MonxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB6N{W0NFgoRjJyOEe1OFA5RC:jPh?=
DHL4	NIfkZo1CeG:ydH;zbZMhSXO\|YYm=	M2LX[VAwOS92IN88US=>	NXy4dJlLQTZiaB?=		NFG2bItqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5	MmrYQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyME[2PVYoRjF6MEC2Olk3RC:jPh?=
LY7	NGfWRlFCeG:ydH;zbZMhSXO\|YYm=	M3\YbVAwOS92IN88US=>	NVnlOHZsQTZiaB?=		M4TKRYlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm=	MYq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDByNk[5Okc,OThyME[2PVY9N2F-
LY3	Mmr0RZBweHSxc3nzJGF{e2G7	NX\nW5lFOC9zL{Sg{txO	M3PrWlk3KGh?		MljQbY5lfWOnczDhdI9xfG:\|aYOg[I9{\SCmZYDlcoRmdnSueR?=	NX3ISW9tRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUiwNFY3QTZpPkG4NFA3Pjl4PD;hQi=>
DHL6	NEXuXYlCeG:ydH;zbZMhSXO\|YYm=	M{jmXlAwOS92IN88US=>	NEHtWG06PiCq		NUT3WIpGcW6mdXPld{BieG:ydH;zbZMh\G:\|ZTDk[ZBmdmSnboTsfS=>	Mon5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyME[2PVYoRjF6MEC2Olk3RC:jPh?=
LY10	NVe0WnhWSXCxcITvd4l{KEG\|c3H5	MoW3NE8yNzRizszN	NVG1doVwQTZiaB?=		MYTpcoR2[2W\|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7	MmjaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyME[2PVYoRjF6MEC2Olk3RC:jPh?=
DHL10	NHPpV5pCeG:ydH;zbZMhSXO\|YYm=	NFTE[G4xNzFxNDFOwG0>	M3fSVVk3KGh?		NHzQSXdqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5	MorFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyME[2PVYoRjF6MEC2Olk3RC:jPh?=
Wsu-NHL	NGnmfI9CeG:ydH;zbZMhSXO\|YYm=	M2LYS\|AwOS92IN88US=>	MWG5OkBp		NUjrcJo2cW6mdXPld{BieG:ydH;zbZMh\G:\|ZTDk[ZBmdmSnboTsfS=>	NVruWZZwRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUiwNFY3QTZpPkG4NFA3Pjl4PD;hQi=>
LY18	NYn4[3dQSXCxcITvd4l{KEG\|c3H5	NYDE[2x4OC9zL{Sg{txO	NFLJTlc6PiCq		M3H5O4lv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm=	M3LLcFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6MEC2Olk3Lz5zOECwOlY6PjxxYU6=
LY1	M4DaOmFxd3C2b4Ppd{BCe3OjeR?=	M3q2NlAwOS92IN88US=>	NEXkfYU6PiCq		M4XUfYlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm=	MmHsQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyME[2PVYoRjF6MEC2Olk3RC:jPh?=
DHL8	NG\yRoNCeG:ydH;zbZMhSXO\|YYm=	MoDPNE8yNzRizszN	NGLweHc6PiCq		M1vYcIlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm=	NY[0XllGRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUiwNFY3QTZpPkG4NFA3Pjl4PD;hQi=>
DHL4	MULBdI9xfG:\|aYOgRZN{[Xl?	NUX2O\|k4PCEQvF2=	NF\J[VQ6PiCq		M4i1VIlv\HWlZYOgZ4xm[X[jZ3Wgc4Yh[2G\|cHHz[ZMhQSCjbnSgN{wh[nW2IH7veEBk[XOyYYPlJFg>	NULXOm9rRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUiwNFY3QTZpPkG4NFA3Pjl4PD;hQi=>
DHL6	MXjBdI9xfG:\|aYOgRZN{[Xl?	MoTaOEDPxE1?	MXW5OkBp		NIi4dYZqdmS3Y3XzJINt\WG4YXflJI9nKGOjc4Dhd4V{KDliYX7kJFMtKGK3dDDuc5Qh[2G\|cHHz[UA5	MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDByNk[5Okc,OThyME[2PVY9N2F-
LY3	M{nqR2Fxd3C2b4Ppd{BCe3OjeR?=	MkWyOEDPxE1?	NGTMXY06PiCq		NWLlcnBYcW6mdXPld{BkdGWjdnHn[UBw\iClYYPwZZNmeyB7IHHu[EA{NCCkdYSgco91KGOjc4Dhd4UhQA>?	MUm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDByNk[5Okc,OThyME[2PVY9N2F-
LY7	NUTCdnduSXCxcITvd4l{KEG\|c3H5	NU\4UVRjPCEQvF2=	NV;rR3BYQTZiaB?=		MluzbY5lfWOnczDjcIVifmGpZTDv[kBk[XOyYYPld{A6KGGwZDCzMEBjfXRibn;0JINie3Cjc3WgPC=>	MV28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDByNk[5Okc,OThyME[2PVY9N2F-
DHL4	MWXGeY5kfGmxbjDBd5NigQ>?	MXu0JO69VQ>?	NXO2THZFOTZiaB?=		M3\vdolvcGmkaYTzJJRwdmmlIFLMUmshfHm{b4PpcoUheGixc4Doc5J6dGG2aX;u	M1zFRlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6MEC2Olk3Lz5zOECwOlY6PjxxYU6=
LY7	Mmi5SpVv[3Srb36gRZN{[Xl?	M2jIb\|Qh\|ryP	M3PiPVE3KGh?		Ml;ubY5pcWKrdIOgeI9vcWNiQlzOT{B1gXKxc3nu[UBxcG:\|cHjvdplt[XSrb36=	MnnpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyME[2PVYoRjF6MEC2Olk3RC:jPh?=
LY3	MoHISpVv[3Srb36gRZN{[Xl?	Ml;MOEDPxE1?	NE[4[moyPiCq		NFzaXXlqdmirYnn0d{B1d26rYzDCUG5MKHS7cn;zbY5mKHCqb4PwbI9zgWyjdHnvci=>	MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDByNk[5Okc,OThyME[2PVY9N2F-
DHL6	Mn7ZSpVv[3Srb36gRZN{[Xl?	NGXEPI01KM7:TR?=	MofPNVYhcA>?		NELxXIlqdmirYnn0d{B1d26rYzDCUG5MKHS7cn;zbY5mKHCqb4PwbI9zgWyjdHnvci=>	NVfFfXljRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUiwNFY3QTZpPkG4NFA3Pjl4PD;hQi=>
LY10	NGHvOnRHfW6ldHnvckBCe3OjeR?=	NIflWIo1KM7:TR?=	NHTGWGIyPiCq		M3PhOolvcGmkaYTzJJRwdmmlIFLMUmshfHm{b4PpcoUheGixc4Doc5J6dGG2aX;u	MoHtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyME[2PVYoRjF6MEC2Olk3RC:jPh?=
Wsu-NHL	NVjqN3B1TnWwY4Tpc44hSXO\|YYm=	NF:yOWo1KM7:TR?=	M2HUR\|E3KGh?		MkK1bY5pcWKrdIOgeI9vcWNiQlzOT{B1gXKxc3nu[UBxcG:\|cHjvdplt[XSrb36=	MkTtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyME[2PVYoRjF6MEC2Olk3RC:jPh?=
LY18	NUfHZnN1TnWwY4Tpc44hSXO\|YYm=	MV20JO69VQ>?	NEL3NZoyPiCq		M1zab4lvcGmkaYTzJJRwdmmlIFLMUmshfHm{b4PpcoUheGixc4Doc5J6dGG2aX;u	NF[0T2E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOECwOlY6Pid-MUiwNFY3QTZ:L3G+
MV411	MojMSpVv[3Srb36gZZN{[Xl?		MVm3NkBpenN?		NFfDb5hKdmirYnn0bY9vKG:oIF\seFMhcW5iaIXtZY4hVVZ2MUGgZ4VtdHNiYYPz[ZN{\WRiYYOgZZN{\XO\|ZXSgZZMheHKxbHnm[ZJifGmxbjDh[pRmeiB5MjDodpMhcW6ldXLheIlwdiCkeTDzdIVkfHKxcHjveI9u\XS{eTygSWM2OD1yLkCx{txONg>?	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDd5OUWxOEc,OjR5N{m1NVQ9N2F-
TF1	MUDGeY5kfGmxbjDhd5NigQ>?		NEHyT5kyKGi{		MUXJcohq[mm2aX;uJI9nKEqja{KgbY4h\XK7dHjyc5BwcWW2aX6td5RqdXWuYYTl[EBpfW2jbjDUSlEh[2WubIOgZZN{\XO\|ZXSgZZMh[XO\|ZYPz[YQh[XNicHjvd5Bpdy2VdHH0OUBi\nSncjCxJIhzKGmwY4XiZZRqd25uIFXDOVA:OC5yMUROwG0v	MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDd5OUWxOEc,OjR5N{m1NVQ9N2F-
neutrophils	NIjubGZHfW6ldHnvckBie3OjeR?=				NXHPe4hMUW6qaXLpeIlwdiCxZjDTXWshcW5iaIXtZY4hdmW3dILvdIhqdHNiY3XscJMh[XO\|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJGZk\XC\|aXzvcnIyN0[lZ3HtcYFTNW2nZHnheIVlKHOrZ37hcIlv\yC{ZYPwc45{\XNuIFXDOVA:OC5yM{ROwG0v	MoGzQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ{NUeyNVMoRjJ{MkW3NlE{RC:jPh?=
SK-M-MC	NYTjNIZYTnWwY4Tpc44h[XO\|YYm=		Mn71NUBpeg>?		NF7CT5dKdmirYnn0bY9vKG:oIGLleEBqdiCqdX3hckBUUy2PLV3DJINmdGy\|IHHzd4V{e2WmIHHzJIF{e2W\|c3XkJIF{KHCqb4PwbI9zgWyjdHnvckBi\nSncjCxJIhzKGmwY4XiZZRqd25uIFXDOVA:OC5yM{dOwG0v	NYPSXWJ2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS3O\|k2OTRpPkK0O\|c6PTF2PD;hQi=>
mast cells	MojVSpVv[3Srb36gZZN{[Xl?		M{SyRVEhcHJ?		MkPSTY5pcWKrdHnvckBw\iClS3n0JIlvKHO2ZX2gZ4VtdCCoYXP0c5Iue3SrbYXsZZRm\CCkb37lJI1ienKxdzDk[ZJqfmWmIH3veZNmKG2jc4SgZ4VtdHNiYYPz[ZN{\WRiYYOgdIhwe3Cqb4L5cIF1cW:wIHHmeIVzKDFiaIKgbY5kfWKjdHnvckwhTUN3ME2wMlA1Ps7:TT6=	NEf3U5Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe3PVUyPCd-MkS3O\|k2OTR:L3G+
B-cells	NITaNoxHfW6ldHnvckBie3OjeR?=				M3:2XmlvcGmkaYTpc44hd2ZiU2nLJIlvKGi3bXHuJGIu[2WubIOgZ4VtdHNiYYPz[ZN{\WRiYYOgdoVlfWO2aX;uJIlvKE[lZYDzbYxwdlJzL1\j[4FudWGULX3l[IlifGWmIIPp[45idGmwZzDy[ZNxd26\|ZYOsJGVEPTB;MD6wOFjPxE1w	NIT0elc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkK1O\|IyOyd-MkKyOVczOTN:L3G+
Ramos	M4L4SmZ2dmO2aX;uJIF{e2G7				M3T3R2lvcGmkaYTpc44hd2ZiU4nrJIlvKGGwdHnoeY1idiCLZ12td5RqdXWuYYTl[EBpfW2jbjDSZY1weyClZXzsd{Bie3Onc4Pl[EBieyCmZXPy[YF{\SCrbjDCR3IudWWmaXH0[YQhSkyQSzDwbI9{eGixconsZZRqd25iYomgZ4VtdHWuYYKgZZN{[XluIFXDOVA:OC5yNUROwG0v	NI\Ddnk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe3PVUyPCd-MkS3O\|k2OTR:L3G+
mesangial cells	NVO0bllvTnWwY4Tpc44h[XO\|YYm=				NXjVcGdTUW6qaXLpeIlwdiCxZjDTXWshcW5iY4XseJVz\WRiaIXtZY4hdWW\|YX7nbYFtKGOnbHzzJIF{e2W\|c3XkJIF{KHKnZIXjeIlwdiCrbjDGZ4Vxe2mub37SNU9H[2ejbX3hVk1u\WSrYYTl[EB{cWewYXzpcochemW\|cH;ud4V{NCCHQ{WwQVAvODV4zszNMi=>	NX7mdWdNRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKyOVczOTNpPkKyNlU4OjF\|PD;hQi=>
SK-N-SH	NEWwS2dHfW6ldHnvckBie3OjeR?=				MXrJcohq[mm2aX;uJI9nKFKndDDpckBpfW2jbjDTT{1PNVOKIHPlcIx{NCCHQ{WwQVAvODkQvF2u	MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjJ3N{KxN{c,OjJ{NUeyNVM9N2F-
mouse bone marrow cells	NIjvcIpHfW6ldHnvckBie3OjeR?=				NUHUfY8{UW6qaXLpeIlwdiCxZjDJUFMh\GWyZX7k[Y51KHC{b3zp[oVz[XSrb36gbY4hSzV5L1KxOkBud3W\|ZTDic45mKG2jcoLve{Bk\WyuczD1d4lv\yCdM1jdeIh6dWmmaX7lJIJ6KGyrcYXp[EB{[2mwdHnscIF1cW:wIHPveY51cW6pLDDJR\|UxRTBwMUS3{txONg>?	MVy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDd{NkiwOkc,OjR5Mk[4NFY9N2F-
B-cells	NH7PXHNHfW6ldHnvckBie3OjeR?=		NYfHZnJQOSCqch?=		Mo\STY5pcWKrdHnvckBw\iCVeXugbY4h[WyyaHHJ[20ue3SrbYXsZZRm\CCqdX3hckBDKGOnbHzzJIF{e2W\|c3XkJIF{KGOnbHygdJJwdGmoZYLheIlwdiCjZoTldkAyKGi{IHnuZ5Vj[XSrb36gZpkh\myxdzDjfZRwdWW2comsJGVEPTB;MD6xOVHPxE1w	MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDd5OUWxOEc,OjR5N{m1NVQ9N2F-
THP1	Mn;ySpVv[3Srb36gZZN{[Xl?				NGPZdnBKdmirYnn0bY9vKG:oIGPZT{BqdiCqdX3hckBVUFBzIHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDpckBH[2Wyc3nsc45TOS:IY3fhcY1iWi2vZXTpZZRm\CC\|aXfuZYxqdmdicnXzdI9ve2W\|LDDFR\|UxRTBwMUex{txONg>?	M{T5WFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MkW3NlE{Lz5{MkK1O\|IyOzxxYU6=
B-cells	MX\GeY5kfGmxbjDhd5NigQ>?		M2DyS\|EhcHJ?		NFXSZoFKdmirYnn0bY9vKG:oIGP5b{BqdiCjbIDoZWloVS2\|dHnteYxifGWmIHj1cYFvKEJiY3XscJMh[XO\|ZYPz[YQh[XNiQ1S4OkBmgHC{ZYPzbY9vKGGodHXyJFEhcHJiaX7jeYJifGmxbjDifUBndG:5IHP5eI9u\XS{eTygSWM2OD1yLkOzOe69VS5?	NFrOdpo9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe3PVUyPCd-MkS3O\|k2OTR:L3G+
Ramos	NYLmTG01TnWwY4Tpc44h[XO\|YYm=				NILwOVRKdmirYnn0bY9vKG:oIGP5b{BqdiCjboTpJGloVS2\|dHnteYxifGWmIHj1cYFvKFKjbX;zJINmdGy\|IHHzd4V{e2WmIHHzJGJNVkticHjvd5Bpd3K7bHH0bY9vKGK7IHPlcIx2dGG{IHHzd4F6NCCLQ{WwQVAvPDV5zszNMi=>	NFfkblg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEeyOlgxPid-MkS3NlY5ODZ:L3G+
Rec1	MXzGeY5kfGmxbjDhd5NigQ>?	MXWyMlUhfU1?	MoHHOkBpenN?		M2DKVGlvcGmkaYTpc44hd2ZiQmTLJJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDS[YMyKGOnbHzzJIF1KDJwNTD1UUBqdmO3YnH0[YQh\m:{IE[gbJJ{KGK7IGfld5Rmem5iYnzveJRqdmdibXX0bI9l	MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTJ{Mki3O{c,OjV{MkK4O\|c9N2F-
Rec1	MUfGeY5kfGmxbjDhd5NigQ>?	M1L6WVIvPSC3TR?=	NYLFclJLPiCqcoO=		MkLkTY5pcWKrdHnvckBw\iCVeXugdIhwe3Cqb4L5cIF1cW:wIHnuJIh2dWGwIGLlZ\|Eh[2WubIOgZZQhOi53IIXNJIlv[3WkYYTl[EBnd3JiNjDodpMh[nliV3XzeIVzdiCkbH;0eIlv\yCvZYToc4Q>	NEn1XlM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUKyNlg4Pyd-MkWyNlI5Pzd:L3G+
Rec1	NYOwfZc2TnWwY4Tpc44h[XO\|YYm=	Mni4Nk42KHWP	MnnYOkBpenN?		NXrNNpY3UW6qaXLpeIlwdiCxZjDMfY4heGixc4Doc5J6dGG2aX;uJIlvKGi3bXHuJHJm[zFiY3XscJMh[XRiMj61JJVOKGmwY4XiZZRm\CCob4KgOkBpenNiYomgW4V{fGW{bjDicI91fGmwZzDt[ZRpd2R?	NELyenU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUKyNlg4Pyd-MkWyNlI5Pzd:L3G+
SJ-GBM2	M{K5R5FJXFNiYYPzZZk>				NF3USo9yUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiU1qtS2JOOiClZXzsdy=>	NXnhVohnRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
A673	NVLYTYN5eUiWUzDhd5NigQ>?				NHvmXmlyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiQU[3N{Bk\Wyucx?=	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
SK-N-MC	M4PZOJFJXFNiYYPzZZk>				NWG2[pc{eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPLMW4uVUNiY3XscJM>	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
NB-EBc1	NHX0UZpyUFSVIHHzd4F6				NELk[opyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiTlKtSWJkOSClZXzsdy=>	NYXTdWs{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Saos-2	M4jpb5FJXFNiYYPzZZk>				NY\vS4QyeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPhc5MuOiClZXzsdy=>	MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
OHS-50	NY\nc411eUiWUzDhd5NigQ>?				MYrxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhV0iVLUWwJINmdGy\|	NIr1WWw9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
Rh41	NYLEcldpeUiWUzDhd5NigQ>?				MWnxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhWmh2MTDj[Yxtew>?	M{PFblxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=

... Click to View More Cell Line Experimental Data

Assay

Methods	Test Index	PMID
Western blot	p-RPS6 / T-RPS6 / p-4E-BP1 / T-4E-BP1; PubMed: 23535559 Leukemia Four AML cell lines (a and b) were treated for 24 hours with vehicle versus R406. Western blots of (a) p-RPS6 (Ser240/244) and (b) p-4E-BP1 (Thr37/46). p-MEK / T-MEK / p-ERK / T-ERK; PubMed: 23535559 Leukemia AML cell lines were treated with vehicle versus R406. Western blots of p-MEK1/2 (Ser217/221) and p-ERK1/2 (Thr202/Tyr204) are depicted. p-c-RAF / T-c-RAF; PubMed: 23535559 Leukemia Effect of SYK inhibition on c-RAF in AML cells. AML cells were grown in the presence of 4 μM R406 for the indicated times and assessed for activation of c-RAF and ERK1/2. p-AKT / T-AKT / p-mTOR / T-mTOR; PubMed: 23535559 Leukemia Western blot of (a) p-AKT (Ser473) or (b) p-mTOR (Ser2448) in AML cell lines treated with R406 for 24 hours.	23535559
Growth inhibition assay	Cell viability (U87, U251 cells); PubMed: 31043589 Cell Death Dis U87 and U251 were insensitive to R406, with a calculated IC50 of more than 1 mM for both cell lines. Cell viability (GSC lines); PubMed: 31043589 Cell Death Dis Incubation with R406 significantly reduced the cell viability of both GSC lines, with an IC50 of 0.75 μM for GSC-1 and 0.89 μM for GSC-2 respectively.	31043589

In vivo

R406 reduces cutaneous reverse passive Arthus reaction by approximately 86% at 5 mg/kg in prophylactic treated mice. R406 also shows efficacy in inhibiting paw inflammation in antibody-induced arthritis mouse models. ^[1] R406 does not adversely affect macrophage or neutrophil function in innate immune responses and has minimal functional immunotoxicity notwithstanding its lymphocytopenic effect. ^[4]

Protocol

Animal Research:^[1]	- Collapse Animal Models: Arthritis is induced in C57BL/6 mice by intraperitoneal injection of 150 μL of pooled sera from adult K/BxN mice. Dosages: 1 or 5 mg/kg Administration: Administered orally (Only for Reference)

References

[4] Zhu Y, et al. Toxicol Appl Pharmacol, 2007, 221(3), 268-277.

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Solubility (25°C)

In vitro	DMSO	100 mg/mL (159.07 mM)
	Water	Insoluble
	Ethanol	0 mg/mL (0.0 mM)
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 5%dmso+95%cornoil For best results, use promptly after mixing.	6mg/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 R406 SDF

Molecular Weight	628.63
Formula	C₂₂H₂₃FN₆O₅.C₆H₆O₃S
CAS No.	841290-81-1
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CC1(C(=O)NC2=C(O1)C=CC(=N2)NC3=NC(=NC=C3F)NC4=CC(=C(C(=C4)OC)OC)OC)C.C1=CC=C(C=C1)S(=O)(=O)O

In vivo Formulation Calculator (Clear solution)

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

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mg/kg

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

% DMSO+ % + % Tween 80+ % ddH₂O

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Calculation results:

Working concentration： mg/ml；

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

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

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

Bio Calculators

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration _(start) x Volume _(start) = Concentration _(final) x Volume _(final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

Serial Dilutions
Concertration (start):
Dilution-folds:

Computed Result

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
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C8=C7/X	C8:	LOG(C8):

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

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

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01598571	Completed	Drug: Fostamatinib	Healthy	AstraZeneca	May 2012	Phase 1
NCT01387308	Completed	Drug: Fostamatinib	Healthy	AstraZeneca	August 2011	Phase 1
NCT01336218	Completed	Drug: fostamatinib\|Drug: rifampicin	Rheumatoid Arthritis\|Healthy Volunteers	AstraZeneca	April 2011	Phase 1
NCT01222455	Completed	Drug: Fostamatinib	Hepatic Impairment\|Healthy Volunteers\|Pharmacokinetics\|Amount of R406 in Blood	AstraZeneca	October 2010	Phase 1

Tech Support

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

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Frequently Asked Questions

Question 1:
What’s the difference between S1533 and S2194?
Answer:
S1533 and S2194 are two different forms of R406. S1533 is the free base form, containing only R406 molecule without a acid added to it. S2194 has an additional C6H6O3S acid on it which makes the molecule a salt form. The free base and salt forms have same biology activities. Free base has a lower molecular weight and salt form has a better solubility in DMSO.

Syk Signaling Pathway Map

Syk Inhibitors with Unique Features

Most Potent Syk Inhibitor

PRT062607 (P505-15, BIIB057) HCl : Syk, IC50=1 nM.
Syk Inhibitor in Clinical Trial

Fostamatinib (R788) : Phase III for Rheumatoid Arthritis.
Newest Syk Inhibitor

PRT062607 (P505-15, BIIB057) HCl : Novel, highly selective Syk inhibitor with IC50 of 1 nM, >80-fold selective for Syk than Fgr, Lyn, FAK, Pyk2 and Zap70.
Classic Syk Inhibitor

R406 (free base) : Syk inhibitor with IC50 of 41 nM, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. Phase 2.

Related Syk Products

PX-478 2HCl ^New

PX-478 2HCl is an orally active, and selective hypoxia-inducible factor-1α (HIF-1α) inhibitor. PX-478 2HCl induces apoptosis and has anti-tumor activity. Phase 1.
Defactinib (VS-6063) ^New

Defactinib (VS-6063, PF-04554878) is a selective, and orally active FAK inhibitor. Phase 2.
SU6656 ^New

SU 6656 is a selective Src family kinase inhibitor with IC50 of 280 nM, 20 nM, 130 nM, and 170 nM for Src, Yes, Lyn, and Fyn, respectively.
R406 (free base)

R406 (free base) is a potent Syk inhibitor with IC50 of 41 nM in a cell-free assay, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. R406 (free base) triggers apoptosis. Phase 1.
Fostamatinib (R788) disodium

Fostamatinib disodium (R788, Tamatinib Fosdium), a prodrug of the active metabolite R406, is a Syk inhibitor with IC50 of 41 nM in a cell-free assay, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. Phase 3.

Features:Clinically used oral formulation of R406.
Fostamatinib (R788)

Fostamatinib (R788), a prodrug of the active metabolite R406, is a Syk inhibitor with IC50 of 41 nM, strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. Phase 3.

Features:Converted into its active metabolite R406 in vivo.
Piceatannol

Piceatannol, a natural stilbene, is a selective Syk inhibitor and ~10-fold selectivity versus Lyn.
PRT062607 (P505-15) HCl

PRT062607 (P505-15, BIIB057, PRT-2607) HCl is a novel, highly selective Syk inhibitor with IC50 of 1 nM in cell-free assays, >80-fold selective for Syk than Fgr, PAK5, Lyn, FAK, Pyk2, FLT3, MLK1 and Zap70.
Entospletinib (GS-9973)

Entospletinib (GS-9973) is an orally bioavailable, selective Syk inhibitor with IC50 of 7.7 nM in a cell-free assay and showed 13- to >1000-fold cellular selectivity for Syk over other kinases(including Jak2, ckit, Flt3, Ret, KDR) as assessed by target protein phosphorylation or functional response.
Ibrutinib (PCI-32765)

Ibrutinib (PCI-32765) is a potent and highly selective Brutons tyrosine kinase (Btk) inhibitor with IC50 of 0.5 nM in cell-free assays, modestly potent to Bmx, CSK, FGR, BRK, HCK, less potent to EGFR, Yes, ErbB2, JAK3, etc. Ibrutinib is applicable as a Btk ligand in the synthesis of a series of PROTACs including P13I.

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R406