R406

Name: R406
Brand: Selleck Chemicals
SKU: S2194
Rating: 5 (63 reviews)

For research use only.

Catalog No.S2194

63 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 63 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 )

Cell Rep, 2021, 34(11):108870

PubMed: 33730585 ( 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 )

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 )

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 )
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	MWTGeY5kfGmxbjDBd5NigQ>?	MofQNUDPxE1?	NXPLfW1bO8LiaB?=		Mlm4doVlfWOnczDtbYdz[XSrb39CpC=>	NY\mWJFKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[yOVE4PjFpPkK2NlUyPzZzPD;hQi=>
U266	MUnGeY5kfGmxbjDBd5NigQ>?	NVHKUnpGOSEQvF2=	MYWzxsBp		NU\ZNpd6emWmdXPld{BucWe{YYTpc47DqA>?	NWSydYlMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[yOVE4PjFpPkK2NlUyPzZzPD;hQi=>
Jeko-1	NWLob25JT3Kxd4ToJGlvcGmkaYTpc44hSXO\|YYm=		M4n5ZVQ5KGh?		NWSxfGd6UUN3ME21MlA3QDJ4IN88US=>	MlrRQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV6M{W3OVUoRjJ3OEO1O\|U2RC:jPh?=
Mino	M4HPRmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7		M1HzPVQ5KGh?		MnXETWM2OD13LkewPFU1KM7:TR?=	MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTh\|NUe1OUc,OjV6M{W3OVU9N2F-
Jeko-1	MoHSRZBweHSxc3nzJGF{e2G7	NUmzdItCPcLizszN	MY[yOEBp		NF\0ZXRqdmS3Y3XzJFI2NjIEoNMxxsA{NjMEoDWgZZBweHSxc3nz	NVzkRm1sRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkW4N\|U4PTVpPkK1PFM2PzV3PD;hQi=>
primary MCL	NXXDcmlVSXCxcITvd4l{KEG\|c3H5	NGry[3MzKML3TR?=	MlL4NlQhcA>?		MU\pcoNz\WG\|ZYOgd4lodmmoaXPhcpRtgSCjcH;weI9{cXQEoB?=	NHPFOo09[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUO4PFM4Oyd-MkWzPFg{PzN:L3G+
PBMCs	M{XnN2NmdGxiVnnhZoltcXS7IFHzd4F6	Mn3XNE02OCEQvF2=	NF\kW4czPCCq	Mof6SG1UVw>?	MnWybY5pcWKrdIOgZ4VtdCC4aXHibYxqfHliZH;z[UBl\XCnbnTlcpRtgQ>?	NHrHdHk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUGyO\|g3Oid-MkWxNlc5PjJ:L3G+
PBMCs	NVfV[VlFTnWwY4Tpc44hSXO\|YYm=	M3X3VFUh\|ryP	M{fET\|EhcA>?	NEP0OlVFVVOR	NXXuN3M2\GWlcnXhd4V{KHSqZTDj[YxtKG2rZ4LheIlwdg>?	NHuwW2c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUGyO\|g3Oid-MkWxNlc5PjJ:L3G+
CFSE-CD4+ T	M4rKZ2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7	M3j3d\|AvODZ{NT2xJO69VQ>?	NGfSPWo1KGR?		MXzicI9kc3NicILvcIln\XKjdHnvckBw\iCJVljEMYRmemm4ZXSgR2Q1M8LiVDDj[YxteyCjbnSgR2QyOWJtwrDj[Yxtew>?	NY\OOmVvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS2O\|k6QDJpPkK0Olc6QTh{PD;hQi=>
CFSE-CD11b+	M3HHfGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7	MkHiNE4xPjJ3LUGg{txO	MknDPEBl		M{W2W4Jtd2OtczDwdo9tcW[ncnH0bY9vKG:oIFfWTGQu\GW{aY\l[EBETDRtwrDUJINmdGy\|IHHu[EBETDFzYjxCpINmdGy\|	NVLBfmxDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS2O\|k6QDJpPkK0Olc6QTh{PD;hQi=>
HMECs	NWT4ZZNvTnWwY4Tpc44hSXO\|YYm=	MkTPNE0yOCEQvF2=	NVrSdXJ3OjBibXnu		MX;pcohq[mm2czDWSWdHNXO2aX31cIF1\WRicnXs[YF{\SCxZjDOUy=>	M3LxWVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2M{K5OVQ1Lz5{NEOyPVU1PDxxYU6=
AB5	MnLHRZBweHSxc3nzJGF{e2G7	Mn\mNE0zNjVizszN	MUO0PEBp	MlOzSG1UVw>?	NF7QZlVqdmS3Y3XzJIFxd3C2b4Ppdy=>	Mnz1QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN\|OUi5NVEoRjJ\|M{m4PVEyRC:jPh?=
JB7	M{W4WGFxd3C2b4Ppd{BCe3OjeR?=	NXLOPVFWOC1{LkWg{txO	NFTD[pM1QCCq	NH\TcWJFVVOR	M37MS4lv\HWlZYOgZZBweHSxc3nz	NG\vb3E9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{O5PFkyOSd-MkOzPVg6OTF:L3G+
AB5	NFvrXVBIem:5dHigTY5pcWKrdHnvckBCe3OjeR?=	MVGwMVIvPSEQvF2=	NGTNd4I1QCCq	M3TpPGROW09?	NUfkNlUxcW6mdXPld{Bk\WyuIHP5Z4xmKGG{cnXzeC=>	MkHmQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN\|OUi5NVEoRjJ\|M{m4PVEyRC:jPh?=
JB7	MYTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>?	NEftR4gxNTJwNTFOwG0>	M3;CUVQ5KGh?	NXPSc4ZMTE2VTx?=	MWLpcoR2[2W\|IHPlcIwh[3mlbHWgZZJz\XO2	MoX5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN\|OUi5NVEoRjJ\|M{m4PVEyRC:jPh?=
RL	M{jWTWZ2dmO2aX;uJGF{e2G7	NILwT\|MzNjVxNTFOwG0>	MUCyOE81QCCq	NUmycJV[TE2VTx?=	M{\hSIlv\HWlZYOgZUBxd3SnboSg[IVkemWjc3WgbY4hVU2SLUmgcXJPSSCneIDy[ZN{cW:w	MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl{Nkm2OUc,OjF7Mk[5OlU9N2F-
RL	M{GxSmZ2dmO2aX;uJGF{e2G7	Mo\uNU8zNjVizszN	MlPkNlQhcA>?	NVnI[po1TE2VTx?=	M4\ZUpJm\HWlZYOgeIhmKGGldHn2ZZRqd25ib3[gRYt1KGGwZDDwO\|BUPkt?	MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl{Nkm2OUc,OjF7Mk[5OlU9N2F-
platelet	NFjhOHRHfW6ldHnvckBCe3OjeR?=	M4rrbVHDqM7:bR?=	MYS1JI1qdg>?		MoLDbY5pcWKrdIOgSoPPu1KLSVGtcYVlcWG2ZXSgdIxifGWuZYSgZYdoemWpYYTpc44>	MXO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTh2OE[5OEc,OjF6NEi2PVQ9N2F-
platelet	MWnGeY5kfGmxbjDBd5NigQ>?	NEfDNFMxNjB3L{GvNk42KM7:TR?=	NW\CVIV4PSCvaX6=		Mn3abY5pcWKrdIOgeIhmKHOrZ37hcIlv\yCvZXPoZY5qe22\|IHTve45{fHKnYX2gc4YhTmQQs2LJTWE>	M{OzVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOES4Olk1Lz5{MUi0PFY6PDxxYU6=
DoHH2	MmnFRZBweHSxc3nzJGF{e2G7	MnTTNE8{NzFyIN88US=>	MoXsOFghcA>?		NHL0RoNqdmS3Y3XzJINmdGxiZHXheIghe2mpbnnmbYNidnSueR?=	NEHZO3M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MEi3OVQxQCd-MkC4O\|U1ODh:L3G+
Jeko-1	M1fpfWFxd3C2b4Ppd{BCe3OjeR?=	MXqwM\|MwOTBizszN	NU\EVpNqPDhiaB?=		NEDRdohqdmS3Y3XzJINmdGxiZHXheIghe2mpbnnmbYNidnSueR?=	MmfQQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB6N{W0NFgoRjJyOEe1OFA5RC:jPh?=
Raji	NUfZeYZoSXCxcITvd4l{KEG\|c3H5	NEW3VXExNzNxMUCg{txO	MVy0PEBp		MV\pcoR2[2W\|IHPlcIwh\GWjdHigd4lodmmoaXPhcpRtgQ>?	MkfxQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjB6N{W0NFgoRjJyOEe1OFA5RC:jPh?=
DHL4	MoK0RZBweHSxc3nzJGF{e2G7	M4[xWVAwOS92IN88US=>	MnzXPVYhcA>?		MnfObY5lfWOnczDhdI9xfG:\|aYOg[I9{\SCmZYDlcoRmdnSueR?=	M{TSW\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6MEC2Olk3Lz5zOECwOlY6PjxxYU6=
LY7	MljQRZBweHSxc3nzJGF{e2G7	M165flAwOS92IN88US=>	Mnq4PVYhcA>?		NWH6XWMycW6mdXPld{BieG:ydH;zbZMh\G:\|ZTDk[ZBmdmSnboTsfS=>	M1[2TlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6MEC2Olk3Lz5zOECwOlY6PjxxYU6=
LY3	NGewbY5CeG:ydH;zbZMhSXO\|YYm=	MlXONE8yNzRizszN	Mmn6PVYhcA>?		NFvlS\|hqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5	NEDQ[Jk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOECwOlY6Pid-MUiwNFY3QTZ:L3G+
DHL6	M3HNd2Fxd3C2b4Ppd{BCe3OjeR?=	MnvkNE8yNzRizszN	NW\xcI9TQTZiaB?=		MWDpcoR2[2W\|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7	NXuyT2x7RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUiwNFY3QTZpPkG4NFA3Pjl4PD;hQi=>
LY10	M3nTPWFxd3C2b4Ppd{BCe3OjeR?=	NHzjWXYxNzFxNDFOwG0>	NXLVXYtNQTZiaB?=		NFXzeHFqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5	MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDByNk[5Okc,OThyME[2PVY9N2F-
DHL10	NWi3WoFKSXCxcITvd4l{KEG\|c3H5	NE\xb5ExNzFxNDFOwG0>	MXe5OkBp		M2fwXIlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm=	MnfTQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyME[2PVYoRjF6MEC2Olk3RC:jPh?=
Wsu-NHL	MYjBdI9xfG:\|aYOgRZN{[Xl?	NYS5XmlYOC9zL{Sg{txO	MmHYPVYhcA>?		NFfLeVlqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5	MnXtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyME[2PVYoRjF6MEC2Olk3RC:jPh?=
LY18	MWfBdI9xfG:\|aYOgRZN{[Xl?	MYqwM\|EwPCEQvF2=	M2DLWlk3KGh?		M4fqWIlv\HWlZYOgZZBweHSxc3nzJIRwe2ViZHXw[Y5l\W62bIm=	MXy8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDByNk[5Okc,OThyME[2PVY9N2F-
LY1	MoHTRZBweHSxc3nzJGF{e2G7	MXywM\|EwPCEQvF2=	MnjwPVYhcA>?		NFLuNmZqdmS3Y3XzJIFxd3C2b4Ppd{Bld3OnIHTldIVv\GWwdHz5	MV68ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDByNk[5Okc,OThyME[2PVY9N2F-
DHL8	M1rpPGFxd3C2b4Ppd{BCe3OjeR?=	NHSzXFIxNzFxNDFOwG0>	NFjRNmw6PiCq		MXXpcoR2[2W\|IHHwc5B1d3OrczDkc5NmKGSncHXu[IVvfGy7	MkHlQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyME[2PVYoRjF6MEC2Olk3RC:jPh?=
DHL4	MmPhRZBweHSxc3nzJGF{e2G7	MWS0JO69VQ>?	Mn7uPVYhcA>?		M1Hs[Ilv\HWlZYOgZ4xm[X[jZ3Wgc4Yh[2G\|cHHz[ZMhQSCjbnSgN{wh[nW2IH7veEBk[XOyYYPlJFg>	MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDByNk[5Okc,OThyME[2PVY9N2F-
DHL6	MljERZBweHSxc3nzJGF{e2G7	MXu0JO69VQ>?	NHPlc3c6PiCq		M4DBeIlv\HWlZYOgZ4xm[X[jZ3Wgc4Yh[2G\|cHHz[ZMhQSCjbnSgN{wh[nW2IH7veEBk[XOyYYPlJFg>	M4D2d\|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6MEC2Olk3Lz5zOECwOlY6PjxxYU6=
LY3	MY\BdI9xfG:\|aYOgRZN{[Xl?	MnXDOEDPxE1?	M3PSVVk3KGh?		NF3Rd2FqdmS3Y3XzJINt\WG4YXflJI9nKGOjc4Dhd4V{KDliYX7kJFMtKGK3dDDuc5Qh[2G\|cHHz[UA5	M2HldVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF6MEC2Olk3Lz5zOECwOlY6PjxxYU6=
LY7	NGTt[XZCeG:ydH;zbZMhSXO\|YYm=	NHPXOVg1KM7:TR?=	NIDDdnc6PiCq		Mn3CbY5lfWOnczDjcIVifmGpZTDv[kBk[XOyYYPld{A6KGGwZDCzMEBjfXRibn;0JINie3Cjc3WgPC=>	MUO8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDByNk[5Okc,OThyME[2PVY9N2F-
DHL4	M{TvV2Z2dmO2aX;uJGF{e2G7	NIHyO2o1KM7:TR?=	M3v6XFE3KGh?		M4LZcIlvcGmkaYTzJJRwdmmlIFLMUmshfHm{b4PpcoUheGixc4Doc5J6dGG2aX;u	NI\nPVU9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOECwOlY6Pid-MUiwNFY3QTZ:L3G+
LY7	NXPXSolmTnWwY4Tpc44hSXO\|YYm=	MYm0JO69VQ>?	NYSyUJZyOTZiaB?=		MlXObY5pcWKrdIOgeI9vcWNiQlzOT{B1gXKxc3nu[UBxcG:\|cHjvdplt[XSrb36=	NFnORZQ9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOECwOlY6Pid-MUiwNFY3QTZ:L3G+
LY3	NFXUN5NHfW6ldHnvckBCe3OjeR?=	MYK0JO69VQ>?	MVixOkBp		MknjbY5pcWKrdIOgeI9vcWNiQlzOT{B1gXKxc3nu[UBxcG:\|cHjvdplt[XSrb36=	MnHFQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyME[2PVYoRjF6MEC2Olk3RC:jPh?=
DHL6	MoPJSpVv[3Srb36gRZN{[Xl?	MXW0JO69VQ>?	NUPxRlZ{OTZiaB?=		Mn7ibY5pcWKrdIOgeI9vcWNiQlzOT{B1gXKxc3nu[UBxcG:\|cHjvdplt[XSrb36=	NXPJ[4Q2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUiwNFY3QTZpPkG4NFA3Pjl4PD;hQi=>
LY10	NV62WYtnTnWwY4Tpc44hSXO\|YYm=	NYTIPWVLPCEQvF2=	MmHpNVYhcA>?		NGTWPGRqdmirYnn0d{B1d26rYzDCUG5MKHS7cn;zbY5mKHCqb4PwbI9zgWyjdHnvci=>	Mn\JQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyME[2PVYoRjF6MEC2Olk3RC:jPh?=
Wsu-NHL	NH;YR4pHfW6ldHnvckBCe3OjeR?=	NXzTVJNQPCEQvF2=	M1TKTlE3KGh?		M3fQSIlvcGmkaYTzJJRwdmmlIFLMUmshfHm{b4PpcoUheGixc4Doc5J6dGG2aX;u	MXS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yQDByNk[5Okc,OThyME[2PVY9N2F-
LY18	NUH0cZBXTnWwY4Tpc44hSXO\|YYm=	NVHLdJdYPCEQvF2=	MUKxOkBp		NFPxdZRqdmirYnn0d{B1d26rYzDCUG5MKHS7cn;zbY5mKHCqb4PwbI9zgWyjdHnvci=>	NH;kdFk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOECwOlY6Pid-MUiwNFY3QTZ:L3G+
MV411	MkTNSpVv[3Srb36gZZN{[Xl?		Mk\4O\|IhcHK\|		NXrQeYlLUW6qaXLpeIlwdiCxZjDGcJQ{KGmwIHj1cYFvKE2YNEGxJINmdGy\|IHHzd4V{e2WmIHHzJIF{e2W\|c3XkJIF{KHC{b3zp[oVz[XSrb36gZYZ1\XJiN{KgbJJ{KGmwY4XiZZRqd25iYomgd5Bm[3S{b4Doc5RwdWW2comsJGVEPTB;MD6wNe69VS5?	NGnGV3M9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe3PVUyPCd-MkS3O\|k2OTR:L3G+
TF1	M136fmZ2dmO2aX;uJIF{e2G7		MYGxJIhz		M1z0[mlvcGmkaYTpc44hd2ZiSnHrNkBqdiCncon0bJJweG:rZYTpck1{fGmvdXzheIVlKGi3bXHuJHRHOSClZXzsd{Bie3Onc4Pl[EBieyCjc4Pld5Nm\CCjczDwbI9{eGixLWP0ZZQ2KGGodHXyJFEhcHJiaX7jeYJifGmxbjygSWM2OD1yLkCxN:69VS5?	MorNQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR5N{m1NVQoRjJ2N{e5OVE1RC:jPh?=
neutrophils	NX;h[op1TnWwY4Tpc44h[XO\|YYm=				MkjTTY5pcWKrdHnvckBw\iCVWVugbY4hcHWvYX6gcoV2fHKxcHjpcJMh[2WubIOgZZN{\XO\|ZXSgZZMhemWmdXP0bY9vKGmwIF\j[ZB{cWyxbmKxM2Zk\2GvbXHSMY1m\GmjdHXkJJNq\26jbHnu[{Bz\XOyb37z[ZMtKEWFNUC9NE4xOzQQvF2u	NIDiSo49[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkK1O\|IyOyd-MkKyOVczOTN:L3G+
SK-M-MC	NIDRSZVHfW6ldHnvckBie3OjeR?=		M2DsWFEhcHJ?		MoHlTY5pcWKrdHnvckBw\iCUZYSgbY4hcHWvYX6gV2suVS2PQzDj[YxteyCjc4Pld5Nm\CCjczDhd5Nme3OnZDDhd{BxcG:\|cHjvdplt[XSrb36gZYZ1\XJiMTDodkBqdmO3YnH0bY9vNCCHQ{WwQVAvODN4zszNMi=>	NYX2eYtWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS3O\|k2OTRpPkK0O\|c6PTF2PD;hQi=>
mast cells	NEnJbJJHfW6ldHnvckBie3OjeR?=		NX;r[nJSOSCqch?=		MmTnTY5pcWKrdHnvckBw\iClS3n0JIlvKHO2ZX2gZ4VtdCCoYXP0c5Iue3SrbYXsZZRm\CCkb37lJI1ienKxdzDk[ZJqfmWmIH3veZNmKG2jc4SgZ4VtdHNiYYPz[ZN{\WRiYYOgdIhwe3Cqb4L5cIF1cW:wIHHmeIVzKDFiaIKgbY5kfWKjdHnvckwhTUN3ME2wMlA1Ps7:TT6=	MUC8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDd5OUWxOEc,OjR5N{m1NVQ9N2F-
B-cells	M{npcWZ2dmO2aX;uJIF{e2G7				MUTJcohq[mm2aX;uJI9nKFO\SzDpckBpfW2jbjDCMYNmdGy\|IHPlcIx{KGG\|c3Xzd4VlKGG\|IILl[JVkfGmxbjDpckBH[2Wyc3nsc45TOS:IY3fhcY1iWi2vZXTpZZRm\CC\|aXfuZYxqdmdicnXzdI9ve2W\|LDDFR\|UxRTBwMES4{txONg>?	MmLrQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjJ{NUeyNVMoRjJ{MkW3NlE{RC:jPh?=
Ramos	NW\mcVFTTnWwY4Tpc44h[XO\|YYm=				MXPJcohq[mm2aX;uJI9nKFO7azDpckBidnSraIXtZY4hUWePLYP0bY12dGG2ZXSgbJVu[W5iUnHtc5Mh[2WubIOgZZN{\XO\|ZXSgZZMh\GWlcnXhd4UhcW5iQlPSMY1m\GmjdHXkJGJNVkticHjvd5Bpd3K7bHH0bY9vKGK7IHPlcIx2dGG{IHHzd4F6NCCHQ{WwQVAvODV\|zszNMi=>	MVW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDd5OUWxOEc,OjR5N{m1NVQ9N2F-
mesangial cells	MoTMSpVv[3Srb36gZZN{[Xl?				M2e1[GlvcGmkaYTpc44hd2ZiU2nLJIlvKGO3bIT1doVlKGi3bXHuJI1me2GwZ3nhcEBk\WyuczDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5iRnPldJNqdG:wUkGvSoNo[W2vYWKtcYVlcWG2ZXSgd4lodmGuaX7nJJJme3CxboPld{whTUN3ME2wMlA2Ps7:TT6=	NWfsR\|hORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKyOVczOTNpPkKyNlU4OjF\|PD;hQi=>
SK-N-SH	M2jTO2Z2dmO2aX;uJIF{e2G7				NX;L[291UW6qaXLpeIlwdiCxZjDS[ZQhcW5iaIXtZY4hW0tvTj3TTEBk\WyuczygSWM2OD1yLkC4{txONg>?	NETZ[XA9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MkK1O\|IyOyd-MkKyOVczOTN:L3G+
mouse bone marrow cells	NVS3cZNyTnWwY4Tpc44h[XO\|YYm=				MlvkTY5pcWKrdHnvckBw\iCLTEOg[IVx\W6mZX70JJBzd2yrZnXyZZRqd25iaX6gR\|U4N0JzNjDtc5V{\SCkb37lJI1ienKxdzDj[YxteyC3c3nu[{BcO0ifdHj5cYllcW6nIHL5JIxqeXWrZDDzZ4lvfGmubHH0bY9vKGOxdX70bY5oNCCLQ{WwQVAvOTR5zszNMi=>	NUfLSYg5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS3NlY5ODZpPkK0O\|I3QDB4PD;hQi=>
B-cells	NF;TUFBHfW6ldHnvckBie3OjeR?=		NF3mdFAyKGi{		NI\TTXJKdmirYnn0bY9vKG:oIGP5b{BqdiCjbIDoZWloVS2\|dHnteYxifGWmIHj1cYFvKEJiY3XscJMh[XO\|ZYPz[YQh[XNiY3XscEBxem:uaX\ldoF1cW:wIHHmeIVzKDFiaIKgbY5kfWKjdHnvckBjgSCobH;3JIN6fG:vZYTyfUwhTUN3ME2wMlE2Oc7:TT6=	NILsUlM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NEe3PVUyPCd-MkS3O\|k2OTR:L3G+
THP1	NF7a[29HfW6ldHnvckBie3OjeR?=				MWDJcohq[mm2aX;uJI9nKFO\SzDpckBpfW2jbjDUTHAyKGOnbHzzJIF{e2W\|c3XkJIF{KHKnZIXjeIlwdiCrbjDGZ4Vxe2mub37SNU9H[2ejbX3hVk1u\WSrYYTl[EB{cWewYXzpcochemW\|cH;ud4V{NCCHQ{WwQVAvOTdzzszNMi=>	M1vjdlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ{MkW3NlE{Lz5{MkK1O\|IyOzxxYU6=
B-cells	M2fWTWZ2dmO2aX;uJIF{e2G7		NIfWflYyKGi{		NHS2eZpKdmirYnn0bY9vKG:oIGP5b{BqdiCjbIDoZWloVS2\|dHnteYxifGWmIHj1cYFvKEJiY3XscJMh[XO\|ZYPz[YQh[XNiQ1S4OkBmgHC{ZYPzbY9vKGGodHXyJFEhcHJiaX7jeYJifGmxbjDifUBndG:5IHP5eI9u\XS{eTygSWM2OD1yLkOzOe69VS5?	MlPWQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR5N{m1NVQoRjJ2N{e5OVE1RC:jPh?=
Ramos	Ml3JSpVv[3Srb36gZZN{[Xl?				NFzP[ZhKdmirYnn0bY9vKG:oIGP5b{BqdiCjboTpJGloVS2\|dHnteYxifGWmIHj1cYFvKFKjbX;zJINmdGy\|IHHzd4V{e2WmIHHzJGJNVkticHjvd5Bpd3K7bHH0bY9vKGK7IHPlcIx2dGG{IHHzd4F6NCCLQ{WwQVAvPDV5zszNMi=>	MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDd{NkiwOkc,OjR5Mk[4NFY9N2F-
Rec1	M3nQO2Z2dmO2aX;uJIF{e2G7	M3z3ZVIvPSC3TR?=	M1zyUlYhcHK\|		MlL0TY5pcWKrdHnvckBw\iCEVFugdIhwe3Cqb4L5cIF1cW:wIHnuJIh2dWGwIGLlZ\|Eh[2WubIOgZZQhOi53IIXNJIlv[3WkYYTl[EBnd3JiNjDodpMh[nliV3XzeIVzdiCkbH;0eIlv\yCvZYToc4Q>	NGLPeI89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUKyNlg4Pyd-MkWyNlI5Pzd:L3G+
Rec1	NYLkbGRLTnWwY4Tpc44h[XO\|YYm=	NFXmO4wzNjVidV2=	M2XPUVYhcHK\|		MXrJcohq[mm2aX;uJI9nKFO7azDwbI9{eGixconsZZRqd25iaX6gbJVu[W5iUnXjNUBk\WyuczDheEAzNjVidV2gbY5kfWKjdHXkJIZweiB4IHjyd{BjgSCZZYP0[ZJvKGKub4T0bY5oKG2ndHjv[C=>	M4HRUFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ3MkKyPFc4Lz5{NUKyNlg4PzxxYU6=
Rec1	M2G4UWZ2dmO2aX;uJIF{e2G7	NHK3Nm0zNjVidV2=	NXTqcFRiPiCqcoO=		M1LHfWlvcGmkaYTpc44hd2ZiTInuJJBpd3OyaH;yfYxifGmxbjDpckBpfW2jbjDS[YMyKGOnbHzzJIF1KDJwNTD1UUBqdmO3YnH0[YQh\m:{IE[gbJJ{KGK7IGfld5Rmem5iYnzveJRqdmdibXX0bI9l	MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTJ{Mki3O{c,OjV{MkK4O\|c9N2F-
SJ-GBM2	NHPkclRyUFSVIHHzd4F6				Ml;HdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFOMLVfCUVIh[2WubIO=	MlTtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
A673	MX7xTHRUKGG\|c3H5				NYLzcZNkeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IFG2O\|Mh[2WubIO=	M{e4WlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-MC	M3jLPJFJXFNiYYPzZZk>				MWfxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0tvTj3NR{Bk\Wyucx?=	MmW3QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
NB-EBc1	NEXzVHZyUFSVIHHzd4F6				NXz1dFY4eUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF7CMWVD[zFiY3XscJM>	MmP5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
Saos-2	M1LOSpFJXFNiYYPzZZk>				M3rC[5FJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCVYX;zMVIh[2WubIO=	MYW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-
OHS-50	M2T5cpFJXFNiYYPzZZk>				NYi5[4xCeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IF;IV{02OCClZXzsdy=>	NWraNYVzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh41	NV;Ue2VDeUiWUzDhd5NigQ>?				NEnXNpFyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiUni0NUBk\Wyucx?=	MXW8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR\|NUGzPUc,Ojl2M{WxN\|k9N2F-

... 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 (Different batches have different solubility ratios, please contact Selleck to provide you with the correct ratio)

% 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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C6=C5/X	C6:	LOG(C6):
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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 2021-01-06)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT01725230	Completed	Drug: Fostamatinib\|Drug: Rosuvastatin\|Drug: Simvastatin	Rheumatoid Arthritis	AstraZeneca	November 2012	Phase 1
NCT01598571	Completed	Drug: Fostamatinib	Healthy	AstraZeneca	May 2012	Phase 1
NCT01387308	Completed	Drug: Fostamatinib	Healthy	AstraZeneca	August 2011	Phase 1
NCT01355354	Completed	Drug: Digoxin\|Drug: Fostamatinib	Healthy Volunteers\|Rheumatoid Arthritis	AstraZeneca	June 2011	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.
R788 (Fostamatinib) Disodium

R788 (Fostamatinib) disodium (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