R406

For research use only.

Catalog No.S2194

63 publications

R406 Chemical Structure

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.

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Selleck's R406 has been cited by 63 publications

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 Ki 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-
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SK-M-MC NIDRSZVHfW6ldHnvckBie3OjeR?= M2DsWFEhcHJ? MoHlTY5pcWKrdHnvckBw\iCUZYSgbY4hcHWvYX6gV2suVS2PQzDj[YxteyCjc4Pld5Nm\CCjczDhd5Nme3OnZDDhd{BxcG:|cHjvdplt[XSrb36gZYZ1\XJiMTDodkBqdmO3YnH0bY9vNCCHQ{WwQVAvODN4zszNMi=> NYX2eYtWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS3O|k2OTRpPkK0O|c6PTF2PD;hQi=>
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mesangial cells MoTMSpVv[3Srb36gZZN{[Xl? M2e1[GlvcGmkaYTpc44hd2ZiU2nLJIlvKGO3bIT1doVlKGi3bXHuJI1me2GwZ3nhcEBk\WyuczDhd5Nme3OnZDDhd{Bz\WS3Y4Tpc44hcW5iRnPldJNqdG:wUkGvSoNo[W2vYWKtcYVlcWG2ZXSgd4lodmGuaX7nJJJme3CxboPld{whTUN3ME2wMlA2Ps7:TT6= NWfsR|hORGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkKyOVczOTNpPkKyNlU4OjF|PD;hQi=>
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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     


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     


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     


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     


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     


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     


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)

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

Molecular Weight 628.63
Formula

C22H23FN6O5.C6H6O3S

CAS No. 841290-81-1
Storage powder
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

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% DMSO % % Tween 80 % ddH2O
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Clinical Trial Information

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

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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

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID