R406

For research use only.

Catalog No.S2194

72 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 72 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 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=>
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Wsu-NHL NVjqN3B1TnWwY4Tpc44hSXO|YYm= NF:yOWo1KM7:TR?= M2HUR|E3KGh? MkK1bY5pcWKrdIOgeI9vcWNiQlzOT{B1gXKxc3nu[UBxcG:|cHjvdplt[XSrb36= MkTtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOThyME[2PVYoRjF6MEC2Olk3RC:jPh?=
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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+
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A673 NVLYTYN5eUiWUzDhd5NigQ>? NHvmXmlyUFSVIH;mJJBm\GmjdILpZ{Bk[W6lZYKgZ4VtdCCuaX7ld{B1dyCrZHXueIlngSCvdXz0bZBt\SCxcIDvdpR2dmm2aXXzJIZweiCmcoXnJJJmeHW{cH;zbY5oQiCScnntZZJ6KHOlcnXlckBnd3JiQU[3N{Bk\Wyucx?= MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zQTR|NUGzPUc,Ojl2M{WxN|k9N2F-
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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     


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
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

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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