product name R406
Description: R406 is a potent Syk inhibitor with IC50 of 41 nM in cell-free assays, it strongly inhibits Syk but not Lyn, 5-fold less potent to Flt3. R406 impairs platelet activation and monocyte tissue factor expression triggered by heparin-PF4 complex directed antibodies. R406 blocks fc receptor signaling and reduces immune complex-mediated inflammation. R406 inhibited phosphorylation of Syk substrate linker for activation of T cells in mast cells and B-cell linker protein/SLP65 in B cells.
References: J Pharmacol Exp Ther. 2006 Dec;319(3):998-1008; Blood. 2009 Jul 30;114(5):1029-37.
628.63
Formula
C22H23FN6O5.C6H6O3S
CAS No.
841290-81-1
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 126 mg/mL (200.4 mM)
Water: <1 mg/mL
Ethanol: 8 mg/mL (12.7 mM)
Solubility (In vivo)
30% PEG400+0.5% Tween80+5% Propylene glycol: 30 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19420997
| In Vitro |
In vitro activity: 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. 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. R406 is a potent inhibitor of platelet signaling and functions initiated by FcγRIIA cross-linking by specific antibodies or by sera from HIT patients. Kinase Assay: Cell Assay: |
|---|---|
| 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. R406 does not adversely affect macrophage or neutrophil function in innate immune responses and has minimal functional immunotoxicity notwithstanding its lymphocytopenic effect. |
| Animal model | Arthritis is induced in C57BL/6 mice by intraperitoneal injection of 150 μL of pooled sera from adult K/BxN mice. |
| Formulation & Dosage | Formulated in 35% TPGS, 60% PEG 400, and 5% propylene glycol; 1, 5 mg/kg; Oral gavage |
| References | J Pharmacol Exp Ther. 2006 Dec;319(3):998-1008; Blood. 2009 Jul 30;114(5):1029-37. doi: 10.1182/blood-2009-03-212837. |
