R406 free base

SKU: orb1305445

Description

R406 free base is a selective and potent inhibitor of spleen tyrosine kinase (Syk). It is widely used in biochemical and cellular research to investigate Syk-dependent signaling pathways in immunology and oncology, with applications in both in vitro assays and in vivo disease models.

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 841290-80-0
• MW: 470.45
• Purity: 99.31%
• Formula: C₂₂H₂₃FN₆O₅
• SMILES: COc1cc(Nc2ncc(F)c(Nc3ccc4OC(C)(C)C(=O)Nc4n3)n2)cc(OC)c1OC
• Target: Apoptosis,FLT,Syk
• Solubility: DMSO:4.71 mg/mL (10.01 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  Syk:41 nM
• In Vivo:
  Treatment with R406 at concentrations of 1 μM or 4 μM induces caspase 9 and 3 activation in DLBCL cell lines, leading to significant cell apoptosis without activating caspase 8. R406 selectively inhibits the Syk-dependent signaling pathways in various cells, demonstrating superior efficacy with EC50 values ranging from 33 nM to 171 nM compared to its effect on Syk-independent pathways. It effectively inhibits cell proliferation in diffuse large B-cell lymphoma (DLBCL) cell lines, with EC50 values between 0.8 μM to 8.1 μM. Pre-treatment with R406 completely blocks phosphorylation of SYK525/526 and SYK-dependent phosphorylation of BLNK post B-cell receptor (BCR) cross-linking in R406-sensitive DLBCL. Additionally, after 24 and 48 hours of R406 treatment, MMP-9 mRNA levels significantly reduced by 2.8 and 4.3 times, respectively, compared to control groups, thereby decreasing the invasiveness of RL cells.
• In Vitro:
  Oral administration of R406 to mice with immune complex-induced inflammatory responses significantly inhibited the cutaneous reverse passive Arthus reaction, with treatments at 1 mg/kg and 5 mg/kg yielding suppression rates of 72% and 86% respectively, compared to the control group. Furthermore, treatment with 10 mg/kg R406 in mice pre-treated with collagen antibodies markedly reduced inflammation and swelling, diminished progressive arthritis to a lower level, and delayed the onset in the K/BxN serum transfer mouse model, reducing clinical arthritis severity by 50%.
• Cell Research:
  DLBCL cell lines are treated with serial dilutions of R406 (0.3, 0.6, 1.25, 2.5, or 5 μM) for 72 or 96 hours. Thereafter, cellular proliferation is determined by MTT assay, and cell apoptosis is assessed by using annexin V–FITC/propidium iodide (PI) staining. For the determination of caspase 9, 8, and 3, cells are lysed, size-fractionated by polyacrylamide gel electrophoresis (PAGE), and immunoblotted. (Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Inhibitor, inhibit, FLT3, Fms like tyrosine kinase 3, Apoptosis, Cluster of differentiation antigen 135, CD135, Spleen tyrosine kinase, Syk, R406, R-406, R406 (free base), R406 free base, R-406 free base, R 406

Compound Identifiers

PubChem CID

11213558