R406 free base

SKU: orb1223887

Description

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. Phase 1.

Key Properties

• CAS Number: 841290-80-0
• MW: 470.45
• Purity: >98% (HPLC)
• Formula: C₂₂H₂₃FN₆O₅
• SMILES: COC1=CC(NC2=NC=C(F)C(NC3=NC4=C(OC(C)(C)C(=O)N4)C=C3)=N2)=CC(OC)=C1OC
• Target: Syk
• Solubility: DMSO: 21 mg/mL (44.63 mM)

Bioactivity

• In Vivo:
  R406 (5 and 10 mg/kg) shows efficacy in the amelioration of the Arthus reaction and in reducing clinical symptoms in the collagen antibody-induced arthritis (CAIA) and K/BxN models of rheumatoid arthritis (RA). Immune complex (IC)-mediated inflammation is reduced by inhibition of Fc receptor signaling with R406. Animal model: Female Balb/c mice (6-8 weeks) with CAIA. Dosage: 5 and 10 mg/kg. Administration: Administered orally, b. i. d, for 14 days, starting 4 hours after antibody challenge on day 0. Result: Reduced inflammation and swelling, and the arthritis progressed more slowly in treated animals than in vehicle controls. Animal model: Female C57BL/6 mice with arthritis. Dosage: 10 mg/kg. Administration: Administered orally one hour before serum injection; b. i. d; for 13 days. Result: Delayed the onset and reduced the severity of clinical arthritis. Paw thickening and clinical arthritis were reduced by approximately 50%.
• In Vitro:
  R406 inhibits adenosine A3 receptor (IC50 = 0.081 μM), adenosine transporter (IC50 = 1.84 μM), and monoamine transporter (IC50 = 2.74 μM). R406 inhibits Huh7 hepatocyte, A549 epithelial, and H1299 lung cancer lines with EC50s of 15.1, 2.9 and 6.3 μM, respectively. R406 inhibits phosphorylation of Syk substrate LAT in mast cells and BLNK/SLP65 in B cells. Western blot analysis. Cell line: Cultured human mast cells (CHMC. Concentration: 0.016, 0.08, 0.4, 2 μM Incubation time: 40 minutes. Result: Inhibited all other kinases tested at 5 to 100 fold less potency than Syk as judged by phosphorylation of target proteins.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

Syk