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Purity: ≥98%
Tamatinib (formerly known as R406) is a novel potent and ATP competitive Syk inhibitor with potential to treat immune disorders and inflammatory conditions. It inhibits Syk with an IC50 of 41 nM in cell-free assays, and strongly inhibits Syk but not Lyn, shows 5-fold less potency against Flt3. Tamatinib exhibited high efficacy in a number of animal models of immune disorders such as anticollagen antibody-induced arthritis.
| ln Vitro |
Adenosine transporter (IC50=1.84 µM), monoamine transporter (IC50=2.74 µM), and adenosine A3 receptor (IC50=0.081 µM) are all inhibited by R406[1]. Huh7 hepatocyte, A549 epithelial, and H1299 lung cancer lines are all inhibited by R406, with corresponding EC50s of 15.1, 2.9, and 6.3 µM[1]. R406 prevents mast cell phosphorylation of the Syk substrate LAT and B cell phosphorylation of BLNK/SLP65[1].
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| ln Vivo |
R406 (5 and 10 mg/kg) is effective in lowering clinical symptoms and improving the Arthus reaction in the K/BxN and collagen antibody-induced arthritis (CAIA) models of rheumatoid arthritis (RA). R406 inhibits Fc receptor signaling, which reduces immune complex (IC)-mediated inflammation[1].
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: Cultured human mast cells (CHMC) Tested Concentrations: 0.016, 0.08, 0.4, 2 µM Incubation Duration: 40 minutes Experimental Results: Inhibited all other kinases tested at 5 to 100 fold less potency than Syk as judged by phosphorylation of target proteins. |
| Animal Protocol |
Animal/Disease Models: Female balb/c (Bagg ALBino) mouse (6-8 weeks) with CAIA[1]
Doses: 5 and 10 mg/kg Route of Administration: Administered orally, bid , for 14 days, starting 4 hrs (hours) after antibody challenge on day 0. Experimental Results: decreased inflammation and swelling, and the arthritis progressed more slowly in animals treated than in vehicle controls. Animal/Disease Models: Female C57BL/6 mice with arthritis[1] Doses: 10 mg/kg Route of Administration: Administered orally one hour before serum injection; bid; for 13 days Experimental Results: Delayed the onset and decreased the severity of clinical arthritis. Paw thickening and clinical arthritis were decreased by approximately 50%. |
| References |
[1]. Sylvia Braselmann, et al. R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation. J Pharmacol Exp Ther. 2006 Dec;319(3):998-1008.
[2]. Hoon-Suk Cha , et al. A novel spleen tyrosine kinase inhibitor blocks c-Jun N-terminal kinase-mediated gene expression in synoviocytes. J Pharmacol Exp Ther. 2006 May;317(2):571-8. |
| Molecular Formula |
C22H23FN6O5
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|---|---|
| Molecular Weight |
470.45
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| CAS # |
841290-80-0
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| Related CAS # |
R406;841290-81-1
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| SMILES |
O=C1NC2=NC(NC3=NC(NC4=CC(OC)=C(OC)C(OC)=C4)=NC=C3F)=CC=C2OC1(C)C
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| InChi Key |
NHHQJBCNYHBUSI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H23FN6O5/c1-22(2)20(30)28-19-13(34-22)6-7-16(27-19)26-18-12(23)10-24-21(29-18)25-11-8-14(31-3)17(33-5)15(9-11)32-4/h6-10H,1-5H3,(H3,24,25,26,27,28,29,30)
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| Chemical Name |
6-((5-fluoro-2-((3,4,5-trimethoxyphenyl)amino)pyrimidin-4-yl)amino)-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one
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| Synonyms |
R406 besylate; R406 benzenesulfonate; Tamatinib; R 406, R406, R-406;
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1256 mL | 10.6281 mL | 21.2562 mL | |
| 5 mM | 0.4251 mL | 2.1256 mL | 4.2512 mL | |
| 10 mM | 0.2126 mL | 1.0628 mL | 2.1256 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00326339 | Completed | Drug: R788 Drug: Placebo |
Rheumatoid Arthritis | Rigel Pharmaceuticals | August 2006 | Phase 2 |
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The Syk inhibitor R406 induces CLL cell apoptosis and abrogates BCR-derived survival signals. Blood. 2009 Jul 30; 114(5): 1029–1037. |
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