Tamatinib besylate
featured

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 406779

CAS#: 841290-81-1 (besylate)

Description: Tamatinib, also known as R-406, is a potent inhibitor of Syk with IC50 of 41 nM. 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. R406 bound to the ATP binding pocket of Syk and inhibited its kinase activity as an ATP-competitive inhibitor (K(i) = 30 nM). R406 blocked Syk-dependent FcR-mediated activation of monocytes/macrophages and neutrophils and BCR-mediated activation of B lymphocytes. (last updated: 6/29/2016)


Price and Availability

Size
Price

5mg
USD 300
Size
Price

10mg
USD 500
Size
Price

25mg
USD 980

Tamatinib besylate, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.


Chemical Structure

img

Theoretical Analysis

MedKoo Cat#: 406779
Name: Tamatinib besylate
CAS#: 841290-81-1 (besylate)
Chemical Formula: C28H29FN6O8S
Exact Mass:
Molecular Weight: 628.6324
Elemental Analysis: C, 53.50; H, 4.65; F, 3.02; N, 13.37; O, 20.36; S, 5.10


Related CAS #: 841290-81-1 (besylate)   841290-80-0 (free base)    

Synonym: R406; R406; R406; R406; R406 besylate; R406 benzenesulfonate; Tamatinib,

IUPAC/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 benzenesulfonate

InChi Key: UXDRJPYSTZHIOE-UHFFFAOYSA-N

InChi Code: InChI=1S/C22H23FN6O5.C6H6O3S/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;7-10(8,9)6-4-2-1-3-5-6/h6-10H,1-5H3,(H3,24,25,26,27,28,29,30);1-5H,(H,7,8,9)

SMILES Code: 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


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO, not in water

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


References

1: Rolf MG, Curwen JO, Veldman-Jones M, Eberlein C, Wang J, Harmer A, Hellawell CJ, Braddock M. In vitro pharmacological profiling of R406 identifies molecular targets underlying the clinical effects of fostamatinib. Pharmacol Res Perspect. 2015 Oct;3(5):e00175. doi: 10.1002/prp2.175. Epub 2015 Sep 4. PubMed PMID: 26516587; PubMed Central PMCID: PMC4618646.

2: Borge M, Remes Lenicov F, Nannini PR, de los Ríos Alicandú MM, Podaza E, Ceballos A, Fernández Grecco H, Cabrejo M, Bezares RF, Morande PE, Oppezzo P, Giordano M, Gamberale R. The expression of sphingosine-1 phosphate receptor-1 in chronic lymphocytic leukemia cells is impaired by tumor microenvironmental signals and enhanced by piceatannol and R406. J Immunol. 2014 Sep 15;193(6):3165-74. doi: 10.4049/jimmunol.1400547. Epub 2014 Aug 15. PubMed PMID: 25127862.

3: Pritchard EM, Stewart E, Zhu F, Bradley C, Griffiths L, Yang L, Suryadevara PK, Zhang J, Freeman BB 3rd, Guy RK, Dyer MA. Pharmacokinetics and efficacy of the spleen tyrosine kinase inhibitor r406 after ocular delivery for retinoblastoma. Pharm Res. 2014 Nov;31(11):3060-72. doi: 10.1007/s11095-014-1399-y. Epub 2014 Jun 7. PubMed PMID: 24906597; PubMed Central PMCID: PMC4213378.

4: Lhermusier T, van Rottem J, Garcia C, Xuereb JM, Ragab A, Martin V, Gratacap MP, Sié P, Payrastre B. The Syk-kinase inhibitor R406 impairs platelet activation and monocyte tissue factor expression triggered by heparin-PF4 complex directed antibodies. J Thromb Haemost. 2011 Oct;9(10):2067-76. doi: 10.1111/j.1538-7836.2011.04470.x. PubMed PMID: 21848694.

5: Sweeny DJ, Li W, Grossbard E, Lau DT. Contribution of gut bacteria to the metabolism of the spleen tyrosine kinase (Syk) inhibitor R406 in cynomolgus monkey. Xenobiotica. 2010 Jun;40(6):415-23. doi: 10.3109/00498251003734244. PubMed PMID: 20415544.

6: Sweeny DJ, Li W, Clough J, Bhamidipati S, Singh R, Park G, Baluom M, Grossbard E, Lau DT. Metabolism of fostamatinib, the oral methylene phosphate prodrug of the spleen tyrosine kinase inhibitor R406 in humans: contribution of hepatic and gut bacterial processes to the overall biotransformation. Drug Metab Dispos. 2010 Jul;38(7):1166-76. doi: 10.1124/dmd.110.032151. Epub 2010 Apr 6. PubMed PMID: 20371637.

7: Quiroga MP, Balakrishnan K, Kurtova AV, Sivina M, Keating MJ, Wierda WG, Gandhi V, Burger JA. B-cell antigen receptor signaling enhances chronic lymphocytic leukemia cell migration and survival: specific targeting with a novel spleen tyrosine kinase inhibitor, R406. Blood. 2009 Jul 30;114(5):1029-37. doi: 10.1182/blood-2009-03-212837. Epub 2009 Jun 2. PubMed PMID: 19491390.

8: Spalton JC, Mori J, Pollitt AY, Hughes CE, Eble JA, Watson SP. The novel Syk inhibitor R406 reveals mechanistic differences in the initiation of GPVI and CLEC-2 signaling in platelets. J Thromb Haemost. 2009 Jul;7(7):1192-9. doi: 10.1111/j.1538-7836.2009.03451.x. Epub 2009 Apr 24. PubMed PMID: 19422460.

9: Zhu Y, Herlaar E, Masuda ES, Burleson GR, Nelson AJ, Grossbard EB, Clemens GR. Immunotoxicity assessment for the novel Spleen tyrosine kinase inhibitor R406. Toxicol Appl Pharmacol. 2007 Jun 15;221(3):268-77. Epub 2007 Mar 31. PubMed PMID: 17490694.

10: Braselmann S, Taylor V, Zhao H, Wang S, Sylvain C, Baluom M, Qu K, Herlaar E, Lau A, Young C, Wong BR, Lovell S, Sun T, Park G, Argade A, Jurcevic S, Pine P, Singh R, Grossbard EB, Payan DG, Masuda ES. 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. Epub 2006 Aug 31. Erratum in: J Pharmacol Exp Ther. 2013 May;345(2):326. PubMed PMID: 16946104.