841290-80-0 Usage
Description
R-406, also known as a Syk inhibitor, is a potent ATP-competitive inhibitor of spleen tyrosine kinase (Syk) with a Ki value of 30 nM. It is an intermediate used in the preparation of prodrugs of pyrimidine-2,4-diamines as anticancer agents. R-406 is orally available and has the ability to reduce immune complex-mediated inflammation.
Uses
Used in Anticancer Applications:
R-406 is used as an anticancer agent for cancers characterized by over-expression of Syk. It prevents signaling downstream of Syk and induces apoptosis, making it a promising candidate for cancer treatment.
Used in Autoimmune Disease Treatment:
R-406 is used as a therapeutic intervention in rheumatoid arthritis. It inhibits Syk-dependent signaling through c-Jun N-terminal kinase in rheumatoid arthritis synoviocytes, suggesting its potential use in treating this autoimmune disease.
Used in Immunology Research:
R-406 is used as a research tool to study the role of Syk in immune cell activation and immune complex-mediated inflammation. It blocks FcεRI-dependent mast cell activation with an EC50 value of 43 nM and reduces the release of IL-10, -12, and -13 by immune complex-pulsed dendritic cells at 3 μM.
Used in Drug Development:
R-406 is used as an intermediate in the preparation of prodrugs of pyrimidine-2,4-diamines, which are potential anticancer agents. Its use in drug development can lead to the discovery of new and effective cancer treatments.
Biological Activity
r406 is a potent syk inhibitorspleen tyrosine kinase (syk) is a non-receptor tyrosine kinase mainly expressed in hematopoietic cells. it transmits signals from a variety of cell surface receptors including cd74, fc receptor and integrins. it is crucial for adaptive immune response, and also very important for cellular adhesion, innate immune recognition, osteoclast maturation, platelet activation and vascular development. [1]functional abnormality of syk has been implicated in several blood malignancies. constitutively active syk can transform b cells. syk inhibition can be beneficial for patients with blood cancers and autoimmune diseases.r406 is a potent inhibitor of ige and igg mediated fc receptor activation with ec50 for degranulation of 56-64 nm. [2] r406 targets syk and inhibits phosphorylation of syk substrates by binding to its atp binding pocket and competing with atp. r406 strongly inhibits syk kinase activity with an ic50 of 41 nm.r406 induces apoptosis in diffuse large b-cell lymphoma cell lines. it blocks b cell receptor signaling through inhibiton of syk autophosphorylation of y525/y526 and syk-dependent phosphorylation of the b-cell linker protein. [3]r406 can be administrated orally.
references
[1]mocsai a, ruland j, tybulewicz vl. the syk tyrosine kinase: a crucial player in diverse biological functions. nat rev immunol 2010. 10(6): 387-402.[2]braselmann s, taylor v, zhao h, 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. 319(3): 998-1008.[3]chen l, monti s, juszczynski p, et al. syk-dependent tonic b-cell receptor signaling is a rational treatment target in diffuse large b-cell lymphoma. blood 2008. 111(4): 2230*2237.
Check Digit Verification of cas no
The CAS Registry Mumber 841290-80-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,4,1,2,9 and 0 respectively; the second part has 2 digits, 8 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 841290-80:
(8*8)+(7*4)+(6*1)+(5*2)+(4*9)+(3*0)+(2*8)+(1*0)=160
160 % 10 = 0
So 841290-80-0 is a valid CAS Registry Number.
841290-80-0Relevant articles and documents
Pharmaceutical Process and Intermediates
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Paragraph 0149; 0150; 0151; 0152, (2015/07/02)
The present disclosure provides for processes and intermediates in the large-scale manufacture of the compound of formula (I) or hydrates thereof.
2,4-PYRIMIDINEDIAMINE COMPOUNDS FOR USE IN THE TREATMENT OR PREVENTION OF AUTOIMMUNE DISEASES
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Page/Page column 70; 123, (2010/02/10)
The present invention provides methods of treating or preventing autoimmune diseases with 2,4-pyrimidinediamine compounds, as well as methods of treating, preventing or ameliorating symptoms associated with such diseases. Specific examples of autoimmune diseases that can be treated or prevented with the compounds include rheumatoid arthritis and/or its associated symptoms, systemic lups erythematosis and/or its associated symptoms and multiple sclerosis and/or its associated symptoms.
