1446790-62-0 Usage
Biological Activity
ro9021 is a syk inhibitor.spleen tyrosine kinase (syk) is identified as a critical integrator of intracellular signals regulated by activated immunoreceptors, such as fc receptors and bcell receptors (bcr), which are of great importantance for the function and development of lymphoid cells.
in vitro
previous study found that in addition to the suppression of bcell receptor signaling in human peripheral blood mononuclear cells and whole blood, fcγr signaling in human monocytes, and fc r signaling in human mast cells, ro9021 could also block the in vitro osteoclastogenesis from mouse bone marrow macrophages. moreover, the toll-like receptor 9 signaling in human bcells could be blocked by ro9021, leading to the decreased levels of plasmablasts, immunoglobulin (ig) g and igm upon b-cell differentiation. in addition, ro9021 could also potently inhibit type i interferon production by human plasmacytoid dendritic cells (pdc) via tlr9 activation, and such effect was found to be specific to tlr9 since ro9021 did not show inhibitary effect on tlr4- or jak-stat-mediated signaling [1].
in vivo
animal study showed that the oral administration of ro9021could significanly inhibit the arthritis progression in the mcia model, with well observed pharmacokinetics-pharmacodynamic correlation [1].
IC 50
5.6 nm
references
[1] liao c, et al. selective inhibition of spleen tyrosine kinase (syk) with a novel orally bioavailable small molecule inhibitor, ro9021, impinges on various innate and adaptive immune responses: implications for syk inhibitors in autoimmune disease therapy. arthritis res ther. 2013 oct 4;15(5):r146.
Check Digit Verification of cas no
The CAS Registry Mumber 1446790-62-0 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,4,4,6,7,9 and 0 respectively; the second part has 2 digits, 6 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 1446790-62:
(9*1)+(8*4)+(7*4)+(6*6)+(5*7)+(4*9)+(3*0)+(2*6)+(1*2)=190
190 % 10 = 0
So 1446790-62-0 is a valid CAS Registry Number.
1446790-62-0Relevant articles and documents
Using ovality to predict nonmutagenic, orally efficacious pyridazine amides as cell specific spleen tyrosine kinase inhibitors
Lucas, Matthew C.,Bhagirath, Niala,Chiao, Eric,Goldstein, David M.,Hermann, Johannes C.,Hsu, Pei-Yuan,Kirchner, Stephan,Kennedy-Smith, Joshua J.,Kuglstatter, Andreas,Lukacs, Christine,Menke, John,Niu, Linghao,Padilla, Fernando,Peng, Ying,Polonchuk, Liudmila,Railkar, Aruna,Slade, Michelle,Soth, Michael,Xu, Daigen,Yadava, Preeti,Yee, Calvin,Zhou, Mingyan,Liao, Cheng
, p. 2683 - 2691 (2014/04/17)
Inhibition of spleen tyrosine kinase has attracted much attention as a mechanism for the treatment of cancers and autoimmune diseases such as asthma, rheumatoid arthritis, and systemic lupus erythematous. We report the structure-guided optimization of pyridazine amide spleen tyrosine kinase inhibitors. Early representatives of this scaffold were highly potent and selective but mutagenic in an Ames assay. An approach that led to the successful identification of nonmutagenic examples, as well as further optimization to compounds with reduced cardiovascular liabilities is described. Select pharmacokinetic and in vivo efficacy data are presented.
