1242156-23-5 Usage
Biological activity
RN486 is an effective BTK inhibitor with an IC50 of 4 nM.
In vitro
RN486 not only potently and selectively inhibits the Btk enzyme, but also displays functional activities in human cell-based assays in multiple cell types, blocking Fcε receptor cross-linking-induced degranulation in mast cells (IC50 = 2.9 nM), Fcγ receptor engagement-mediated tumor necrosis factor α production in monocytes (IC50 = 7.0 nM), and B cell antigen receptor-induced expression of an activation marker, CD69, in B cells in whole blood (IC50 = 21.0 nM). RN486 is able to block the signaling of BCR as demonstrated by a marked inhibition of phosphorylation of both Btk and PLCγ2 in B cells. RN486 displays a selective B cell inhibitory profile in BioMAP Systems.
In vivo
RN486 displays similar functional activities in rodent models, effectively preventing type I and type III hypersensitivity responses. More importantly, RN486 produces robust anti-inflammatory and bone-protective effects in mouse CIA and rat adjuvant-induced arthritis (AIA) models. In the AIA model, RN486 inhibits both joint and systemic inflammation either alone or in combination with methotrexate, reducing both paw swelling and inflammatory markers in the blood.
Uses
RN 486 is a Bruton’s tyrosine kinase (Btk) inhibitor, blocking receptor cross-linking-induced degranulation in mast cells. May be used in the prevention of arthritis and other autoimmune diseases.
Check Digit Verification of cas no
The CAS Registry Mumber 1242156-23-5 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,2,4,2,1,5 and 6 respectively; the second part has 2 digits, 2 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 1242156-23:
(9*1)+(8*2)+(7*4)+(6*2)+(5*1)+(4*5)+(3*6)+(2*2)+(1*3)=115
115 % 10 = 5
So 1242156-23-5 is a valid CAS Registry Number.
1242156-23-5Relevant articles and documents
Structure-based drug design of RN486, a potent and selective Bruton's tyrosine kinase (BTK) inhibitor, for the treatment of rheumatoid arthritis
Lou, Yan,Han, Xiaochun,Kuglstatter, Andreas,Kondru, Rama K.,Sweeney, Zachary K.,Soth, Michael,McIntosh, Joel,Litman, Renee,Suh, Judy,Kocer, Buelent,Davis, Dana,Park, Jaehyeon,Frauchiger, Sandra,Dewdney, Nolan,Zecic, Hasim,Taygerly, Joshua P.,Sarma, Keshab,Hong, Junbae,Hill, Ronald J.,Gabriel, Tobias,Goldstein, David M.,Owens, Timothy D.
, p. 512 - 516 (2015/03/03)
Structure-based drug design was used to guide the optimization of a series of selective BTK inhibitors as potential treatments for Rheumatoid arthritis. Highlights include the introduction of a benzyl alcohol group and a fluorine substitution, each of which resulted in over 10-fold increase in activity. Concurrent optimization of drug-like properties led to compound 1 (RN486) (J. Pharmacol. Exp. Ther. 2012, 341, 90), which was selected for advanced preclinical characterization based on its favorable properties.
