1242156-23-5

Basic information

• Product Name: RN486
• Synonyms: RN486;6-cyclopropyl-8-fluoro-2-(2-(hydroxyMethyl)-3-(1-Methyl-5-((5-(4-Methylpiperazin-1-yl)pyridin-2-yl)aMiNA)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)isoquiNAlin-1(2H)-one;6-cyclopropyl-8-fluoro-2-(2-(hydroxyMethyl)-3-(1-Methyl-5-(5-(4-Methylpiperazin-1-yl)pyridin-2-ylaMino)-6-oxo-1,6-dihydropyridin-3-yl)phenyl)isoquinolin-1(2H)-one;RN486/RN-486;RN468;6-Cyclopropyl-2-[3-[1,6-dihydro-1-methyl-5-[[5-(4-methyl-1-piperazinyl)-2-pyridinyl]amino]-6-oxo-3-pyridinyl]-2-(hydroxymethyl)phenyl]-8-fluoro-1(2H)-isoquinolinone;RN486 LM-2078;RN486 TFA Salt
• CAS NO: 1242156-23-5
• Molecular Formula: C₃₅H₃₅FN₆O₃
• Molecular Weight: 606.6892032
• EINECS: -0
• Product Categories: Inhibitors
• Mol File: 1242156-23-5.mol
• Article Data: 2

Chemical Properties

• Boiling Point: 868.6±65.0 °C(Predicted)
• Appearance: /
• Density: 1.378±0.06 g/cm3(Predicted)
• Solubility: ≥30.35 mg/mL in DMSO with gentle warming; insoluble in H2O; insoluble in EtOH
• PKA: 13.95±0.10(Predicted)
• CAS DataBase Reference: RN486(CAS DataBase Reference)
• NIST Chemistry Reference: RN486(1242156-23-5)
• EPA Substance Registry System: RN486(1242156-23-5)

Safety Data

• Hazardous Substances Data: 1242156-23-5(Hazardous Substances Data)

Usage

Description

RN486 is a potent inhibitor of Bruton's tyrosine kinase (Btk), a non-receptor tyrosine kinase that plays a crucial role in the regulation of immune cell signaling. It functions by blocking receptor cross-linking-induced degranulation in mast cells, which are involved in various immune responses. This inhibition can potentially be utilized in the treatment and prevention of autoimmune diseases and conditions where the immune system is overactive or misdirected.

Uses

Used in Pharmaceutical Industry:
RN486 is used as an immunomodulatory agent for the prevention and treatment of autoimmune diseases. By inhibiting Btk, it can help regulate the immune system and reduce the severity of conditions such as arthritis and other autoimmune disorders.
Used in Arthritis Treatment:
RN486 is used as an anti-inflammatory agent for the prevention and management of arthritis. Its ability to inhibit Btk and reduce mast cell degranulation can help alleviate the symptoms of arthritis, such as pain, swelling, and joint damage.
Used in Autoimmune Disease Management:
RN486 is used as a therapeutic agent for the treatment of various autoimmune diseases, where the immune system mistakenly attacks the body's own tissues. By targeting Btk, RN486 can help modulate the immune response and prevent the progression of these diseases.

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.

Upstream product

• 1242157-14-7 5-bromo-7-fluoro-2,3-dihydro-1H-inden-1-one 
• 1178884-45-1 5-bromo-1-methyl-3-((5-(4-methylpiperazin-1-yl)pyridin-2-yl)amino)pyridin-2(1H)-one 
• 395639-63-1 1-(4-bromo-2-fluorophenyl)-3-chloro-propan-1-one 
• 571189-49-6 5-(4-methyl-piperazin-1-yl)pyridin-2-ylamine 
• 657410-79-2 1-methyl-4-(6-nitro-pyridin-3-yl)-piperazine 
• 109-01-3 1-methyl-piperazine 
• 39856-50-3 5-bromo2-nitropyridine 
• 1242156-54-2 2-chloro-6-(6-cyclopropyl-8-fluoro-1-oxoisoquinolin-2 (1H)-yl)benzaldehyde 
• 151982-51-3 4-bromo-2-fluorobenzoyl chloride 
• 1242156-52-0 4-cyclopropyl-2-fluoro-6-methylbenzamide 
• 1242156-51-9 4-bromo-2-fluoro-6-methylbenzamide 
• 1242157-23-8 4-bromo-2-fluoro-6-methylbenzoic acid 
• 1242156-53-1 6-cyclopropyl-8-fluoro-1-oxoisoquinoline-2-(1H)-one 
• 1242157-16-9 6-cyclopropyl-8-fluoro-3,4-dihydroisoquinolin-1(2H)-one 

Relevant 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

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.