Remibrutinib

Remibrutinib (Rhapsido) belongs to small molecule inhibitors and is a highly selective, covalent Bruton's tyrosine kinase (BTK) inhibitor (IC50 = 1 nM) with oral activity and cell permeability. The IC50 for inhibiting BTK activity in blood is 0.23 μM. This compound can be used in research on chronic urticaria.

Btk enzymatic (B cell):0.023 μM, IL-8 (Cell-free assay):2.5 nM, CD69 (Cell-free assay):18 nM, BTK (Cell-free assay):1.3 nM, BTK:1 nM

Methods: Heparinized whole blood was collected and treated with Remibrutinib, then incubated with anti-IgE at 37°C and 5% CO₂ for 25 minutes. A basophil activation test was performed using flow cytometry to detect the proportion of CD63+ and CD203c+ basophils.
Results: Remibrutinib inhibited CD63 expression in a dose-dependent manner, with efficacy observed at a single 5 mg dose and near-complete inhibition achieved at ≥100 mg. The maximum inhibition rate of CD203c reached 84%, demonstrating potent in vitro inhibitory activity against basophil activation. [1]
Methods: Hirudin/citrate-anticoagulated human whole blood was collected and co-incubated with Remibrutinib at concentrations of 0.03–0.5 μM at 37°C for 1 hour. Platelet aggregation and in vitro bleeding time were assessed using multi-electrode aggregometry and the Platelet Function Analyzer-200.
Results: Remibrutinib inhibited GPVI-mediated platelet aggregation in a dose-dependent manner, with an IC₅₀ of 0.03 μM. At 0.1 μM, inhibition of the Btk-dependent pathway exceeded 90%, with significantly less impact on hemostatic function compared to rilzabrutinib. [2]

Methods:: Using experimental autoimmune encephalomyelitis mice expressing human/rat myelin oligodendrocyte glycoprotein as a model, Remibrutinib was suspended in 0.5% methylcellulose + 0.5% Tween 80 aqueous solution and administered by gavage from the day of immunization at doses of 3/30 mg/kg twice daily until the end of the experiment.
Results: Remibrutinib improved neurological symptoms in a dose-dependent manner, with 30 mg/kg significantly inhibiting disease progression without depleting B cells or reducing total immunoglobulin levels.[3]

DMSO: 240 mg/mL (472.88 mM), Sonication is recommended.

10% DMSO+40% PEG300+5% Tween 80+45% Saline: 5 mg/mL (9.85 mM), Sonication is recommended.