Rilzabrutinib

Rilzabrutinib (PRN1008) is a reversible covalent, selective and oral active inhibitor of Bruton’s Tyrosine Kinase (BTK), with an IC₅₀ of 1.3 nM. IC50 & Target:1.3 nM (BTK)^[1][2]. In Vitro: Rilzabrutinib is a reversible covalent inhibitor of Bruton’s Tyrosine Kinase (BTK), with an IC₅₀ of 1.3±0.5 nM. Rilzabrutinib is also found to be highly selectively when tested in a panel of 251 other kinases. Cysteine targeting of BTK by Rilzabrutinib results in a slow off-rate demonstrated by retention of 79±2% of binding to BTK in PBMC 18 hours after washing away the compound in vitro. The covalent cysteine binding is completely reversible after denaturation of the target. Anti-IgM induces human B cell proliferation (10% serum) and B cell CD69 expression are inhibited by Rilzabrutinib with IC₅₀ of 5±2.4 nM and 123±38 nM, respectively^[2]. In Vivo: In vivo Rilzabrutinib demonstrates enduring pharmacodynamic effects after the compound has cleared from circulation, consistent with extended target residence time. Rilzabrutinib also reverses and completely suppresses collagen-induced arthritis in rats in a dose dependent manner which allows correlation of target occupancy and disease modification^[2].