PRN1008

1575596-29-0

C36H40FN9O3

DMSO : >= 130 mg/mL (195.27 mM)

Protein Tyrosine Kinase/RTK

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: PRN1008 is a reversible covalent inhibitor of Bruton�s Tyrosine Kinase (BTK), with an IC₅₀ of 1.3+/-0.5 nM. PRN1008 is also found to be highly selectively when tested in a panel of 251 other kinases. Cysteine targeting of BTK by PRN1008 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 PRN1008 with IC₅₀ of 5+/-2.4 nM and 123+/-38 nM, respectively^[2]. In Vivo: In vivo PRN1008 demonstrates enduring pharmacodynamic effects after the compound has cleared from circulation, consistent with extended target residence time. PRN1008 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].