PRN 1008

Research use only, not for human use.

PRN1008 is a novel reversible, covalent and oral inhibitor of BTK with biochemical IC50 of 1.3 nM.

PRN1008 is a novel reversible, covalent and oral inhibitor of BTK with biochemical IC50 of 1.3 nM.(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.(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.

——

——

PRN1008

Tyrosine Kinase

BTK

BTK

——

——

1575596-29-0

665.774

C36H40FN9O3

>98% (HPLC)

DMSO : ≥ 130 mg/mL 195.27 mM

CC(C)(C=C(C#N)C(=O)N1CCCC(C1)N2C3=NC=NC(=C3C(=N2)C4=C(C=C(C=C4)OC5=CC=CC=C5)F)N)N6CCN(CC6)C7COC7

(R,E)-2-(3-(4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carbonyl)-4-methyl-4-(4-(oxetan-3-yl)piperazin-1-yl)pent-2-enenitrile

(-20℃)

With Ice Pack

≥ 2 years