Rilzabrutinib_product_DataBase

Bioactivity

Rilzabrutinib (PRN1008) is a reversible covalent, selective and oral active inhibitor of Bruton’s Tyrosine Kinase (BTK), with an IC50 of 1.3 nM.

Invitro

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].

Name

Rilzabrutinib

CAS

1575596-29-0

Formula

C36H40FN9O3

Molar Mass

665.76

Appearance

Solid

Transport

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Reference

[1]. Smith PF, et al. A phase I trial of PRN1008, a novel reversible covalent inhibitor of Bruton's tyrosine kinase, in healthy volunteers. Br J Clin Pharmacol. 2017 Nov;83(11):2367-2376. [2]. Hill RJ, Bradshaw JM, Bisconte A, Tam D, Owens TD, Brameld KA, Smith PF, Funk JO, Goldstein DM, Nunn PA. Preclinical Characterization of PRN1008, a Novel Reversible Covalent Inhibitor of BTK that Shows Efficacy in a RAT Model of Collagen-Induced Arthritis

PeptideDB

Rilzabrutinib

CAS: 1575596-29-0 F: C36H40FN9O3 W: 665.76