Next-generation Bruton's tyrosine kinase inhibitor BIIB091 selectively and potently inhibits B cell and Fc receptor signaling and downstream functions in B cells and myeloid cells.

ABSTRACT:

Objectives

Bruton's tyrosine kinase (BTK) plays a non-redundant signaling role downstream of the B-cell receptor (BCR) in B cells and the receptors for the Fc region of immunoglobulins (FcR) in myeloid cells. Here, we characterise BIIB091, a novel, potent, selective and reversible small-molecule inhibitor of BTK.

Methods

BIIB091 was evaluated in vitro and in vivo in preclinical models and in phase 1 clinical trial.

Results

In vitro, BIIB091 potently inhibited BTK-dependent proximal signaling and distal functional responses in both B cells and myeloid cells with IC₅₀s ranging from 3 to 106 nm, including antigen presentation to T cells, a key mechanism of action thought to be underlying the efficacy of B cell-targeted therapeutics in mult

SUBMITTER: Bame E 

PROVIDER: S-EPMC8204096 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature