2 research outputs found
Discovery of GDC-0853: A Potent, Selective, and Noncovalent Bruton’s Tyrosine Kinase Inhibitor in Early Clinical Development
Bruton’s
tyrosine kinase (Btk) is a nonreceptor cytoplasmic
tyrosine kinase involved in B-cell and myeloid cell activation, downstream
of B-cell and Fcγ receptors, respectively. Preclinical studies
have indicated that inhibition of Btk activity might offer a potential
therapy in autoimmune diseases such as rheumatoid arthritis and systemic
lupus erythematosus. Here we disclose the discovery and preclinical
characterization of a potent, selective, and noncovalent Btk inhibitor
currently in clinical development. GDC-0853 (<b>29</b>) suppresses
B cell- and myeloid cell-mediated components of disease and demonstrates
dose-dependent activity in an <i>in vivo</i> rat model of
inflammatory arthritis. It demonstrates highly favorable safety, pharmacokinetic
(PK), and pharmacodynamic (PD) profiles in preclinical and Phase 2
studies ongoing in patients with rheumatoid arthritis, lupus, and
chronic spontaneous urticaria. On the basis of its potency, selectivity,
long target residence time, and noncovalent mode of inhibition, <b>29</b> has the potential to be a best-in-class Btk inhibitor for
a wide range of immunological indications
Discovery of GDC-0853: A Potent, Selective, and Noncovalent Bruton’s Tyrosine Kinase Inhibitor in Early Clinical Development
Bruton’s
tyrosine kinase (Btk) is a nonreceptor cytoplasmic
tyrosine kinase involved in B-cell and myeloid cell activation, downstream
of B-cell and Fcγ receptors, respectively. Preclinical studies
have indicated that inhibition of Btk activity might offer a potential
therapy in autoimmune diseases such as rheumatoid arthritis and systemic
lupus erythematosus. Here we disclose the discovery and preclinical
characterization of a potent, selective, and noncovalent Btk inhibitor
currently in clinical development. GDC-0853 (<b>29</b>) suppresses
B cell- and myeloid cell-mediated components of disease and demonstrates
dose-dependent activity in an <i>in vivo</i> rat model of
inflammatory arthritis. It demonstrates highly favorable safety, pharmacokinetic
(PK), and pharmacodynamic (PD) profiles in preclinical and Phase 2
studies ongoing in patients with rheumatoid arthritis, lupus, and
chronic spontaneous urticaria. On the basis of its potency, selectivity,
long target residence time, and noncovalent mode of inhibition, <b>29</b> has the potential to be a best-in-class Btk inhibitor for
a wide range of immunological indications