Safety, pharmacokinetics and pharmacodynamics of branebrutinib (BMS‐986195), a covalent, irreversible inhibitor of Bruton's tyrosine kinase: Randomised phase I, placebo‐controlled trial in healthy participants

Branebrutinib (BMS‐986195) is a potent, highly selective, oral, small‐molecule, covalent inhibitor of Bruton's tyrosine kinase (BTK). This study evaluated safety, pharmacokinetics and pharmacodynamics of branebrutinib in healthy participants.

[1]  Robert J. Neely,et al.  Determination of Real Time in Vivo Drug Receptor Occupancy for a Covalent Binding Drug as a Clinical Pharmacodynamic Biomarker by Immunocapture-LC-MS/MS. , 2019, Analytical chemistry.

[2]  D. Arnold,et al.  Placebo-Controlled Trial of an Oral BTK Inhibitor in Multiple Sclerosis. , 2019, The New England journal of medicine.

[3]  M. Camps,et al.  Efficacy and Pharmacodynamic Modeling of the BTK Inhibitor Evobrutinib in Autoimmune Disease Models , 2019, The Journal of Immunology.

[4]  Michael A. Galella,et al.  Discovery of Branebrutinib (BMS-986195): A Strategy for Identifying a Highly Potent and Selective Covalent Inhibitor Providing Rapid in Vivo Inactivation of Bruton's Tyrosine Kinase (BTK). , 2019, Journal of medicinal chemistry.

[5]  Steve Alexander,et al.  Experimental design and analysis and their reporting II: updated and simplified guidance for authors and peer reviewers , 2018, British journal of pharmacology.

[6]  K. Hwang,et al.  HM71224, a selective Bruton’s tyrosine kinase inhibitor, attenuates the development of murine lupus , 2017, Arthritis Research & Therapy.

[7]  Marjolein J. W. de Bruijn,et al.  Enhanced Bruton's Tyrosine Kinase Activity in Peripheral Blood B Lymphocytes From Patients With Autoimmune Disease , 2017, Arthritis & rheumatology.

[8]  Lingyun Sun,et al.  Increased expression of Bruton’s tyrosine kinase in peripheral blood is associated with lupus nephritis , 2017, Clinical Rheumatology.

[9]  K. McIntyre,et al.  Small Molecule Reversible Inhibitors of Bruton's Tyrosine Kinase (BTK): Structure-Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide (BMS-935177). , 2016, Journal of medicinal chemistry.

[10]  PH van der Graaf,et al.  A Tutorial on Target-Mediated Drug Disposition (TMDD) Models , 2015, CPT: pharmacometrics & systems pharmacology.

[11]  Michael L. Wang,et al.  Selective antitumor activity of ibrutinib in EGFR-mutant non-small cell lung cancer cells. , 2014, Journal of the National Cancer Institute.

[12]  B. Chang,et al.  Bruton's tyrosine kinase inhibitors for the treatment of rheumatoid arthritis. , 2014, Drug discovery today.

[13]  J. Burger.  Bruton’s Tyrosine Kinase (BTK) Inhibitors in Clinical Trials , 2014, Current Hematologic Malignancy Reports.

[14]  L. Vargas,et al.  Inhibitors of BTK and ITK: State of the New Drugs for Cancer, Autoimmunity and Inflammatory Diseases , 2013, Scandinavian journal of immunology.

[15]  Juswinder Singh,et al.  Inhibition of Btk with CC-292 Provides Early Pharmacodynamic Assessment of Activity in Mice and Humans , 2013, The Journal of Pharmacology and Experimental Therapeutics.

[16]  R. Advani,et al.  Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  Georg Schett,et al.  The pathogenesis of rheumatoid arthritis. , 2011, The New England journal of medicine.

[18]  Brandon J. Bravo,et al.  Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis. , 2011, Nature chemical biology.

[19]  Mi‐Sun Kim,et al.  The Phosphoinositide 3-Kinase-Dependent Activation of Btk Is Required for Optimal Eicosanoid Production and Generation of Reactive Oxygen Species in Antigen-Stimulated Mast Cells1 , 2008, The Journal of Immunology.

[20]  M. Cybulsky,et al.  Dual Functions of Bruton’s Tyrosine Kinase and Tec Kinase during Fcγ Receptor-Induced Signaling and Phagocytosis1 , 2008, The Journal of Immunology.

[21]  Taesoo Kim,et al.  The Tec Family Tyrosine Kinase Btk Regulates RANKL-induced Osteoclast Maturation* , 2008, Journal of Biological Chemistry.

[22]  T. Kodama,et al.  Tyrosine Kinases Btk and Tec Regulate Osteoclast Differentiation by Linking RANK and ITAM Signals , 2008, Cell.

[23]  L. Honigberg,et al.  Discovery of Selective Irreversible Inhibitors for Bruton’s Tyrosine Kinase , 2007, ChemMedChem.

[24]  A. Halpern,et al.  HER1/EGFR inhibitor-associated rash: future directions for management and investigation outcomes from the HER1/EGFR inhibitor rash management forum. , 2005, The oncologist.

[25]  T. Ståhl,et al.  Expression of FcγRIII is required for development of collagen‐induced arthritis , 2002 .

[26]  J. Verbeek,et al.  Expression of FcgammaRIII is required for development of collagen-induced arthritis. , 2002, European journal of immunology.

[27]  A. Satterthwaite,et al.  The role of Bruton's tyrosine kinase in B-cell development and function: a genetic perspective. , 2000, Immunological reviews.

[28]  B. Heyman,et al.  Induction and Suppression of Collagen-Induced Arthritis Is Dependent on Distinct Fcγ Receptors , 2000, The Journal of experimental medicine.

[29]  H. Mano.  Tec family of protein-tyrosine kinases: an overview of their structure and function. , 1999, Cytokine & growth factor reviews.

[30]  F. Alt,et al.  Involvement of Bruton's Tyrosine Kinase in FcεRI-dependent Mast Cell Degranulation and Cytokine Production , 1998, The Journal of experimental medicine.

[31]  John D Lambris,et al.  Expression of Bruton's agammaglobulinemia tyrosine kinase gene, BTK, is selectively down-regulated in T lymphocytes and plasma cells. , 1994, Journal of immunology.