Evobrutinib pathway to its major metabolite M463-2 and insights from a biotransformation and DDI perspective

Article Clinical Neurology

BTK inhibition limits B-cell-T-cell interaction through modulation of B-cell metabolism: implications for multiple sclerosis therapy

Rui Li et al.

Summary: Inhibition of Bruton's Tyrosine Kinase (BTKi) is a promising therapy for autoimmune diseases. This study demonstrates that BTKi attenuates B-cell:T-cell interactions by modulating B-cell metabolic pathways and mediates an anti-inflammatory modulation of B cells. The study suggests that targeting B-cell metabolism may be a viable therapeutic approach for pro-inflammatory B cells.

ACTA NEUROPATHOLOGICA (2022)

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Review Chemistry, Medicinal

Current Perspectives: Evidence to Date on BTK Inhibitors in the Management of Multiple Sclerosis

Edgar Carnero Contentti et al.

Summary: Multiple sclerosis is a chronic inflammatory disease of the central nervous system. B cells and myeloid cells play key roles in the development of the disease. BTK inhibitors show promise as novel therapeutic approaches for multiple sclerosis.

DRUG DESIGN DEVELOPMENT AND THERAPY (2022)

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Article Medicine, Research & Experimental

Evobrutinib, a covalent Bruton's tyrosine kinase inhibitor: Mass balance, elimination route, and metabolism in healthy participants

Holger Scheible et al.

Summary: The study found that evobrutinib is rapidly absorbed and metabolized, primarily excreted in feces and to a lesser extent in urine. Only one major metabolite, M463-2, was identified in plasma, supporting further development of evobrutinib and potentially guiding future investigations.

CTS-CLINICAL AND TRANSLATIONAL SCIENCE (2021)

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Review Biochemistry & Molecular Biology

Enantioselectivity in Drug Pharmacokinetics and Toxicity: Pharmacological Relevance and Analytical Methods

Maria Miguel Coelho et al.

Summary: Enzymes, receptors, and other binding molecules in biological processes can recognize enantiomers as different molecular entities, leading to diverse responses. Enantioselectivity is observed in drug pharmacodynamics and pharmacokinetics, influencing metabolic pathways and toxicity mechanisms. The configuration of enantiomers can cause unexpected effects during pharmacokinetic processes, with factors like genetic variability and drug interactions playing a role in the outcomes.

MOLECULES (2021)

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Review Clinical Neurology

B cells in multiple sclerosis - from targeted depletion to immune reconstitution therapies

Maria T. Cencioni et al.

Summary: This Review discusses the roles of B cells in multiple sclerosis, highlighting the involvement of B cells in disease pathogenesis and the potential mechanisms underlying the abnormalities in B cell function in MS.

NATURE REVIEWS NEUROLOGY (2021)

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Article Immunology