4.7 Review

Site-Specific Proteasome Inhibitors

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Letter Neurosciences

Immunoproteasome Inhibitor ONX-0914 Affects Long-Term Potentiation in Murine Hippocampus

Alexander Maltsev et al.

JOURNAL OF NEUROIMMUNE PHARMACOLOGY (2021)

Review Biochemistry & Molecular Biology

Molecular and cellular dynamics of the 26S proteasome

Eri Sakata et al.

Summary: The ubiquitin-proteasome system in eukaryotic cells removes dysfunctional or unneeded proteins, with the 26S proteasome being a multisubunit complex consisting of a 20S core particle and one or two regulatory particles. Advances in single-particle cryo-electron microscopy have provided atomic resolution models of the proteasome, contributing to a better understanding of its dynamics. Cryo-electron tomography allows for structural studies in situ, offering molecular resolution images of macromolecules within preserved cellular environments.

BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS (2021)

Review Microbiology

Microbial proteasomes as drug targets

Hao Zhang et al.

Summary: Proteasomes are ATP-dependent, N-terminal nucleophile hydrolases that are essential for intracellular protein turnover and present in all biological kingdoms. Inhibiting proteasomes can be harmful to cell viability, but proteasome inhibitor drugs have revolutionized the treatment of multiple myeloma. Efforts are being made to develop inhibitors selective for microbial proteasomes, with promising progress in targeting pathogenic microbes for diseases like leishmaniasis and Chagas disease.

PLOS PATHOGENS (2021)

Article Chemistry, Medicinal

Macrocyclic Immunoproteasome Inhibitors as a Potential Therapy for Alzheimer's Disease

Min Jae Lee et al.

Summary: The development of iP-selective macrocyclic peptide epoxyketones, exemplified by DB-60, shows promising potential as an Alzheimer's disease drug candidate by effectively inhibiting iP activity, improving metabolic stability, and reducing inflammatory levels in mice, resulting in cognitive improvement.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Chemistry, Medicinal

Structure-Based Optimization and Discovery of M3258, a Specific Inhibitor of the Immunoproteasome Subunit LMP7 (β5i)

Markus Klein et al.

Summary: Proteasomes are essential components of the ubiquitin-dependent protein degradation pathway, with LMP7 being a subunit of the immunoproteasome. Current pan-proteasome inhibitors nonselectively target LMP7 and other subunits, limiting their therapeutic applicability. Novel amido boronic acids were discovered to selectively inhibit LMP7, leading to the identification of the highly potent and orally available inhibitor M3258, which showed strong antitumor activity in MM models.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Multidisciplinary Sciences

Activity of immunoproteasome inhibitor ONX-0914 in acute lymphoblastic leukemia expressing MLL-AF4 fusion protein

Tyler W. Jenkins et al.

Summary: Proteasome inhibitors bortezomib and carfilzomib have shown clinical efficacy for the treatment of acute lymphoblastic leukemia, but their toxicities may limit their use in pediatric patients. Targeting immunoproteasomes with ONX-0914 may provide a potential treatment option for ALL, especially in cases with the t(4;11)(q21;q23) chromosomal translocation.

SCIENTIFIC REPORTS (2021)

Review Cell Biology

A Nut for Every Bolt: Subunit-Selective Inhibitors of the Immunoproteasome and Their Therapeutic Potential

Eva M. Huber et al.

Summary: The review highlights the significance of immunoproteasome (iCP) inhibitors in scientific and medicinal applications, showcasing their potential in treating autoimmune diseases and chronic inflammations.
Review Biochemistry & Molecular Biology

The proteasome and its role in the nervous system

Fulya Turker et al.

Summary: Proteasomes are multisubunit complexes responsible for the degradation of most proteins in mammalian cells to maintain protein homeostasis and regulate cellular processes. They selectively remove unwanted proteins through a regulated gating mechanism, essential for preserving cellular function. Recent discoveries highlight the role of proteasomes in generating peptides with important cellular functions, challenging traditional beliefs about their primary function in protein elimination.

CELL CHEMICAL BIOLOGY (2021)

Review Pharmacology & Pharmacy

Proteasome Inhibitor Drugs

Lloyd D. Fricker

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 60 (2020)

Article Chemistry, Medicinal

The Immunoproteasome: An Emerging Target in Cancer and Autoimmune and Neurological Disorders

Breanna L. Zerfas et al.

JOURNAL OF MEDICINAL CHEMISTRY (2020)

Article Chemistry, Medicinal

LMP2 Inhibitors as a Potential Treatment for Alzheimer's Disease

Deepak Bhattarai et al.

JOURNAL OF MEDICINAL CHEMISTRY (2020)

Article Surgery

Plasma cell targeting to prevent antibody-mediated rejection

E. Steve Woodle et al.

AMERICAN JOURNAL OF TRANSPLANTATION (2020)

Article Chemistry, Medicinal

Structure-Activity Relationships of Noncovalent Immunoproteasome β5i-Selective Dipeptides

Wenhu Zhan et al.

JOURNAL OF MEDICINAL CHEMISTRY (2020)

Review Pharmacology & Pharmacy

A Practical Review of Proteasome Pharmacology

Tiffany A. Thibaudeau et al.

PHARMACOLOGICAL REVIEWS (2019)

Article Cell Biology

Non-lethal proteasome inhibition activates pro-tumorigenic pathways in multiple myeloma cells

Aikaterini Skorda et al.

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (2019)

Article Chemistry, Medicinal

Structure-Based Design of Inhibitors Selective for Human Proteasome β2c or β2i Subunits

Bo-Tao Xin et al.

JOURNAL OF MEDICINAL CHEMISTRY (2019)

Article Biochemistry & Molecular Biology

Proteasome Inhibition in Multiple Myeloma: Head-to-Head Comparison of Currently Available Proteasome Inhibitors

Andrej Besse et al.

CELL CHEMICAL BIOLOGY (2019)

Article Biochemistry & Molecular Biology

Co-inhibition of immunoproteasome subunits LMP2 and LMP7 is required to block autoimmunity

Michael Basler et al.

EMBO REPORTS (2018)

Article Pharmacology & Pharmacy

Amelioration of autoimmunity with an inhibitor selectively targeting all active centres of the immunoproteasome

Michael Basler et al.

BRITISH JOURNAL OF PHARMACOLOGY (2018)

Article Chemistry, Medicinal

Discovery of Highly Selective Inhibitors of the Immunoproteasome Low Molecular Mass Polypeptide 2 (LMP2) Subunit

Henry W. B. Johnson et al.

ACS MEDICINAL CHEMISTRY LETTERS (2017)

Article Multidisciplinary Sciences

Structure of human immunoproteasome with a reversible and noncompetitive inhibitor that selectively inhibits activated lymphocytes

Ruda de Luna Almeida Santos et al.

NATURE COMMUNICATIONS (2017)

Article Biochemistry & Molecular Biology

Structural Elucidation of a Nonpeptidic Inhibitor Specific for the Human Immunoproteasome

Haissi Cui et al.

CHEMBIOCHEM (2017)

Article Chemistry, Multidisciplinary

A Set of Activity-Based Probes to Visualize Human (Immuno)proteasome Activities

Gerjan de Bruin et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2016)

Article Chemistry, Multidisciplinary

Nonpeptidic Selective Inhibitors of the Chymotrypsin-Like (5i) Subunit of the Immunoproteasome

Izidor Sosic et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2016)

Article Chemistry, Medicinal

Immunoproteasome 5i-Selective Dipeptidomimetic Inhibitors

Pradeep K. Singh et al.

CHEMMEDCHEM (2016)

Article Biochemistry & Molecular Biology

A humanized yeast proteasome identifies unique binding modes of inhibitors for the immunosubunit 5i

Eva M. Huber et al.

EMBO JOURNAL (2016)

Article Chemistry, Medicinal

Structure-Based Design of β5c Selective Inhibitors of Human Constitutive Proteasomes

Bo-Tao Xin et al.

JOURNAL OF MEDICINAL CHEMISTRY (2016)

Article Multidisciplinary Sciences

Brief treatment with a highly selective immunoproteasome inhibitor promotes long-term cardiac allograft acceptance in mice

Esilida Sula Karreci et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2016)

Article Chemistry, Multidisciplinary

A Minimal -Lactone Fragment for Selective 5c or 5i Proteasome Inhibitors

Michael Groll et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2015)

Article Chemistry, Multidisciplinary

Identification of a β1/β2-Specific Sulfonamide Proteasome Ligand by Crystallographic Screening

Philipp Beck et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2015)

Article Chemistry, Multidisciplinary

Selective Inhibition of the Immunoproteasome by Structure-Based Targeting of a Non-catalytic Cysteine

Christian Dubiella et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2015)

Article Chemistry, Multidisciplinary

Systematic Analyses of Substrate Preferences of 20S Proteasomes Using Peptidic Epoxyketone Inhibitors

Eva M. Huber et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2015)

Review Biochemistry & Molecular Biology

Subunit specific inhibitors of proteasomes and their potential for immunomodulation

Alexei F. Kisselev et al.

CURRENT OPINION IN CHEMICAL BIOLOGY (2014)

Article Chemistry, Medicinal

Structure-Based Design of β1i or β5i Specific Inhibitors of Human Immunoproteasomes

Gerjan de Bruin et al.

JOURNAL OF MEDICINAL CHEMISTRY (2014)

Article Biochemistry & Molecular Biology

A FRET-based approach for identification of proteasome catalytic subunit composition

Ji Eun Park et al.

MOLECULAR BIOSYSTEMS (2014)

Article Chemistry, Medicinal

Oxathiazolones Selectively Inhibit the Human Immunoproteasome over the Constitutive Proteasome

Hao Fan et al.

ACS MEDICINAL CHEMISTRY LETTERS (2014)

Article Biochemistry & Molecular Biology

1,2,4-Oxadiazoles Identified by Virtual Screening and their Non-Covalent Inhibition of the Human 20S Proteasome

X. Marechal et al.

CURRENT MEDICINAL CHEMISTRY (2013)

Review Immunology

The immunoproteasome in antigen processing and other immunological functions

Michael Basler et al.

CURRENT OPINION IN IMMUNOLOGY (2013)

Article Biochemistry & Molecular Biology

A bright approach to the immunoproteasome: Development of LMP2/β1i-specific imaging probes

Kimberly Cornish Carmony et al.

BIOORGANIC & MEDICINAL CHEMISTRY (2012)

Review Biochemistry & Molecular Biology

Proteasome Inhibitors: An Expanding Army Attacking a Unique Target

Alexei F. Kisselev et al.

CHEMISTRY & BIOLOGY (2012)

Editorial Material Cell Biology

Development of proteasome inhibitors as research tools and cancer drugs

Alfred L. Goldberg

JOURNAL OF CELL BIOLOGY (2012)

Article Biochemistry & Molecular Biology

Molecular Model of the Human 26S Proteasome

Paula C. A. da Fonseca et al.

MOLECULAR CELL (2012)

Article Multidisciplinary Sciences

Complete subunit architecture of the proteasome regulatory particle

Gabriel C. Lander et al.

NATURE (2012)

Article Immunology

Mice completely lacking immunoproteasomes show major changes in antigen presentation

Eleanor Z. Kincaid et al.

NATURE IMMUNOLOGY (2012)

Article Oncology

New Proteasome Inhibitors in Myeloma

Panisinee Lawasut et al.

CURRENT HEMATOLOGIC MALIGNANCY REPORTS (2012)

Article Cell Biology

Proteostenosis and plasma cell pathophysiology

Simone Cenci et al.

CURRENT OPINION IN CELL BIOLOGY (2011)

Article Biochemistry & Molecular Biology

Nature of Pharmacophore Influences Active Site Specificity of Proteasome Inhibitors

Michael Screen et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2010)

Article Chemistry, Organic

A panel of subunit-selective activity-based proteasome probes

Martijn Verdoes et al.

ORGANIC & BIOMOLECULAR CHEMISTRY (2010)

Article Multidisciplinary Sciences

Two abundant proteasome subtypes that uniquely process some antigens presented by HLA class I molecules

Benoit Guillaume et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2010)

Article Multidisciplinary Sciences

Inhibitors selective for mycobacterial versus human proteasomes

Gang Lin et al.

NATURE (2009)

Article Immunology

Dampening Ab responses using proteasome inhibitors following in vivo B cell activation

Paolo Cascio et al.

EUROPEAN JOURNAL OF IMMUNOLOGY (2008)

Article Chemistry, Medicinal

A cell-permeable inhilbitor and activity-based probe for the caspase-like activity of the proteasome

Paul F. van Swieten et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2007)

Article Multidisciplinary Sciences

Regulation of CD8+ T cell development by thymus-specific proteasomes

Shigeo Murata et al.

SCIENCE (2007)

Article Biochemistry & Molecular Biology

LMP2-specific inhibitors: Chemical genetic tools for proteasome biology

Yik Khuan (Abby) Ho et al.

CHEMISTRY & BIOLOGY (2007)

Review Chemistry, Multidisciplinary

20S proteasome and its inhibitors: Crystallographic knowledge for drug development

Ljudmila Borissenko et al.

CHEMICAL REVIEWS (2007)

Article Immunology

An altered T cell repertoire in MECL-1-deficient mice

Michael Basler et al.

JOURNAL OF IMMUNOLOGY (2006)

Article Biochemistry & Molecular Biology

TMC-95-based inhibitor design provides evidence for the catalytic versatility of the proteasome

Michael Groll et al.

CHEMISTRY & BIOLOGY (2006)

Article Biochemistry & Molecular Biology

Importance of the different proteolytic sites of the proteasome and the efficacy of inhibitors varies with the protein substrate

AF Kisselev et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2006)

Article Biochemistry & Molecular Biology

Progressively impaired proteasomal capacity during terminal plasma cell differentiation

S Cenci et al.

EMBO JOURNAL (2006)

Article Chemistry, Medicinal

Peptidyl vinyl ester derivatives: New class of selective inhibitors of proteasome trypsin-like activity

M Marastoni et al.

JOURNAL OF MEDICINAL CHEMISTRY (2005)

Article Biochemical Research Methods

Activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib

CR Berkers et al.

NATURE METHODS (2005)

Review Biochemistry & Molecular Biology

Proteasome inhibitors: from research tools to drug candidates

AF Kisselev et al.

CHEMISTRY & BIOLOGY (2001)

Article Biochemistry & Molecular Biology

Lack of proteasome active site allostery as revealed by subunit-specific inhibitors

J Myung et al.

MOLECULAR CELL (2001)