4.6 Review

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

Related references

Note: Only part of the references are listed.
Article Immunology

Co-Inhibition of the Immunoproteasome Subunits LMP2 and LMP7 Ameliorates Immune Thrombocytopenia

Sheng-hong Du et al.

Summary: The immunoproteasome, particularly the upregulation of LMP2, may play a role in the pathogenesis of immune thrombocytopenia (ITP). Specific inhibition of LMP2 had no significant impact on platelet count in ITP mice, while a dual LMP2 and LMP7 inhibitor increased platelet number. These findings suggest that immunoproteasome inhibition could be a potential therapeutic approach for ITP patients.

FRONTIERS IN IMMUNOLOGY (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)

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)

Review Biochemistry & Molecular Biology

Proteasome Inhibitors: Harnessing Proteostasis to Combat Disease

David J. Sherman et al.

MOLECULES (2020)

Article Chemistry, Medicinal

LMP2 Inhibitors as a Potential Treatment for Alzheimer's Disease

Deepak Bhattarai et al.

JOURNAL OF MEDICINAL CHEMISTRY (2020)

Article Chemistry, Medicinal

Covalent inhibitors: back on track?

Matthias Gehringer

FUTURE MEDICINAL CHEMISTRY (2020)

Article Chemistry, Medicinal

Structure-Activity Relationships of Noncovalent Immunoproteasome β5i-Selective Dipeptides

Wenhu Zhan et al.

JOURNAL OF MEDICINAL CHEMISTRY (2020)

Review Chemistry, Medicinal

Covalent Inhibition in Drug Discovery

Avick Kumar Ghosh et al.

CHEMMEDCHEM (2019)

Article Chemistry, Medicinal

Development of Novel Amides as Noncovalent Inhibitors of Immunoproteasomes

Roberta Ettari et al.

CHEMMEDCHEM (2019)

Review Pharmacology & Pharmacy

A Practical Review of Proteasome Pharmacology

Tiffany A. Thibaudeau et al.

PHARMACOLOGICAL REVIEWS (2019)

Article Biochemistry & Molecular Biology

Discovery of Immunoproteasome Inhibitors Using Large-Scale Covalent Virtual Screening

Andrea Scarpino et al.

MOLECULES (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

A focused structure-activity relationship study of psoralen-based immunoproteasome inhibitors

Eva Shannon Schiffrer et al.

MEDCHEMCOMM (2019)

Article Biochemistry & Molecular Biology

Non-covalent immunoproteasome inhibitors induce cell cycle arrest in multiple myeloma MM.1R cells

Roberta Ettari et al.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2019)

Article Biochemistry & Molecular Biology

Piperlongumine and some of its analogs inhibit selectively the human immunoproteasome over the constitutive proteasome

Elodie Bosc et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2018)

Article Medicine, Research & Experimental

The immunoproteasome-specific inhibitor ONX 0914 reverses susceptibility to acute viral myocarditis

Nadine Althof et al.

EMBO MOLECULAR MEDICINE (2018)

Review Medical Laboratory Technology

Next-generation proteasome inhibitors for cancer therapy

Ji Eun Park et al.

TRANSLATIONAL RESEARCH (2018)

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)

Review Chemistry, Medicinal

Covalent inhibitors design and discovery

Stephane De Cesco et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2017)

Review Biochemistry & Molecular Biology

Activity-based probes for the multicatalytic proteasome

David S. Hewings et al.

FEBS JOURNAL (2017)

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 Chemistry, Multidisciplinary

The Proteasome in Modern Drug Discovery: Second Life of a Highly Valuable Drug Target

Philipp M. Cromm et al.

ACS CENTRAL SCIENCE (2017)

Article Microbiology

LOW NEUROTOXICITY OF ONX-0914 SUPPORTS THE IDEA OF SPECIFIC IMMUNOPROTEASOME INHIBITION AS A SIDE-EFFECT-LIMITING, THERAPEUTIC STRATEGY

Laura von Brzezinski et al.

EUROPEAN JOURNAL OF MICROBIOLOGY AND IMMUNOLOGY (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

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 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 Multidisciplinary Sciences

A unified mechanism for proteolysis and autocatalytic activation in the 20S proteasome

Eva M. Huber et al.

NATURE COMMUNICATIONS (2016)

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)

Article Biochemistry & Molecular Biology

Crystal Structure of the Human 20S Proteasome in Complex with Carfilzomib

Wayne Harshbarger et al.

STRUCTURE (2015)

Article Pharmacology & Pharmacy

Anti-leukemic activity and mechanisms underlying resistance to the novel immunoproteasome inhibitor PR-924

Denise Niewerth et al.

BIOCHEMICAL PHARMACOLOGY (2014)

Review Biochemistry & Molecular Biology

Assembly of the 20S proteasome

Mary J. Kunjappu et al.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH (2014)

Article Chemistry, Medicinal

Selective immunoproteasome inhibitors with non-peptide scaffolds identified from structure-based virtual screening

Vinod Kasam et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2014)

Article Medicine, Research & Experimental

Inhibition of the immunoproteasome ameliorates experimental autoimmune encephalomyelitis

Michael Basler et al.

EMBO MOLECULAR MEDICINE (2014)

Article Biochemistry & Molecular Biology

Characterization of the Testis-specific Proteasome Subunit α4s in Mammals

Hiroyuki Uechi et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (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)

Review Biochemistry & Molecular Biology

The unique functions of tissue-specific proteasomes

Andrea Kniepert et al.

TRENDS IN BIOCHEMICAL SCIENCES (2014)

Article Chemistry, Medicinal

Oxathiazolones Selectively Inhibit the Human Immunoproteasome over the Constitutive Proteasome

Hao Fan et al.

ACS MEDICINAL CHEMISTRY LETTERS (2014)

Article Chemistry, Medicinal

Boronic Acid-Containing Proteasome Inhibitors: Alert to Potential Pharmaceutical Bioactivation

Austin C. Li et al.

CHEMICAL RESEARCH IN TOXICOLOGY (2013)

Article Oncology

U.S. Food and Drug Administration Approval: Carfilzomib for the Treatment of Multiple Myeloma

Thomas M. Herndon et al.

CLINICAL CANCER RESEARCH (2013)

Article Pharmacology & Pharmacy

Non-Covalent Proteasome Inhibitors

Julia Kaffy et al.

CURRENT PHARMACEUTICAL DESIGN (2013)

Article Multidisciplinary Sciences

Thymoproteasome subunit-β5T generates peptide-MHC complexes specialized for positive selection

Yan Xing et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2013)

Article Chemistry, Multidisciplinary

Cysteine protease inhibition by nitrile-based inhibitors: a computational study

Matthew G. Quesne et al.

FRONTIERS IN CHEMISTRY (2013)

Review Oncology

Efficacy of Bortezomib as First-Line Treatment for Patients with Multiple Myeloma

Utkarsh Painuly et al.

CLINICAL MEDICINE INSIGHTS-ONCOLOGY (2013)

Article Chemistry, Multidisciplinary

Hydroxyureas as Noncovalent Proteasome Inhibitors

Nerea Gallastegui et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2012)

Review Chemistry, Multidisciplinary

Inhibitors for the Immuno- and Constitutive Proteasome: Current and Future Trends in Drug Development

Eva Maria Huber et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2012)

Review Biochemistry & Molecular Biology

Covalent and non-covalent reversible proteasome inhibition

Philipp Beck et al.

BIOLOGICAL CHEMISTRY (2012)

Article Chemistry, Multidisciplinary

Exploiting nature's rich source of proteasome inhibitors as starting points in drug development

Melissa Ann Graewert et al.

CHEMICAL COMMUNICATIONS (2012)

Article Biochemistry & Molecular Biology

Reversible targeting of noncatalytic cysteines with chemically tuned electrophiles

Iana M. Serafimova et al.

NATURE CHEMICAL BIOLOGY (2012)

Review Cell Biology

Selective protein degradation in cell signalling

Han Liu et al.

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY (2012)

Review Biochemistry & Molecular Biology

Proteasome Activators

Beth M. Stadtmueller et al.

MOLECULAR CELL (2011)

Review Immunology

Towards a systems understanding of MHC class I and MHC class II antigen presentation

Jacques Neefjes et al.

NATURE REVIEWS IMMUNOLOGY (2011)

Article Immunology

Prevention of Experimental Colitis by a Selective Inhibitor of the Immunoproteasome

Michael Basler et al.

JOURNAL OF IMMUNOLOGY (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 Immunology

Proteasomes in immune cells: more than peptide producers?

Marcus Groettrup et al.

NATURE REVIEWS IMMUNOLOGY (2010)

Article Biochemistry & Molecular Biology

Intermediate-type 20 S proteasomes in HeLa cells: Asymmetric subunit composition, diversity and adaptation

Nicola Klare et al.

JOURNAL OF MOLECULAR BIOLOGY (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)

Article Pharmacology & Pharmacy

Human metabolism of the proteasome inhibitor bortezomib: Identification of circulating metabolites

T Pekol et al.

DRUG METABOLISM AND DISPOSITION (2005)

Review Cell Biology

Proteolysis and the Cell Cycle Introduction

Duncan J. Clarke

CELL CYCLE (2002)

Article Biochemistry & Molecular Biology

The structure of the mammalian 20S proteasome at 2.75 Å resolution

M Unno et al.

STRUCTURE (2002)

Article Biochemistry & Molecular Biology

A gated channel into the proteasome core particle

M Groll et al.

NATURE STRUCTURAL BIOLOGY (2000)