Molecular glues modulate protein functions by inducing protein aggregation: A promising therapeutic strategy of small molecules for disease treatment

The Rise of Molecular Glues

(2021) Stuart L. Schreiber   CELL

Robust Principal Component Analysis‐based Prediction of Protein‐Protein Interaction Hot spots ( RBHS )

(2021) Divya Sitani et al.   PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS

Targeting protein self-association in drug design

(2021) Léopold Thabault et al.   DRUG DISCOVERY TODAY

CC-90009: A Cereblon E3 Ligase Modulating Drug That Promotes Selective Degradation of GSPT1 for the Treatment of Acute Myeloid Leukemia

(2021) Joshua D. Hansen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Cullin-Ring Ligases as promising targets for gastric carcinoma treatment

(2021) Qianqian Song et al.   PHARMACOLOGICAL RESEARCH

Progress toward B-Cell Lymphoma 6 BTB Domain Inhibitors for the Treatment of Diffuse Large B-Cell Lymphoma and Beyond

(2021) Yong Ai et al.   JOURNAL OF MEDICINAL CHEMISTRY

The roles of PD-1/PD-L1 in the prognosis and immunotherapy of prostate cancer

(2021) Yichi Xu et al.   MOLECULAR THERAPY

FDA approves 100th monoclonal antibody product

(2021) Asher Mullard   NATURE REVIEWS DRUG DISCOVERY

GSK137, a potent small-molecule BCL6 inhibitor with in vivo activity, suppresses antibody responses in mice

(2021) Andrew C. Pearce et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

An Exploration of Chemical Properties Required for Cooperative Stabilization of the 14-3-3 Interaction with NF-κB—Utilizing a Reversible Covalent Tethering Approach

(2021) Madita Wolter et al.   JOURNAL OF MEDICINAL CHEMISTRY

Development of Alectinib-Based PROTACs as Novel Potent Degraders of Anaplastic Lymphoma Kinase (ALK)

(2021) Shaowen Xie et al.   JOURNAL OF MEDICINAL CHEMISTRY

Molecular Glues for Targeted Protein Degradation: From Serendipity to Rational Discovery

(2021) Guoqiang Dong et al.   JOURNAL OF MEDICINAL CHEMISTRY

Terphenyl-Based Small-Molecule Inhibitors of Programmed Cell Death-1/Programmed Death-Ligand 1 Protein–Protein Interaction

(2021) Damian Muszak et al.   JOURNAL OF MEDICINAL CHEMISTRY

Novel Biphenyl Pyridines as Potent Small-Molecule Inhibitors Targeting the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Interaction

(2021) Tianyu Wang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Syntheses, Biological Evaluations, and Mechanistic Studies of Benzo[c][1,2,5]oxadiazole Derivatives as Potent PD-L1 Inhibitors with In Vivo Antitumor Activity

(2021) Liu Liu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Identification of Potent, Selective, and Orally Bioavailable Small-Molecule GSPT1/2 Degraders from a Focused Library of Cereblon Modulators

(2021) Gisele Nishiguchi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Design, Synthesis, and Evaluation of o-(Biphenyl-3-ylmethoxy)nitrophenyl Derivatives as PD-1/PD-L1 Inhibitors with Potent Anticancer Efficacy In Vivo

(2021) Yiqiang OuYang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Recent Progress and Clinical Development of Inhibitors that Block MDM4/p53 Protein–Protein Interactions

(2021) Shiyan Zhang et al.   JOURNAL OF MEDICINAL CHEMISTRY

TF-PROTACs Enable Targeted Degradation of Transcription Factors

(2021) Jing Liu et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Reversible Covalent Imine-Tethering for Selective Stabilization of 14-3-3 Hub Protein Interactions

(2021) Peter J. Cossar et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Immune checkpoint inhibitors in melanoma

(2021) Matteo S Carlino et al.   LANCET

Design, Synthesis, and Pharmacological Evaluation of Biaryl-Containing PD-1/PD-L1 Interaction Inhibitors Bearing a Unique Difluoromethyleneoxy Linkage

(2021) Zilan Song et al.   JOURNAL OF MEDICINAL CHEMISTRY

Trivalent PROTACs enhance protein degradation via combined avidity and cooperativity

(2021) Satomi Imaide et al.   Nature Chemical Biology

Mapping, Structure and Modulation of PPI

(2021) Elisa Martino et al.   Frontiers in Chemistry

Functional Disruption of the Cancer-Relevant Interaction between Survivin and Histone H3 with a Guanidiniocarbonyl Pyrrole Ligand

(2020) Cecilia Vallet et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Targeting selective autophagy by AUTAC degraders

(2020) Daiki Takahashi et al.   Autophagy

Structure-based stabilization of non-native protein-protein interactions of coronavirus nucleocapsid proteins in antiviral drug design

(2020) Shan-Meng Lin et al.   JOURNAL OF MEDICINAL CHEMISTRY

A pneumonia outbreak associated with a new coronavirus of probable bat origin

(2020) Peng Zhou et al.   NATURE

A Novel Coronavirus from Patients with Pneumonia in China, 2019

(2020) Na Zhu et al.   NEW ENGLAND JOURNAL OF MEDICINE

Facts, Patterns and Principles in Drug Discovery: appraising the Rule of 5 with measured physicochemical data.

(2020) Christopher P. Tinworth et al.   JOURNAL OF MEDICINAL CHEMISTRY

Achieving In Vivo Target Depletion through the Discovery and Optimization of Benzimidazolone BCL6 Degraders

(2020) Benjamin R. Bellenie et al.   JOURNAL OF MEDICINAL CHEMISTRY

Unifying principles of bifunctional, proximity-inducing small molecules

(2020) Christopher J. Gerry et al.   Nature Chemical Biology

A Structural View of SARS-CoV-2 RNA Replication Machinery: RNA Synthesis, Proofreading and Final Capping

(2020) Maria Romano et al.   Cells

Design and synthesis of peptide-based chimeric molecules to induce degradation of the estrogen and androgen receptors

(2020) Hidetomo Yokoo et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Lysosome-targeting chimaeras for degradation of extracellular proteins

(2020) Steven M. Banik et al.   NATURE

New class of molecule targets proteins outside cells for degradation

(2020) Claire Whitworth et al.   NATURE

The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K

(2020) Mikołaj Słabicki et al.   NATURE

Structural insights into probe-dependent positive allosterism of the GLP-1 receptor

(2020) Ana B. Bueno et al.   Nature Chemical Biology

Rational discovery of molecular glue degraders via scalable chemical profiling

(2020) Cristina Mayor-Ruiz et al.   Nature Chemical Biology

Structure based design of bicyclic peptide inhibitors of RbAp48

(2020) Herbert Waldmann et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Discovery of a molecular glue promoting CDK12-DDB1 interaction to trigger cyclin K degradation

(2020) Lu Lv et al.   eLife

Fluorescence Anisotropy-Based Tethering for Discovery of Protein–Protein Interaction Stabilizers

(2020) Eline Sijbesma et al.   ACS Chemical Biology

Cereblon Modulators Target ZBTB16 and Its Oncogenic Fusion Partners for Degradation via Distinct Structural Degrons

(2020) Mary E Matyskiela et al.   ACS Chemical Biology

Small-molecule-induced polymerization triggers degradation of BCL6

(2020) Mikołaj Słabicki et al.   NATURE

NEDD8 and ubiquitin ligation by cullin-RING E3 ligases

(2020) Kheewoong Baek et al.   CURRENT OPINION IN STRUCTURAL BIOLOGY

A novel cereblon modulator for targeted protein degradation

(2019) Sung Ah Kim et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Prospective discovery of small molecule enhancers of an E3 ligase-substrate interaction

(2019) Kyle R. Simonetta et al.   Nature Communications

Site-Directed Fragment-Based Screening for the Discovery of Protein–Protein Interaction Stabilizers

(2019) Eline Sijbesma et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Germinal center‐derived lymphomas: The darkest side of humoral immunity

(2019) Coraline Mlynarczyk et al.   IMMUNOLOGICAL REVIEWS

Patterns of substrate affinity, competition and degradation kinetics underlie biological activity of thalidomide analogs

(2019) Adam S. Sperling et al.   BLOOD

Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Infection, Immunological Response, and Vaccine Development

(2019) Ayman Mubarak et al.   Journal of Immunology Research

A Small Molecule Targeting Mutagenic Translesion Synthesis Improves Chemotherapy

(2019) Jessica L. Wojtaszek et al.   CELL

REV1-POL ζ Inhibition and Cancer Therapy

(2019) Toshiyasu Taniguchi   MOLECULAR CELL

Lysosomes as a therapeutic target

(2019) Srinivasa Reddy Bonam et al.   NATURE REVIEWS DRUG DISCOVERY

Progress in PD-1/PD-L1 pathway inhibitors: From biomacromolecules to small molecules

(2019) Xin Lin et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Allele-selective lowering of mutant HTT protein by HTT–LC3 linker compounds

(2019) Zhaoyang Li et al.   NATURE

p63 is a cereblon substrate involved in thalidomide teratogenicity

(2019) Tomoko Asatsuma-Okumura et al.   Nature Chemical Biology

Structural complementarity facilitates E7820-mediated degradation of RBM39 by DCAF15

(2019) Tyler B. Faust et al.   Nature Chemical Biology

Structural Basis and Kinetic Pathway of RBM39 Recruitment to DCAF15 by a Sulfonamide Molecular Glue E7820

(2019) Xinlin Du et al.   STRUCTURE

Structure-Based Design of a Macrocyclic PROTAC

(2019) Andrea Testa et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

AUTACs: Cargo-Specific Degraders Using Selective Autophagy

(2019) Daiki Takahashi et al.   MOLECULAR CELL

Structures of MERS-CoV spike glycoprotein in complex with sialoside attachment receptors

(2019) Young-Jun Park et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

The Human Transcription Factors

(2018) Samuel A. Lambert et al.   CELL

BCL6 as a therapeutic target for lymphoma

(2018) Rebecca J Leeman-Neill et al.   EXPERT OPINION ON THERAPEUTIC TARGETS

Bicyclic Helical Peptides as Dual Inhibitors Selective for Bcl2A1 and Mcl-1 Proteins

(2018) Aline D. de Araujo et al.   JOURNAL OF MEDICINAL CHEMISTRY

Dual inhibition of MDMX and MDM2 as a therapeutic strategy in leukemia

(2018) Luis A. Carvajal et al.   Science Translational Medicine

mHTT Seeding Activity: A Marker of Disease Progression and Neurotoxicity in Models of Huntington’s Disease

(2018) Anne Ast et al.   MOLECULAR CELL

Dynamic Imaging of Small Molecule Induced Protein–Protein Interactions in Living Cells with a Fluorophore Phase Transition Based Approach

(2018) Chan-I Chung et al.   ANALYTICAL CHEMISTRY

Stabilized helical peptides: overview of the technologies and its impact on drug discovery

(2017) Mark Klein   Expert Opinion on Drug Discovery

Discovery of Pyrazolo[1,5-a]pyrimidine B-Cell Lymphoma 6 (BCL6) Binders and Optimization to High Affinity Macrocyclic Inhibitors

(2017) William McCoull et al.   JOURNAL OF MEDICINAL CHEMISTRY

Protac-Induced Protein Degradation in Drug Discovery: Breaking the Rules or Just Making New Ones?

(2017) Ian Churcher   JOURNAL OF MEDICINAL CHEMISTRY

Global profiling of lysine reactivity and ligandability in the human proteome

(2017) Stephan M. Hacker et al.   Nature Chemistry

Targeted protein degradation by PROTACs

(2017) Taavi K. Neklesa et al.   PHARMACOLOGY & THERAPEUTICS

Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15

(2017) Ting Han et al.   SCIENCE

pSILAC mass spectrometry reveals ZFP91 as IMiD-dependent substrate of the CRL4CRBN ubiquitin ligase

(2017) Jian An et al.   Nature Communications

Chemically Induced Degradation of the Oncogenic Transcription Factor BCL6

(2017) Nina Kerres et al.   Cell Reports

A novel cereblon modulator recruits GSPT1 to the CRL4CRBN ubiquitin ligase

(2016) Mary E. Matyskiela et al.   NATURE

Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors

(2016) Tinghu Zhang et al.   Nature Chemical Biology

Induced protein degradation: an emerging drug discovery paradigm

(2016) Ashton C. Lai et al.   NATURE REVIEWS DRUG DISCOVERY

Structural basis for small molecule targeting of the programmed death ligand 1 (PD-L1)

(2016) Krzysztof M. Zak et al.   Oncotarget

Peptide therapeutics: Targeting the undruggable space

(2015) Natia Tsomaia   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Programmed death-1 checkpoint blockade in acute myeloid leukemia

(2015) Alison Sehgal et al.   EXPERT OPINION ON BIOLOGICAL THERAPY

Lenalidomide induces ubiquitination and degradation of CK1α in del(5q) MDS

(2015) Jan Krönke et al.   NATURE

Combination cancer immunotherapy and new immunomodulatory targets

(2015) Kathleen M. Mahoney et al.   NATURE REVIEWS DRUG DISCOVERY

Structural Basis for the Identification of the N-Terminal Domain of Coronavirus Nucleocapsid Protein as an Antiviral Target

(2014) Shing-Yen Lin et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure of the DDB1–CRBN E3 ubiquitin ligase in complex with thalidomide

(2014) Eric S. Fischer et al.   NATURE

Neuronal targets for reducing mutant huntingtin expression to ameliorate disease in a mouse model of Huntington's disease

(2014) Nan Wang et al.   NATURE MEDICINE

Screening Bicyclic Peptide Libraries for Protein–Protein Interaction Inhibitors: Discovery of a Tumor Necrosis Factor-α Antagonist

(2013) Wenlong Lian et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells

(2013) J. Kronke et al.   SCIENCE

The Vital Role of Polymerase ζ and REV1 in Mutagenic, but Not Correct, DNA Synthesis across Benzo[a]pyrene-dG and Recruitment of Polymerase ζ by REV1 to Replication-stalled Site

(2012) Keiji Hashimoto et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Activation of the p53 pathway by small-molecule-induced MDM2 and MDMX dimerization

(2012) B. Graves et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Chaperone-mediated autophagy: a unique way to enter the lysosome world

(2012) Susmita Kaushik et al.   TRENDS IN CELL BIOLOGY

Drugs for Allosteric Sites on Receptors

(2011) Cody J. Wenthur et al.   Annual Review of Pharmacology and Toxicology

Potent and Selective Antisense Oligonucleotides Targeting Single-Nucleotide Polymorphisms in the Huntington Disease Gene / Allele-Specific Silencing of Mutant Huntingtin

(2011) Jeffrey B Carroll et al.   MOLECULAR THERAPY

Identification of a Primary Target of Thalidomide Teratogenicity

(2010) T. Ito et al.   SCIENCE

The p53 orchestra: Mdm2 and Mdmx set the tone

(2010) Mark Wade et al.   TRENDS IN CELL BIOLOGY