Small-molecule PROTACs: novel agents for cancer therapy

Discovery of potent epidermal growth factor receptor (EGFR) degraders by proteolysis targeting chimera (PROTAC)

(2020) Hao Zhang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Developing potent PROTACs tools for selective degradation of HDAC6 protein

(2019) Zixuan An et al.   Protein & Cell

Degradation of Bruton’s tyrosine kinase mutants by PROTACs for potential treatment of ibrutinib-resistant non-Hodgkin lymphomas

(2019) Yonghui Sun et al.   LEUKEMIA

Recent development of CDK inhibitors: An overview of CDK/inhibitor co-crystal structures

(2019) Weiyan Cheng et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Selective Degradation of CDK6 by a Palbociclib Based PROTAC

(2019) Sandeep Rana et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Development of Dual and Selective Degraders of Cyclin-Dependent Kinases 4 and 6

(2019) Baishan Jiang et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

From Inhibition to Degradation: Targeting the Anti-apoptotic Protein Myeloid Cell Leukemia 1 (MCL1)

(2019) James William Papatzimas et al.   JOURNAL OF MEDICINAL CHEMISTRY

Acquired Resistance to BET-PROTACs(Proteolysis Targeting Chimeras) Caused by Genomic Alterations in Core Components of E3 ligase Complexes

(2019) Lu Zhang et al.   MOLECULAR CANCER THERAPEUTICS

FAIRLANE, a double-blind placebo-controlled randomized phase II trial of neoadjuvant ipatasertib plus paclitaxel for early triple-negative breast cancer

(2019) M Oliveira et al.   ANNALS OF ONCOLOGY

Small molecule PROTACs in targeted therapy: An emerging strategy to induce protein degradation

(2019) Meiyang Xi et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Potent and Preferential Degradation of CDK6 via Proteolysis Targeting Chimera Degraders

(2019) Shang Su et al.   JOURNAL OF MEDICINAL CHEMISTRY

Proteolysis Targeting Chimeras for the Selective Degradation of Mcl-1/Bcl-2 Derived from Nonselective Target Binding Ligands

(2019) Ziqian Wang et al.   JOURNAL OF MEDICINAL CHEMISTRY

PROTACs as Potential Therapeutic Agents for Cancer Drug Resistance

(2019) Xiuyun Sun et al.   BIOCHEMISTRY

Hot-Spots of Mcl-1 Protein

(2019) Camille Denis et al.   JOURNAL OF MEDICINAL CHEMISTRY

Targeted protein degradation: expanding the toolbox

(2019) Matthieu Schapira et al.   NATURE REVIEWS DRUG DISCOVERY

Development of selective mono or dual PROTAC degrader probe of CDK isoforms

(2019) Fei Zhou et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity

(2019) Sajid Khan et al.   NATURE MEDICINE

Translation Termination Factor GSPT1 Is a Phenotypically Relevant Off-Target of Heterobifunctional Phthalimide Degraders

(2018) Mette Ishoey et al.   ACS Chemical Biology

Targeting the C481S Ibrutinib-Resistance Mutation in Bruton’s Tyrosine Kinase Using PROTAC-Mediated Degradation

(2018) Alexandru D. Buhimschi et al.   BIOCHEMISTRY

Novel leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry

(2018) Jiangying Cao et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Development of the first small molecule histone deacetylase 6 (HDAC6) degraders

(2018) Ka Yang et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

PROTAC-induced BTK degradation as a novel therapy for mutated BTK C481S induced ibrutinib-resistant B-cell malignancies

(2018) Yonghui Sun et al.   CELL RESEARCH

Preclinical and clinical development of palbociclib and future perspectives

(2018) E. Martínez de Dueñas et al.   Clinical & Translational Oncology

Proteolysis Targeting Chimeras (PROTACs) of Anaplastic Lymphoma Kinase (ALK)

(2018) Chengwei Zhang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Phthalimide conjugations for the degradation of oncogenic PI3K

(2018) Wenlu Li et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Small-molecule Mcl-1 inhibitors: Emerging anti-tumor agents

(2018) Yichao Wan et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Molecular targeted therapy: treating cancer with specificity

(2018) Yeuan Ting Lee et al.   EUROPEAN JOURNAL OF PHARMACOLOGY

Chemically Induced Degradation of Anaplastic Lymphoma Kinase (ALK)

(2018) Chelsea E. Powell et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable Tumor Regression

(2018) Chong Qin et al.   JOURNAL OF MEDICINAL CHEMISTRY

Delineating the role of cooperativity in the design of potent PROTACs for BTK

(2018) Adelajda Zorba et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Induced protein degradation of anaplastic lymphoma kinase (ALK) by proteolysis targeting chimera (PROTAC)

(2018) Chung Hyo Kang et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

Discovery of Wogonin-based PROTACs against CDK9 and capable of achieving antitumor activity

(2018) Jinlei Bian et al.   BIOORGANIC CHEMISTRY

Chemically induced degradation of CK2 by proteolysis targeting chimeras based on a ubiquitin–proteasome pathway

(2018) Hong Chen et al.   BIOORGANIC CHEMISTRY

Pharmacological difference between degrader and inhibitor against oncogenic BCR-ABL kinase

(2018) Norihito Shibata et al.   Scientific Reports

Sorafenib: key lessons from over 10 years of experience

(2018) Bernard Escudier et al.   Expert Review of Anticancer Therapy

Iterative Design and Optimization of Initially Inactive Proteolysis Targeting Chimeras (PROTACs) Identify VZ185 as a Potent, Fast, and Selective von Hippel–Lindau (VHL) Based Dual Degrader Probe of BRD9 and BRD7

(2018) Vittoria Zoppi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Enhancing Antiproliferative Activity and Selectivity of a FLT-3 Inhibitor by Proteolysis Targeting Chimera Conversion

(2018) George M. Burslem et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Discovery of a series of dihydroquinoxalin-2(1 H )-ones as selective BET inhibitors from a dual PLK1-BRD4 inhibitor

(2017) Jianping Hu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Alkoxyurea-Based Histone Deacetylase Inhibitors Increase Cisplatin Potency in Chemoresistant Cancer Cell Lines

(2017) Katharina Stenzel 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

Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression

(2017) Bing Zhou et al.   JOURNAL OF MEDICINAL CHEMISTRY

Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation

(2017) Calla M Olson et al.   Nature Chemical Biology

Alectinib versus Crizotinib in Untreated ALK-Positive Non–Small-Cell Lung Cancer

(2017) Solange Peters et al.   NEW ENGLAND JOURNAL OF MEDICINE

Inhibitors of cyclin-dependent kinases as cancer therapeutics

(2017) Steven R. Whittaker et al.   PHARMACOLOGY & THERAPEUTICS

CDK4/6 Inhibition as a therapeutic strategy in breast cancer: palbociclib, ribociclib, and abemaciclib

(2017) Bahar Laderian et al.   SEMINARS IN ONCOLOGY

Homo-PROTACs: bivalent small-molecule dimerizers of the VHL E3 ubiquitin ligase to induce self-degradation

(2017) Chiara Maniaci et al.   Nature Communications

Targeting ALK: Precision Medicine Takes on Drug Resistance

(2017) Jessica J. Lin et al.   Cancer Discovery

Small-Molecule PROTACS: New Approaches to Protein Degradation

(2016) Momar Toure et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

A phase 1 clinical trial of flavopiridol consolidation in chronic lymphocytic leukemia patients following chemoimmunotherapy

(2016) Farrukh T. Awan et al.   ANNALS OF HEMATOLOGY

Development of BCR-ABL degradation inducers via the conjugation of an imatinib derivative and a cIAP1 ligand

(2016) Yosuke Demizu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

The BET-Bromodomain Inhibitor JQ1 Reduces Inflammation and Tau Phosphorylation at Ser396 in the Brain of the 3xTg Model of Alzheimer's Disease

(2016) Marco Magistri et al.   Current Alzheimer Research

Recent progress of cyclin-dependent kinase inhibitors as potential anticancer agents

(2016) Tinghan Li et al.   Future Medicinal Chemistry

Expanding the Cancer Arsenal with Targeted Therapies: Disarmament of the Antiapoptotic Bcl-2 Proteins by Small Molecules

(2016) Jeremy L. Yap et al.   JOURNAL OF MEDICINAL CHEMISTRY

On-Demand Targeting: Investigating Biology with Proximity-Directed Chemistry

(2016) Marcus J. C. Long et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models

(2016) András Kotschy et al.   NATURE

Structural basis of lenalidomide-induced CK1α degradation by the CRL4CRBN ubiquitin ligase

(2016) Georg Petzold et al.   NATURE

Inhibition of Mcl-1 through covalent modification of a noncatalytic lysine side chain

(2016) Gizem Akçay et al.   Nature Chemical Biology

Induced protein degradation: an emerging drug discovery paradigm

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

PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer

(2016) Kanak Raina et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Potent and selective chemical probe of hypoxic signalling downstream of HIF-α hydroxylation via VHL inhibition

(2016) Julianty Frost et al.   Nature Communications

Protein Degradation by In-Cell Self-Assembly of Proteolysis Targeting Chimeras

(2016) Honorine Lebraud et al.   ACS Central Science

Selective Small Molecule Induced Degradation of the BET Bromodomain Protein BRD4

(2015) Michael Zengerle et al.   ACS Chemical Biology

Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL

(2015) Ashton C. Lai et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Widening Synthesis Bottlenecks: Realization of Ultrafast and Continuous-Flow Synthesis of High-Silica Zeolite SSZ-13 for NOxRemoval

(2015) Zhendong Liu et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Cereblon binding molecules in multiple myeloma

(2015) K.M. Kortüm et al.   BLOOD REVIEWS

Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4

(2015) Jing Lu et al.   CHEMISTRY & BIOLOGY

Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia

(2015) J. F. Zeidner et al.   HAEMATOLOGICA

Structure-Guided Design of a Series of MCL-1 Inhibitors with High Affinity and Selectivity

(2015) Milan Bruncko et al.   JOURNAL OF MEDICINAL CHEMISTRY

Catalytic in vivo protein knockdown by small-molecule PROTACs

(2015) Daniel P Bondeson et al.   Nature Chemical Biology

The history and future of targeting cyclin-dependent kinases in cancer therapy

(2015) Uzma Asghar et al.   NATURE REVIEWS DRUG DISCOVERY

Phthalimide conjugation as a strategy for in vivo target protein degradation

(2015) G. E. Winter et al.   SCIENCE

BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia cells

(2015) Marie-Magdelaine Coudé et al.   Oncotarget

Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia

(2015) J. F. Zeidner et al.   HAEMATOLOGICA

Small-Molecule Control of Intracellular Protein Levels through Modulation of the Ubiquitin Proteasome System

(2014) Dennis L. Buckley et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Mechanism-based pharmacokinetic/pharmacodynamic meta-analysis of navitoclax (ABT-263) induced thrombocytopenia

(2014) Aksana Kaefer et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Small-Molecule Inhibitors of Protein-Protein Interactions: Progressing toward the Reality

(2014) Michelle R. Arkin et al.   CHEMISTRY & BIOLOGY

Phase I Trial of Bortezomib (PS-341; NSC 681239) and "Nonhybrid" (Bolus) Infusion Schedule of Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-cell Neoplasms

(2014) B. Holkova et al.   CLINICAL CANCER RESEARCH

Antagonists of IAP Proteins: Novel Anti-Tumor Agents

(2014) Yichao Wan et al.   CURRENT MEDICINAL CHEMISTRY

Structure-Guided Design and Optimization of Small Molecules Targeting the Protein–Protein Interaction between the von Hippel–Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor (HIF) Alpha Subunit with in Vitro Nanomolar Affinities

(2014) Carles Galdeano et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Novel CDK9 Inhibitor Shows Potent Antitumor Efficacy in Preclinical Hematologic Tumor Models

(2014) T. Yin et al.   MOLECULAR CANCER THERAPEUTICS

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

(2014) Eric S. Fischer et al.   NATURE

Resistance Mechanisms for the Bruton's Tyrosine Kinase Inhibitor Ibrutinib

(2014) Jennifer A. Woyach et al.   NEW ENGLAND JOURNAL OF MEDICINE

First-Line Crizotinib versus Chemotherapy in ALK-Positive Lung Cancer

(2014) Benjamin J. Solomon et al.   NEW ENGLAND JOURNAL OF MEDICINE

Ceritinib in ALK-Rearranged Non–Small-Cell Lung Cancer

(2014)   NEW ENGLAND JOURNAL OF MEDICINE

Cancer cell death induced by novel small molecules degrading the TACC3 protein via the ubiquitin–proteasome pathway

(2014) N Ohoka et al.   Cell Death & Disease

Readout of Epigenetic Modifications

(2013) Dinshaw J. Patel et al.   Annual Review of Biochemistry

The two faces of Cdk8, a positive/negative regulator of transcription

(2013) Josipa Nemet et al.   BIOCHIMIE

Development of hybrid small molecules that induce degradation of estrogen receptor-alpha and necrotic cell death in breast cancer cells

(2013) Keiichiro Okuhira et al.   CANCER SCIENCE

Cdks, cyclins and CKIs: roles beyond cell cycle regulation

(2013) S. Lim et al.   DEVELOPMENT

Targeted cancer therapy – Are the days of systemic chemotherapy numbered?

(2013) Won Duk Joo et al.   MATURITAS

A Novel Small-Molecule Inhibitor of Mcl-1 Blocks Pancreatic Cancer Growth In Vitro and In Vivo

(2013) F. Abulwerdi et al.   MOLECULAR CANCER THERAPEUTICS

Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy

(2013) Peter E. Czabotar et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

BET Inhibition Silences Expression of MYCN and BCL2 and Induces Cytotoxicity in Neuroblastoma Tumor Models

(2013) Anastasia Wyce et al.   PLoS One

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

(2013) J. Kronke et al.   SCIENCE

The Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins

(2013) G. Lu et al.   SCIENCE

Small-Molecule Inhibitors of the Interaction between the E3 Ligase VHL and HIF1α

(2012) Dennis L. Buckley et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Upregulation of CRABP1 in human neuroblastoma cells overproducing the Alzheimer-typical Aβ42reduces their differentiation potential

(2012) Markus Uhrig et al.   BMC Medicine

Dissecting Fragment-Based Lead Discovery at the von Hippel-Lindau Protein:Hypoxia Inducible Factor 1α Protein-Protein Interface

(2012) Inge Van Molle et al.   CHEMISTRY & BIOLOGY

BET bromodomain inhibition as a novel strategy for reactivation of HIV-1

(2012) Camellia Banerjee et al.   JOURNAL OF LEUKOCYTE BIOLOGY

Selective Histone Deacetylase 6 Inhibitors Bearing Substituted Urea Linkers Inhibit Melanoma Cell Growth

(2012) Joel A. Bergman et al.   JOURNAL OF MEDICINAL CHEMISTRY

Targeting the von Hippel–Lindau E3 Ubiquitin Ligase Using Small Molecules To Disrupt the VHL/HIF-1α Interaction

(2012) Dennis L. Buckley et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Targeting IAP proteins for therapeutic intervention in cancer

(2012) Simone Fulda et al.   NATURE REVIEWS DRUG DISCOVERY

Bcl-xL-inhibitory BH3 mimetics can induce a transient thrombocytopathy that undermines the hemostatic function of platelets

(2011) S. M. Schoenwaelder et al.   BLOOD

BET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc

(2011) Jake E. Delmore et al.   CELL

3-Thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (S1) Based Molecules as Potent, Dual Inhibitors of B-Cell Lymphoma 2 (Bcl-2) and Myeloid Cell Leukemia Sequence 1 (Mcl-1): Structure-Based Design and Structure−Activity Relationship Studies

(2011) Zhichao Zhang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Estrogen related receptors (ERRs): A new dawn in transcriptional control of mitochondrial gene networks

(2011) Lillian J. Eichner et al.   MITOCHONDRION

Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia

(2011) Mark A. Dawson et al.   NATURE

Homoharringtonine reduced Mcl-1 expression and induced apoptosis in chronic lymphocytic leukemia

(2010) R. Chen et al.   BLOOD

Protein Knockdown Using Methyl Bestatin−Ligand Hybrid Molecules: Design and Synthesis of Inducers of Ubiquitination-Mediated Degradation of Cellular Retinoic Acid-Binding Proteins

(2010) Yukihiro Itoh et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Renal cell carcinoma with novel VCL–ALK fusion: new representative of ALK-associated tumor spectrum

(2010) Larisa V Debelenko et al.   MODERN PATHOLOGY

Impact of linker length on the activity of PROTACs

(2010) Kedra Cyrus et al.   Molecular BioSystems

Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma

(2010) R. Eric Davis et al.   NATURE

Suppression of inflammation by a synthetic histone mimic

(2010) Edwige Nicodeme et al.   NATURE

The landscape of somatic copy-number alteration across human cancers

(2010) Rameen Beroukhim et al.   NATURE

Selective inhibition of BET bromodomains

(2010) Panagis Filippakopoulos et al.   NATURE

Mitochondria and cell death: outer membrane permeabilization and beyond

(2010) Stephen W. G. Tait et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

EML4-ALK Mutations in Lung Cancer That Confer Resistance to ALK Inhibitors

(2010) Young Lim Choi et al.   NEW ENGLAND JOURNAL OF MEDICINE

Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer

(2010) Eunice L. Kwak et al.   NEW ENGLAND JOURNAL OF MEDICINE

Identification of a Primary Target of Thalidomide Teratogenicity

(2010) T. Ito et al.   SCIENCE

Targeted intracellular protein degradation induced by a small molecule: En route to chemical proteomics

(2008) Ashley R. Schneekloth et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Transcriptional Control of Energy Homeostasis by the Estrogen-Related Receptors

(2008) Vincent Giguère   ENDOCRINE REVIEWS

Regulation of CRABP-II expression by MycN in Wilms tumor

(2008) Anu Gupta et al.   EXPERIMENTAL CELL RESEARCH

Small Molecules Destabilize cIAP1 by Activating Auto-ubiquitylation

(2008) Keiko Sekine et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Identification of ALK as a major familial neuroblastoma predisposition gene

(2008) Yaël P. Mossé et al.   NATURE

Oncogenic mutations of ALK kinase in neuroblastoma

(2008) Yuyan Chen et al.   NATURE

Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma

(2008) Isabelle Janoueix-Lerosey et al.   NATURE

Genome-Wide and Functional Annotation of Human E3 Ubiquitin Ligases Identifies MULAN, a Mitochondrial E3 that Regulates the Organelle's Dynamics and Signaling

(2008) Wei Li et al.   PLoS One