Epigenetic polypharmacology: from combination therapy to multitargeted drugs

Multitarget Drugs: an Epigenetic Epiphany

(2016) A. Ganesan   ChemMedChem

Design, synthesis and biological evaluation of N-phenylquinazolin-4-amine hybrids as dual inhibitors of VEGFR-2 and HDAC

(2016) Fan-Wei Peng et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Transition state for the NSD2-catalyzed methylation of histone H3 lysine 36

(2016) Myles B. Poulin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Phase I study evaluating the safety and efficacy of oral panobinostat in combination with radiotherapy or chemoradiotherapy in patients with inoperable stage III non-small-cell lung cancer

(2015) Harminder S. Takhar et al.   ANTI-CANCER DRUGS

KDM1 class flavin-dependent protein lysine demethylases

(2015) Jonathan M. Burg et al.   BIOPOLYMERS

BET Inhibition Upregulates SIRT1 and Alleviates Inflammatory Responses

(2015) Tarja Kokkola et al.   CHEMBIOCHEM

Discovery of Chemical Inhibitors of Human Bromodomains

(2015) Guangtao Zhang et al.   CHEMICAL REVIEWS

Hijacking the E3 Ubiquitin Ligase Cereblon to Efficiently Target BRD4

(2015) Jing Lu et al.   CHEMISTRY & BIOLOGY

Hybrids from Farnesylthiosalicylic Acid and Hydroxamic Acid as Dual Ras-Related Signaling and Histone Deacetylase (HDAC) Inhibitors: Design, Synthesis and Biological Evaluation

(2015) Yong Ling et al.   ChemMedChem

A Phase I Study of CUDC-101, a Multitarget Inhibitor of HDACs, EGFR, and HER2, in Combination with Chemoradiation in Patients with Head and Neck Squamous Cell Carcinoma

(2015) T. J. Galloway et al.   CLINICAL CANCER RESEARCH

A DNA/HDAC dual-targeting drug CY190602 with significantly enhanced anticancer potency

(2015) C. Liu et al.   EMBO Molecular Medicine

Design, synthesis and biological evaluation of colchicine derivatives as novel tubulin and histone deacetylase dual inhibitors

(2015) Xuan Zhang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

First-in-human study of the toxicity, pharmacokinetics, and pharmacodynamics of CG200745, a pan-HDAC inhibitor, in patients with refractory solid malignancies

(2015) Kyu-pyo Kim et al.   INVESTIGATIONAL NEW DRUGS

Dual-Mode HDAC Prodrug for Covalent Modification and Subsequent Inhibitor Release

(2015) Kevin B. Daniel et al.   JOURNAL OF MEDICINAL CHEMISTRY

Novel Bioactive Hybrid Compound Dual Targeting Estrogen Receptor and Histone Deacetylase for the Treatment of Breast Cancer

(2015) Chu Tang et al.   JOURNAL OF MEDICINAL CHEMISTRY

EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumours to TopoII inhibitors

(2015) Christine M. Fillmore et al.   NATURE

Transcriptional plasticity promotes primary and acquired resistance to BET inhibition

(2015) Philipp Rathert et al.   NATURE

BET inhibitor resistance emerges from leukaemia stem cells

(2015) Chun Yew Fong et al.   NATURE

DOT1L inhibits SIRT1-mediated epigenetic silencing to maintain leukemic gene expression in MLL-rearranged leukemia

(2015) Chun-Wei Chen et al.   NATURE MEDICINE

Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma

(2015) Pawel K Mazur et al.   NATURE MEDICINE

Preclinical activity of combined HDAC and KDM1A inhibition in glioblastoma

(2015) Melissa M. Singh et al.   NEURO-ONCOLOGY

Phthalimide conjugation as a strategy for in vivo target protein degradation

(2015) G. E. Winter et al.   SCIENCE

Fragments in bromodomain drug discovery

(2015) Paul Bamborough et al.   MedChemComm

Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer

(2015) Jason S. Kirk et al.   Oncotarget

Suberoylanilide hydroxamic acid (SAHA) and cladribine synergistically induce apoptosis in NK-LGL leukaemia

(2014) Xiaoshen Sun et al.   BRITISH JOURNAL OF HAEMATOLOGY

Bromodomains and Their Pharmacological Inhibitors

(2014) Daniel Gallenkamp et al.   ChemMedChem

The combination of irreversible EGFR TKIs and SAHA induces apoptosis and autophagy-mediated cell death to overcome acquired resistance in EGFRT790M-mutated lung cancer

(2014) Tae-Gul Lee et al.   INTERNATIONAL JOURNAL OF CANCER

Polypharmacology: Challenges and Opportunities in Drug Discovery

(2014) Andrew Anighoro et al.   JOURNAL OF MEDICINAL CHEMISTRY

Inhibition and Mechanism of HDAC8 Revisited

(2014) Kai Chen et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia

(2014) Birgit Knoechel et al.   NATURE GENETICS

Synthesis of hybrid anticancer agents based on kinase and histone deacetylase inhibitors

(2014) Hiren Patel et al.   MedChemComm

The structure based design of dual HDAC/BET inhibitors as novel epigenetic probes

(2014) Stephen J. Atkinson et al.   MedChemComm

Epigenetic therapy of acute myeloid leukemia using 5-aza-2'-deoxycytidine (decitabine) in combination with inhibitors of histone methylation and deacetylation

(2014) Richard L Momparler et al.   Clinical Epigenetics

Selectively Targeting Prostate Cancer with Antiandrogen Equipped Histone Deacetylase Inhibitors

(2013) Berkley E. Gryder et al.   ACS Chemical Biology

Discovery of a small molecular compound simultaneously targeting RXR and HADC: Design, synthesis, molecular docking and bioassay

(2013) Guo-Liang Chen et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

BET Bromodomains Mediate Transcriptional Pause Release in Heart Failure

(2013) Priti Anand et al.   CELL

Effects of treatment with histone deacetylase inhibitors in solid tumors: a review based on 30 clinical trials

(2013) Tianzhu Qiu et al.   Future Oncology

BET bromodomain inhibition suppresses TH17-mediated pathology

(2013) Deanna A. Mele et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Design and Synthesis of Dual-Action Inhibitors Targeting Histone Deacetylases and 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase for Cancer Treatment

(2013) Jhih-Bin Chen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Pan-Histone Demethylase Inhibitors Simultaneously Targeting Jumonji C and Lysine-Specific Demethylases Display High Anticancer Activities

(2013) Dante Rotili et al.   JOURNAL OF MEDICINAL CHEMISTRY

The HDAC inhibitor, MPT0E028, enhances erlotinib-induced cell death in EGFR-TKI-resistant NSCLC cells

(2013) M-C Chen et al.   Cell Death & Disease

Synthesis and Biological Evaluation of the First Example of NO-Donor Histone Deacetylase Inhibitor

(2013) Emily Borretto et al.   ACS Medicinal Chemistry Letters

Synthesis and biological evaluation of N-aryl salicylamides with a hydroxamic acid moiety at 5-position as novel HDAC–EGFR dual inhibitors

(2012) Miao Zuo et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Epigenetic Resensitization to Platinum in Ovarian Cancer

(2012) D. Matei et al.   CANCER RESEARCH

Synthetically Accessible Non-Secosteroidal Hybrid Molecules Combining Vitamin D Receptor Agonism and Histone Deacetylase Inhibition

(2012) Joshua Fischer et al.   CHEMISTRY & BIOLOGY

Cancer Network Disruption by a Single Molecule Inhibitor Targeting Both Histone Deacetylase Activity and Phosphatidylinositol 3-Kinase Signaling

(2012) C. Qian et al.   CLINICAL CANCER RESEARCH

Dual Targeting of Histone Deacetylase and Topoisomerase II with Novel Bifunctional Inhibitors

(2012) William Guerrant et al.   JOURNAL OF MEDICINAL CHEMISTRY

Indole-Derived Psammaplin A Analogues as Epigenetic Modulators with Multiple Inhibitory Activities

(2012) Raquel Pereira et al.   JOURNAL OF MEDICINAL CHEMISTRY

Combinatorial drug therapy for cancer in the post-genomic era

(2012) Bissan Al-Lazikani et al.   NATURE BIOTECHNOLOGY

Targeting Epigenetic Readers in Cancer

(2012) Mark A. Dawson et al.   NEW ENGLAND JOURNAL OF MEDICINE

Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors

(2012) H. S. Bandukwala et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Chimerically designed HDAC- and tyrosine kinase inhibitors. A series of erlotinib hybrids as dual-selective inhibitors of EGFR, HER2 and histone deacetylases

(2012) Thomas Beckers et al.   MedChemComm

A phase II study of the histone deacetylase inhibitor vorinostat combined with tamoxifen for the treatment of patients with hormone therapy-resistant breast cancer

(2011) P N Munster et al.   BRITISH JOURNAL OF CANCER

Phase I study of the histone deacetylase inhibitor entinostat in combination with 13-cis retinoic acid in patients with solid tumours

(2011) R Pili et al.   BRITISH JOURNAL OF CANCER

Epigenetic Multiple Modulators

(2011) Rosana Alvarez et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

Rational therapeutic combinations with histone deacetylase inhibitors for the treatment of cancer

(2011) K Ted Thurn et al.   Future Oncology

RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia

(2011) Johannes Zuber et al.   NATURE

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

(2011) Mark A. Dawson et al.   NATURE

Combination Epigenetic Therapy Has Efficacy in Patients with Refractory Advanced Non-Small Cell Lung Cancer

(2011) R. A. Juergens et al.   Cancer Discovery

Vorinostat and Sorafenib Increase CD95 Activation in Gastrointestinal Tumor Cells through a Ca2+-De novo Ceramide-PP2A-Reactive Oxygen Species-Dependent Signaling Pathway

(2010) M. A. Park et al.   CANCER RESEARCH

Protein Dynamics in Drug Combinations: a Linear Superposition of Individual-Drug Responses

(2010) Naama Geva-Zatorsky et al.   CELL

Discovery of 7-(4-(3-Ethynylphenylamino)-7-methoxyquinazolin-6-yloxy)-N-hydroxyheptanamide (CUDC-101) as a Potent Multi-Acting HDAC, EGFR, and HER2 Inhibitor for the Treatment of Cancer

(2010) Xiong Cai et al.   JOURNAL OF MEDICINAL CHEMISTRY

Novel Chimeric Histone Deacetylase Inhibitors: A Series of Lapatinib Hybrides as Potent Inhibitors of Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and Histone Deacetylase Activity

(2010) Siavosh Mahboobi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Seeking the causes and solutions to imatinib-resistance in chronic myeloid leukemia

(2010) D Bixby et al.   LEUKEMIA

Suppression of inflammation by a synthetic histone mimic

(2010) Edwige Nicodeme et al.   NATURE

Selective inhibition of BET bromodomains

(2010) Panagis Filippakopoulos et al.   NATURE

Acetylation of Metabolic Enzymes Coordinates Carbon Source Utilization and Metabolic Flux

(2010) Q. Wang et al.   SCIENCE

Regulation of Cellular Metabolism by Protein Lysine Acetylation

(2010) S. Zhao et al.   SCIENCE

Histone deacetylase and microtubules as targets for the synthesis of releasable conjugate compounds

(2009) Daniele Passarella et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

HDACi – Targets beyond chromatin

(2009) Marc Buchwald et al.   CANCER LETTERS

Targeting DNA Methylation

(2009) J.-P. J. Issa et al.   CLINICAL CANCER RESEARCH

Drug Effects Viewed from a Signal Transduction Network Perspective

(2009) Anton F. Fliri et al.   JOURNAL OF MEDICINAL CHEMISTRY

Design of Chimeric Histone Deacetylase- and Tyrosine Kinase-Inhibitors: A Series of Imatinib Hybrides as Potent Inhibitors of Wild-Type and Mutant BCR-ABL, PDGF-Rβ, and Histone Deacetylases†

(2009) Siavosh Mahboobi et al.   JOURNAL OF MEDICINAL CHEMISTRY

Vorinostat and bortezomib exert synergistic antiproliferative and proapoptotic effects in colon cancer cell models

(2009) T. M. Pitts et al.   MOLECULAR CANCER THERAPEUTICS

Combinatorial pharmacologic approaches target EZH2-mediated gene repression in breast cancer cells

(2009) F. Sun et al.   MOLECULAR CANCER THERAPEUTICS

Recent progress in the biology and physiology of sirtuins

(2009) Toren Finkel et al.   NATURE

Predicting new molecular targets for known drugs

(2009) Michael J. Keiser et al.   NATURE

Protein methyltransferases as a target class for drug discovery

(2009) Robert A. Copeland et al.   NATURE REVIEWS DRUG DISCOVERY

Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions

(2009) C. Choudhary et al.   SCIENCE

Selective Inhibition of Histone Deacetylase 2 Silences Progesterone Receptor-Mediated Signaling

(2008) E. Bicaku et al.   CANCER RESEARCH

Mechanisms and Molecular Probes of Sirtuins

(2008) Brian C. Smith et al.   CHEMISTRY & BIOLOGY

A Phase II Trial of Vorinostat (Suberoylanilide Hydroxamic Acid) in Metastatic Breast Cancer: A California Cancer Consortium Study

(2008) T. H. Luu et al.   CLINICAL CANCER RESEARCH

The Structure and Function of Histone Deacetylases: The Target for Anti-cancer Therapy

(2008) Yingjie Zhang et al.   CURRENT MEDICINAL CHEMISTRY

The emerging functions of histone demethylases

(2008) Karl Agger et al.   CURRENT OPINION IN GENETICS & DEVELOPMENT

Epigenetic Multiple Ligands: Mixed Histone/Protein Methyltransferase, Acetyltransferase, and Class III Deacetylase (Sirtuin) Inhibitors

(2008) Antonello Mai et al.   JOURNAL OF MEDICINAL CHEMISTRY

Design, Synthesis, and Evaluation of Novel Mutual Prodrugs (Hybrid Drugs) of All-trans-Retinoic Acid and Histone Deacetylase Inhibitors with Enhanced Anticancer Activities in Breast and Prostate Cancer Cells in Vitro

(2008) Lalji K. Gediya et al.   JOURNAL OF MEDICINAL CHEMISTRY

Highly Dissociative and Concerted Mechanism for the Nicotinamide Cleavage Reaction in Sir2Tm Enzyme Suggested by Ab Initio QM/MM Molecular Dynamics Simulations

(2008) Po Hu et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Epigenetic interplay between histone modifications and DNA methylation in gene silencing

(2008) T VAISSIERE et al.   MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH

Double-edged swords as cancer therapeutics: simultaneously targeting p53 and NF-κB pathways

(2008) Anwesha Dey et al.   NATURE REVIEWS DRUG DISCOVERY

Structural Insights into Intermediate Steps in the Sir2 Deacetylation Reaction

(2008) William F. Hawse et al.   STRUCTURE

Hybrid Molecules with a Dual Mode of Action: Dream or Reality?†

(2007) Bernard Meunier   ACCOUNTS OF CHEMICAL RESEARCH