Introduction to biological complexity as a missing link in drug discovery

The immature electrophysiological phenotype of iPSC-CMs still hampers in vitro drug screening: Special focus on I K1

(2018) Birgit Goversen et al.   PHARMACOLOGY & THERAPEUTICS

The role of declining adaptive homeostasis in ageing

(2017) Laura C. D. Pomatto et al.   JOURNAL OF PHYSIOLOGY-LONDON

Extensive Homeostatic T Cell Phenotypic Variation within the Collaborative Cross

(2017) Jessica B. Graham et al.   Cell Reports

Non-invasive cardiovascular imaging for evaluating subclinical target organ damage in hypertensive patients

(2017) Pasquale Perrone-Filardi et al.   European Heart Journal-Cardiovascular Imaging

Machine Learning of Human Pluripotent Stem Cell-Derived Engineered Cardiac Tissue Contractility for Automated Drug Classification

(2017) Eugene K. Lee et al.   Stem Cell Reports

Cardiomyocytes from human pluripotent stem cells: From laboratory curiosity to industrial biomedical platform

(2016) Chris Denning et al.   BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

The Fallacy of Assigning Chamber Specificity to iPSC Cardiac Myocytes from Action Potential Morphology

(2016) Christopher Kane et al.   BIOPHYSICAL JOURNAL

Effect of flecainide derivatives on sarcoplasmic reticulum calcium release suggests a lack of direct action on the cardiac ryanodine receptor

(2016) Mark L Bannister et al.   BRITISH JOURNAL OF PHARMACOLOGY

Pleiotropic mechanisms of action of perhexiline in heart failure

(2016) Christopher H. George et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

Stem cell-derived models to improve mechanistic understanding and prediction of human drug-induced liver injury

(2016) Christopher Goldring et al.   HEPATOLOGY

Questioning flecainide's mechanism of action in the treatment of catecholaminergic polymorphic ventricular tachycardia

(2016) Alan J. Williams et al.   JOURNAL OF PHYSIOLOGY-LONDON

Evolution of strategies to improve preclinical cardiac safety testing

(2016) Gary Gintant et al.   NATURE REVIEWS DRUG DISCOVERY

The Mechanism of Flecainide Action in CPVT Does Not Involve a Direct Effect on RyR2

(2015) M. L. Bannister et al.   CIRCULATION RESEARCH

Using quantitative systems pharmacology for novel drug discovery

(2015) Violeta I Pérez-Nueno   Expert Opinion on Drug Discovery

Lessons learned from multi-scale modeling of the failing heart

(2015) Juan F. Gomez et al.   JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY

In silicoprediction of drug therapy in catecholaminergic polymorphic ventricular tachycardia

(2015) Pei-Chi Yang et al.   JOURNAL OF PHYSIOLOGY-LONDON

Every Cell Is Special: Genome-wide Studies Add a New Dimension to Single-Cell Biology

(2014) Jan Philipp Junker et al.   CELL

The value of translational biomarkers to phenotypic assays

(2014) David C. Swinney   Frontiers in Pharmacology

Triple mode of action of flecainide in catecholaminergic polymorphic ventricular tachycardia

(2013) D. S. Steele et al.   CARDIOVASCULAR RESEARCH

Triple mode of action of flecainide in catecholaminergic polymorphic ventricular tachycardia: reply

(2013) M. B. Sikkel et al.   CARDIOVASCULAR RESEARCH

Flecainide reduces Ca2+ spark and wave frequency via inhibition of the sarcolemmal sodium current

(2013) Markus B. Sikkel et al.   CARDIOVASCULAR RESEARCH

Troubleshooting and deconvoluting label-free cell phenotypic assays in drug discovery

(2013) Ye Fang   JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS

A network-oriented perspective on cardiac calcium signaling

(2012) Christopher H. George et al.   AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY

Ranolazine stabilizes cardiac ryanodine receptors: A novel mechanism for the suppression of early afterdepolarization and torsades de pointes in long QT type 2

(2012) Ashish Parikh et al.   HEART RHYTHM

Exploiting mathematical models to illuminate electrophysiological variability between individuals

(2012) Amrita X. Sarkar et al.   JOURNAL OF PHYSIOLOGY-LONDON

Interpreting noncoding genetic variation in complex traits and human disease

(2012) Lucas D Ward et al.   NATURE BIOTECHNOLOGY

iPSC Disease Modeling

(2012) F. Soldner et al.   SCIENCE

Computational Approaches for Analyzing Information Flow in Biological Networks

(2012) B. Kholodenko et al.   Science Signaling

Non-Linear Dynamics of Cardiac Alternans: Subcellular to Tissue-Level Mechanisms of Arrhythmia

(2012) Stephen A. Gaeta et al.   Frontiers in Physiology

Cellular Decision Making and Biological Noise: From Microbes to Mammals

(2011) Gábor Balázsi et al.   CELL

Short Communication: Flecainide Exerts an Antiarrhythmic Effect in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia by Increasing the Threshold for Triggered Activity

(2011) Nian Liu et al.   CIRCULATION RESEARCH

Searching for new cardiovascular drugs: towards improved systems for drug screening?

(2011) Nicole C Silvester et al.   Expert Opinion on Drug Discovery

Electrophysiologic basis for the antiarrhythmic actions of ranolazine

(2011) Charles Antzelevitch et al.   HEART RHYTHM

Carnitine Palmitoyltransferase (CPT) Modulators: A Medicinal Chemistry Perspective on 35 Years of Research

(2011) Simona M. Ceccarelli et al.   JOURNAL OF MEDICINAL CHEMISTRY

Flecainide Therapy Reduces Exercise-Induced Ventricular Arrhythmias in Patients With Catecholaminergic Polymorphic Ventricular Tachycardia

(2011) Christian van der Werf et al.   JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

Cell-to-cell variability of alternative RNA splicing

(2011) Z. Waks et al.   Molecular Systems Biology

How were new medicines discovered?

(2011) David C. Swinney et al.   NATURE REVIEWS DRUG DISCOVERY

Genetic Variations Strongly Influence Phenotypic Outcome in the Mouse Retina

(2011) Austin S. Jelcick et al.   PLoS One

Functional Selectivity and Biased Receptor Signaling

(2010) T. Kenakin   JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS

Complex networks: The fragility of interdependency

(2010) Alessandro Vespignani   NATURE

Not all noise is waste

(2010) Vito Quaranta et al.   NATURE METHODS

Network medicine: a network-based approach to human disease

(2010) Albert-László Barabási et al.   NATURE REVIEWS GENETICS

Systematizing Serendipity for Cardiovascular Drug Discovery

(2009) Peter J. Schlueter et al.   CIRCULATION

Flecainide inhibits arrhythmogenic Ca2+ waves by open state block of ryanodine receptor Ca2+ release channels and reduction of Ca2+ spark mass

(2009) Fredrick A. Hilliard et al.   JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY

Temporal switching and cell-to-cell variability in Ca2+ release activity in mammalian cells

(2009) Naotoshi Nakamura et al.   Molecular Systems Biology

Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in mice and humans

(2009) Hiroshi Watanabe et al.   NATURE MEDICINE