Impact of a five-dimensional framework on R&D productivity at AstraZeneca

Biomarker-Based Phase II Trial of Savolitinib in Patients With Advanced Papillary Renal Cell Cancer

(2017) Toni K. Choueiri et al.   JOURNAL OF CLINICAL ONCOLOGY

PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project

(2017) Fred R. Hirsch et al.   Journal of Thoracic Oncology

Structural insight into allosteric modulation of protease-activated receptor 2

(2017) Robert K. Y. Cheng et al.   NATURE

The chemical evolution of oligonucleotide therapies of clinical utility

(2017) Anastasia Khvorova et al.   NATURE BIOTECHNOLOGY

Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease

(2017) Frederick E. Dewey et al.   NEW ENGLAND JOURNAL OF MEDICINE

Targeting KRAS-dependent tumors with AZD4785, a high-affinity therapeutic antisense oligonucleotide inhibitor of KRAS

(2017) Sarah J. Ross et al.   Science Translational Medicine

Prothrombin time is predictive of low plasma prothrombin concentration and clinical outcome in patients with trauma hemorrhage: analyses of prospective observational cohort studies

(2017) Clare A. Balendran et al.   Scandinavian Journal of Trauma Resuscitation & Emergency Medicine

Small-Molecule PROTACS: New Approaches to Protein Degradation

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

Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity

(2016) P. Ballard et al.   CLINICAL CANCER RESEARCH

Secondary pharmacology: screening and interpretation of off-target activities – focus on translation

(2016) Steven Whitebread et al.   DRUG DISCOVERY TODAY

An analytical comparison between point-of-care uric acid testing meters

(2016) Jonathan Paraskos et al.   EXPERT REVIEW OF MOLECULAR DIAGNOSTICS

Chemical Space of DNA-Encoded Libraries

(2016) Raphael M. Franzini et al.   JOURNAL OF MEDICINAL CHEMISTRY

Optimization of a Series of Bivalent Triazolopyridazine Based Bromodomain and Extraterminal Inhibitors: The Discovery of (3R)-4-[2-[4-[1-(3-Methoxy-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-4-piperidyl]phenoxy]ethyl]-1,3-dimethyl-piperazin-2-one (AZD5153)

(2016) Robert H. Bradbury et al.   JOURNAL OF MEDICINAL CHEMISTRY

Potent and Selective Inhibitors of MTH1 Probe Its Role in Cancer Cell Survival

(2016) Jason G. Kettle et al.   JOURNAL OF MEDICINAL CHEMISTRY

134O_PR: Plasma ctDNA analysis for detection of EGFR T790M mutation in patients (pts) with EGFR mutation-positive advanced non-small cell lung cancer (aNSCLC)

(2016) S. Jenkins et al.   Journal of Thoracic Oncology

Irreversible Inhibition of EGFR: Modeling the Combined Pharmacokinetic-Pharmacodynamic Relationship of Osimertinib and Its Active Metabolite AZ5104

(2016) J. W. T. Yates et al.   MOLECULAR CANCER THERAPEUTICS

AZD5153: A Novel Bivalent BET Bromodomain Inhibitor Highly Active against Hematologic Malignancies

(2016) G. W. Rhyasen et al.   MOLECULAR CANCER THERAPEUTICS

Use of HμREL Human Coculture System for Prediction of Intrinsic Clearance and Metabolite Formation for Slowly Metabolized Compounds

(2016) Ia Hultman et al.   MOLECULAR PHARMACEUTICS

Correction

(2016)   NATURE

Reducing the risk of failure: biomarker-guided trial design

(2016) Michael J. Townsend et al.   NATURE REVIEWS DRUG DISCOVERY

Induced protein degradation: an emerging drug discovery paradigm

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

DNA-encoded chemistry: enabling the deeper sampling of chemical space

(2016) Robert A. Goodnow et al.   NATURE REVIEWS DRUG DISCOVERY

Direct small-molecule inhibitors of KRAS: from structural insights to mechanism-based design

(2016) Jonathan M. L. Ostrem et al.   NATURE REVIEWS DRUG DISCOVERY

Cornerstones of CRISPR–Cas in drug discovery and therapy

(2016) Christof Fellmann et al.   NATURE REVIEWS DRUG DISCOVERY

Twenty years on: the impact of fragments on drug discovery

(2016) Daniel A. Erlanson et al.   NATURE REVIEWS DRUG DISCOVERY

Pluripotent stem cells in disease modelling and drug discovery

(2016) Yishai Avior et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Adjunctive Lanicemine (AZD6765) in Patients with Major Depressive Disorder and History of Inadequate Response to Antidepressants: A Randomized, Placebo-Controlled Study

(2016) Gerard Sanacora et al.   NEUROPSYCHOPHARMACOLOGY

Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer

(2016) Martin Reck et al.   NEW ENGLAND JOURNAL OF MEDICINE

Decision-making in early clinical drug development

(2016) Paul Frewer et al.   PHARMACEUTICAL STATISTICS

Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism

(2016) P. Lito et al.   SCIENCE

Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action

(2016) Y. Pommier et al.   Science Translational Medicine

Selective Inhibition of Oncogenic KRAS Output with Small Molecules Targeting the Inactive State

(2016) M. P. Patricelli et al.   Cancer Discovery

Proteomic profiling of small-molecule inhibitors reveals dispensability of MTH1 for cancer cell survival

(2016) Tatsuro Kawamura et al.   Scientific Reports

Peripheral blood eosinophils: a surrogate marker for airway eosinophilia in stable COPD

(2016) Netsanet Negewo et al.   International Journal of Chronic Obstructive Pulmonary Disease

Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials

(2016) Nicola A Hanania et al.   Lancet Respiratory Medicine

Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies

(2016) Hector G Ortega et al.   Lancet Respiratory Medicine

Bromodomain inhibitor OTX015 in patients with lymphoma or multiple myeloma: a dose-escalation, open-label, pharmacokinetic, phase 1 study

(2016) Sandy Amorim et al.   Lancet Haematology

When Quality Beats Quantity: Decision Theory, Drug Discovery, and the Reproducibility Crisis

(2016) Jack W. Scannell et al.   PLoS One

Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs

(2016) Carlota Oleaga et al.   Scientific Reports

High throughput screening technologies for ion channels

(2015) Hai-bo Yu et al.   ACTA PHARMACOLOGICA SINICA

Abstract 3650: Discovery of the clinical candidate AZD9496: a potent and orally bioavailable selective estrogen receptor downregulator and antagonist:

(2015) Chris De Savi et al.   CANCER RESEARCH

Acquired Resistance to the Mutant-Selective EGFR Inhibitor AZD9291 Is Associated with Increased Dependence on RAS Signaling in Preclinical Models

(2015) C. A. Eberlein et al.   CANCER RESEARCH

Biological effects and clinical efficacy of a topical Toll-like receptor 7 agonist in seasonal allergic rhinitis: a parallel group controlled phase IIa study

(2015) Lennart Greiff et al.   INFLAMMATION RESEARCH

AZD3514, an oral selective androgen receptor down-regulator in patients with castration-resistant prostate cancer – results of two parallel first-in-human phase I studies

(2015) A. Omlin et al.   INVESTIGATIONAL NEW DRUGS

Small Molecule Binding Sites on the Ras:SOS Complex Can Be Exploited for Inhibition of Ras Activation

(2015) Jon J. G. Winter et al.   JOURNAL OF MEDICINAL CHEMISTRY

How Beyond Rule of 5 Drugs and Clinical Candidates Bind to Their Targets

(2015) Bradley C. Doak et al.   JOURNAL OF MEDICINAL CHEMISTRY

Prospective Predictions of Human Pharmacokinetics for Eighteen Compounds

(2015) Tao Zhang et al.   JOURNAL OF PHARMACEUTICAL SCIENCES

A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents

(2015) Ilka Maschmeyer et al.   LAB ON A CHIP

The DNA of a nation

(2015) Vivien Marx   NATURE

Know your target, know your molecule

(2015) Mark E Bunnage et al.   Nature Chemical Biology

The support of human genetic evidence for approved drug indications

(2015) Matthew R Nelson et al.   NATURE GENETICS

Acquired EGFR C797S mutation mediates resistance to AZD9291 in non–small cell lung cancer harboring EGFR T790M

(2015) Kenneth S Thress et al.   NATURE MEDICINE

Why is it hard to terminate failing projects in pharmaceutical R&D?

(2015) Richard W. Peck et al.   NATURE REVIEWS DRUG DISCOVERY

Towards a hit for every target

(2015) Steve Rees et al.   NATURE REVIEWS DRUG DISCOVERY

AZD9291 in EGFR Inhibitor–Resistant Non–Small-Cell Lung Cancer

(2015) Pasi A. Jänne et al.   NEW ENGLAND JOURNAL OF MEDICINE

DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer

(2015) Joaquin Mateo et al.   NEW ENGLAND JOURNAL OF MEDICINE

Factors influencing quality decision-making: regulatory and pharmaceutical industry perspectives

(2015) Ronan Donelan et al.   PHARMACOEPIDEMIOLOGY AND DRUG SAFETY

Lebrikizumab in moderate-to-severe asthma: pooled data from two randomised placebo-controlled studies

(2015) Nicola A Hanania et al.   THORAX

Abstract 5314: A proteomic signature predicts response to a therapeutic vaccine in pancreas cancer; analysis from the GI-4000-02 trial

(2015) Donald A. Richards et al.   CANCER RESEARCH

Abstract 3676: Influence of early toxicology assessment on the selection of azd9291

(2015) Mark J. Anderton et al.   CANCER RESEARCH

Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers

(2015) Luisa Carbognin et al.   PLoS One

Abstract LB-66: Results of two phase I multicenter trials of AZD5363, an inhibitor of AKT1, 2 and 3: Biomarker and early clinical evaluation in Western and Japanese patients with advanced solid tumors .

(2014) Udai Banerji et al.   CANCER RESEARCH

Development and Applications of CRISPR-Cas9 for Genome Engineering

(2014) Patrick D. Hsu et al.   CELL

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

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

The rise of systems pharmacology in drug discovery and development

(2014) Neil Benson et al.   Future Medicinal Chemistry

Discovery of a Potent and Selective EGFR Inhibitor (AZD9291) of Both Sensitizing and T790M Resistance Mutations That Spares the Wild Type Form of the Receptor

(2014) M. Raymond V. Finlay et al.   JOURNAL OF MEDICINAL CHEMISTRY

Biology-Oriented Synthesis: Harnessing the Power of Evolution

(2014) Hilde van Hattum et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Human biological sample biobanking to support tissue biomarkers in pharmaceutical research and development

(2014) Christopher Womack et al.   METHODS

Microfluidic organs-on-chips

(2014) Sangeeta N Bhatia et al.   NATURE BIOTECHNOLOGY

A decade of innovation in pharmaceutical R&D: the Chorus model

(2014) Paul K. Owens et al.   NATURE REVIEWS DRUG DISCOVERY

Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework

(2014) David Cook et al.   NATURE REVIEWS DRUG DISCOVERY

Drugging the undruggable RAS: Mission Possible?

(2014) Adrienne D. Cox et al.   NATURE REVIEWS DRUG DISCOVERY

Target organ profiles in toxicity studies supporting human dosing: An assessment of recovery and chronic dosing

(2014) Steve Horner et al.   REGULATORY TOXICOLOGY AND PHARMACOLOGY

Assessment of Cardiomyocyte Contraction in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes

(2014) Amy Pointon et al.   TOXICOLOGICAL SCIENCES

Bromodomain and extraterminal (BET) domain inhibitors induce a loss of intestinal stem cells and villous atrophy

(2014) Matt Wagoner et al.   TOXICOLOGY LETTERS

AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer

(2014) D. A. E. Cross et al.   Cancer Discovery

Benralizumab, an anti-interleukin 5 receptor α monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study

(2014) Mario Castro et al.   Lancet Respiratory Medicine

Model-based drug discovery: implementation and impact

(2013) Sandra A.G. Visser et al.   DRUG DISCOVERY TODAY

Exploratory toxicology as an integrated part of drug discovery. Part I: Why and how

(2013) Jorrit J. Hornberg et al.   DRUG DISCOVERY TODAY

Efficacy and tolerability of flexibly-dosed adjunct TC-5214 (dexmecamylamine) in patients with major depressive disorder and inadequate response to prior antidepressant

(2013) Eduard Vieta et al.   EUROPEAN NEUROPSYCHOPHARMACOLOGY

Evolution of ADME Science: Where Else Can Modeling and Simulation Contribute?

(2013) Dennis A. Smith   MOLECULAR PHARMACEUTICS

Development of PI3K inhibitors: lessons learned from early clinical trials

(2013) Jordi Rodon et al.   Nature Reviews Clinical Oncology

Does size matter in R&D productivity? If not, what does?

(2013) Michael Ringel et al.   NATURE REVIEWS DRUG DISCOVERY

Targeting eosinophils in allergy, inflammation and beyond

(2013) Patricia C. Fulkerson et al.   NATURE REVIEWS DRUG DISCOVERY

European Lead Factory opens for business

(2013) Asher Mullard   NATURE REVIEWS DRUG DISCOVERY

Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay

(2013) D. M. Molina et al.   SCIENCE

Biomarkers of Response to Akt Inhibitor MK-2206 in Breast Cancer

(2012) T. Sangai et al.   CLINICAL CANCER RESEARCH

Big pharma screening collections: more of the same or unique libraries? The AstraZeneca–Bayer Pharma AG case

(2012) Thierry Kogej et al.   DRUG DISCOVERY TODAY

The right compound in the right assay at the right time: an integrated discovery DMPK strategy

(2012) Peter Ballard et al.   DRUG METABOLISM REVIEWS

Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study

(2012) Pasi A Jänne et al.   LANCET ONCOLOGY

Application of In Silico, In Vitro and Preclinical Pharmacokinetic Data for the Effective and Efficient Prediction of Human Pharmacokinetics

(2012) Kenneth H. Grime et al.   MOLECULAR PHARMACEUTICS

MET: a promising anticancer therapeutic target

(2012) Solange Peters et al.   Nature Reviews Clinical Oncology

Diagnosing the decline in pharmaceutical R&D efficiency

(2012) Jack W. Scannell et al.   NATURE REVIEWS DRUG DISCOVERY

Application of Optical Biosensors in Small-Molecule Screening Activities

(2012) Stefan Geschwindner et al.   SENSORS

Chemoproteomic approaches to drug target identification and drug profiling

(2011) Marcus Bantscheff et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Prediction of Human Oral Plasma Concentration-Time Profiles Using Preclinical Data

(2011) An Van den Bergh et al.   CLINICAL PHARMACOKINETICS

Simulation of Human Intravenous and Oral Pharmacokinetics of 21 Diverse Compounds Using Physiologically Based Pharmacokinetic Modelling

(2011) Hannah M. Jones et al.   CLINICAL PHARMACOKINETICS

The Innate Immune Response, Clinical Outcomes, and Ex Vivo HCV Antiviral Efficacy of a TLR7 Agonist (PF-4878691)

(2011) M D Fidock et al.   CLINICAL PHARMACOLOGY & THERAPEUTICS

Can the flow of medicines be improved? Fundamental pharmacokinetic and pharmacological principles toward improving Phase II survival

(2011) Paul Morgan et al.   DRUG DISCOVERY TODAY

How were new medicines discovered?

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

Trends in the exploitation of novel drug targets

(2011) Mathias Rask-Andersen et al.   NATURE REVIEWS DRUG DISCOVERY

A TALE nuclease architecture for efficient genome editing

(2010) Jeffrey C Miller et al.   NATURE BIOTECHNOLOGY

How to improve R&D productivity: the pharmaceutical industry's grand challenge

(2010) Steven M. Paul et al.   NATURE REVIEWS DRUG DISCOVERY

The properties of thermostabilised G protein-coupled receptors (StaRs) and their use in drug discovery

(2010) Nathan Robertson et al.   NEUROPHARMACOLOGY

Escape from Flatland: Increasing Saturation as an Approach to Improving Clinical Success

(2009) Frank Lovering et al.   JOURNAL OF MEDICINAL CHEMISTRY

Recent Advances in High Throughput Screening for ADME Properties

(2008) Timothy Carlson et al.   COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING

The exploration of macrocycles for drug discovery — an underexploited structural class

(2008) Edward M. Driggers et al.   NATURE REVIEWS DRUG DISCOVERY