An αv-RGD Integrin Inhibitor Toolbox: Drug Discovery Insight, Challenges and Opportunities

Emergence of Small-Molecule Non-RGD-Mimetic Inhibitors for RGD Integrins

(2017) Lisa M. Miller et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Comprehensive Evaluation of the Activity and Selectivity Profile of Ligands for RGD-binding Integrins

(2017) Tobias G. Kapp et al.   Scientific Reports

Investigation of miscellaneous hERG inhibition in large diverse compound collection using automated patch-clamp assay

(2016) Hai-bo Yu et al.   ACTA PHARMACOLOGICA SINICA

In vitro cancer cell–ECM interactions inform in vivo cancer treatment

(2016) Andrew W. Holle et al.   ADVANCED DRUG DELIVERY REVIEWS

Arginine-Glycine-Aspartate–Binding Integrins as Therapeutic and Diagnostic Targets

(2016) Cui-Cui Sun et al.   AMERICAN JOURNAL OF THERAPEUTICS

Characterisation of a novel, high affinity and selective αvβ6 integrin RGD-mimetic radioligand

(2016) Eleanor R. Hall et al.   BIOCHEMICAL PHARMACOLOGY

αv integrins: key regulators of tissue fibrosis

(2016) Kylie P. Conroy et al.   CELL AND TISSUE RESEARCH

Differential Effect on Bone Lesions of Targeting Integrins: Randomized Phase II Trial of Abituzumab in Patients with Metastatic Castration-Resistant Prostate Cancer

(2016) M. Hussain et al.   CLINICAL CANCER RESEARCH

Minireview: Fibronectin in retinal disease

(2016) Charles G Miller et al.   EXPERIMENTAL BIOLOGY AND MEDICINE

Zwitterionic structures: from physicochemical properties toward computer-aided drug designs

(2016) Zhiwei Yang et al.   Future Medicinal Chemistry

A dose escalating phase I study of GLPG0187, a broad spectrum integrin receptor antagonist, in adult patients with progressive high-grade glioma and other advanced solid malignancies

(2016) Geert A. Cirkel et al.   INVESTIGATIONAL NEW DRUGS

NFκB-Induced Periostin Activates Integrin-β3 Signaling to Promote Renal Injury in GN

(2016) Niki Prakoura et al.   JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY

Integrin-based therapeutics: biological basis, clinical use and new drugs

(2016) Klaus Ley et al.   NATURE REVIEWS DRUG DISCOVERY

Phase II and phase III failures: 2013–2015

(2016) Richard K. Harrison   NATURE REVIEWS DRUG DISCOVERY

Synthesis and determination of absolute configuration of a non-peptidic αvβ6 integrin antagonist for the treatment of idiopathic pulmonary fibrosis

(2016) Niall A. Anderson et al.   ORGANIC & BIOMOLECULAR CHEMISTRY

Pharmacological Characterization of the αvβ6 Integrin Binding and Internalization Kinetics of the Foot-and-Mouth Disease Virus Derived Peptide A20FMDV2

(2016) Robert J. Slack et al.   PHARMACOLOGY

Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF

(2016) Paul F Mercer et al.   THORAX

Exploring N-Arylsulfonyl-l-proline Scaffold as a Platform for Potent and Selective αvβ1 Integrin Inhibitors

(2016) Nilgun Isik Reed et al.   ACS Medicinal Chemistry Letters

Small Cause, Great Impact: Modification of the Guanidine Group in the RGD Motif Controls Integrin Subtype Selectivity

(2015) Tobias G. Kapp et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Stable Peptides Instead of Stapled Peptides: Highly Potent αvβ6-Selective Integrin Ligands

(2015) Oleg V. Maltsev et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Integrin αvβ6 sets the stage for colorectal cancer metastasis

(2015) D. I. Cantor et al.   CANCER AND METASTASIS REVIEWS

The promise and peril of chemical probes

(2015) Cheryl H Arrowsmith et al.   Nature Chemical Biology

The support of human genetic evidence for approved drug indications

(2015) Matthew R Nelson et al.   NATURE GENETICS

New tools to target an elusive integrin

(2015) Katie Kingwell   NATURE REVIEWS DRUG DISCOVERY

Dissecting fibrosis: therapeutic insights from the small-molecule toolbox

(2015) Carmel B. Nanthakumar et al.   NATURE REVIEWS DRUG DISCOVERY

An analysis of the attrition of drug candidates from four major pharmaceutical companies

(2015) Michael J. Waring et al.   NATURE REVIEWS DRUG DISCOVERY

Orally active αvβ3 integrin inhibitor MK-0429 reduces melanoma metastasis

(2015) MAUREEN PICKARSKI et al.   ONCOLOGY REPORTS

Arginine: Its pKavalue revisited

(2015) Carolyn A. Fitch et al.   PROTEIN SCIENCE

The α v β 1 integrin plays a critical in vivo role in tissue fibrosis

(2015) Nilgun I. Reed et al.   Science Translational Medicine

Molecular Property Design: Does Everyone Get It?

(2015) Paul D. Leeson et al.   ACS Medicinal Chemistry Letters

Challenges for inhaled drug discovery and development: Induced alveolar macrophage responses

(2014) Ben Forbes et al.   ADVANCED DRUG DELIVERY REVIEWS

Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients withKRASwild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial

(2014) E. Élez et al.   ANNALS OF ONCOLOGY

RUC-4

(2014) Jihong Li et al.   ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY

A first-in-human study of the anti-α5β1 integrin monoclonal antibody PF-04605412 administered intravenously to patients with advanced solid tumors

(2014) J. Mateo et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Integrins αvβ5 and αvβ3 promote latent TGF-β1 activation by human cardiac fibroblast contraction

(2014) Vincent Sarrazy et al.   CARDIOVASCULAR RESEARCH

Strategies To Inhibit Tumor Associated Integrin Receptors: Rationale for Dual and Multi-Antagonists

(2014) Helen M. Sheldrake et al.   JOURNAL OF MEDICINAL CHEMISTRY

Therapeutic Targeting of Integrin αvβ6 in Breast Cancer

(2014) Kate M. Moore et al.   JNCI-Journal of the National Cancer Institute

Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial

(2014) Roger Stupp et al.   LANCET ONCOLOGY

Determining the optimal dose in the development of anticancer agents

(2014) Ron H. J. Mathijssen et al.   Nature Reviews Clinical Oncology

Structural determinants of integrin β-subunit specificity for latent TGF-β

(2014) Xianchi Dong et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Structural basis for pure antagonism of integrin αVβ3 by a high-affinity form of fibronectin

(2014) Johannes F Van Agthoven et al.   NATURE STRUCTURAL & MOLECULAR BIOLOGY

Selective Targeting of TGF-  Activation to Treat Fibroinflammatory Airway Disease

(2014) S. Minagawa et al.   Science Translational Medicine

Structure Activity Relationships of αv Integrin Antagonists for Pulmonary Fibrosis by Variation in Aryl Substituents

(2014) James Adams et al.   ACS Medicinal Chemistry Letters

Integrin modulators: a patent review

(2013) Tobias G Kapp et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

Safety, tolerability, and pharmacokinetics of the novel αv-integrin antibody EMD 525797 (DI17E6) in healthy subjects after ascending single intravenous doses

(2013) Wolfgang Uhl et al.   INVESTIGATIONAL NEW DRUGS

Preclinical SPECT/CT Imaging of  v 6 Integrins for Molecular Stratification of Idiopathic Pulmonary Fibrosis

(2013) A. E. John et al.   JOURNAL OF NUCLEAR MEDICINE

Plasma protein binding: From discovery to development

(2013) Tonika Bohnert et al.   JOURNAL OF PHARMACEUTICAL SCIENCES

Target validation using chemical probes

(2013) Mark E Bunnage et al.   Nature Chemical Biology

Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs

(2013) Neil C Henderson et al.   NATURE MEDICINE

Profile of the GSK Published Protein Kinase Inhibitor Set Across ATP-Dependent and-Independent Luciferases: Implications for Reporter-Gene Assays

(2013) Patricia Dranchak et al.   PLoS One

 v Integrins in Angiogenesis and Cancer

(2013) S. M. Weis et al.   Cold Spring Harbor Perspectives in Medicine

Tumor Targeting via Integrin Ligands

(2013) Udaya Kiran Marelli et al.   Frontiers in Oncology

A randomized, double-blind, multicenter, phase 2 study of a human monoclonal antibody to human αν integrins (intetumumab) in combination with docetaxel and prednisone for the first-line treatment of patients with metastatic castration-resistant prostate cancer

(2012) A. Heidenreich et al.   ANNALS OF ONCOLOGY

Phase Ib safety and pharmacokinetic study of volociximab, an anti-α5β1 integrin antibody, in combination with carboplatin and paclitaxel in advanced non-small-cell lung cancer

(2012) B. Besse et al.   ANNALS OF ONCOLOGY

Optimisation of DMPK by the Inhaled Route: Challenges and Approaches

(2012) Anne E. Cooper et al.   CURRENT DRUG METABOLISM

A human monoclonal antibody 264RAD targeting αvβ6 integrin reduces tumour growth and metastasis and modulates key biomarkers in vivo

(2012) C Eberlein et al.   ONCOGENE

Structure-Guided Design of a High-Affinity Platelet Integrin  IIb 3 Receptor Antagonist That Disrupts Mg2+ Binding to the MIDAS

(2012) J. Zhu et al.   Science Translational Medicine

In vitro investigation of integrin-receptor antagonist-induced vascular toxicity in the mouse

(2012) Deidre A. Dalmas Wilk et al.   TOXICOLOGY IN VITRO

Integrins as therapeutic targets

(2012) Simon L. Goodman et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Absence of Integrin αvβ3 Enhances Vascular Leak in Mice by Inhibiting Endothelial Cortical Actin Formation

(2011) George Su et al.   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

Introducing Lasso Peptides as Molecular Scaffolds for Drug Design: Engineering of an Integrin Antagonist

(2011) Thomas A. Knappe et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Cilengitide: The First Anti-Angiogenic Small Molecule Drug Candidate. Design, Synthesis and Clinical Evaluation

(2011) Carlos Mas-Moruno et al.   Anti-Cancer Agents in Medicinal Chemistry

A randomised, phase II study of intetumumab, an anti-αv-integrin mAb, alone and with dacarbazine in stage IV melanoma

(2011) S O'Day et al.   BRITISH JOURNAL OF CANCER

The role of β3-integrins in tumor angiogenesis: context is everything

(2011) Stephen D Robinson et al.   CURRENT OPINION IN CELL BIOLOGY

Getting physical in drug discovery II: the impact of chromatographic hydrophobicity measurements and aromaticity

(2011) Robert J. Young et al.   DRUG DISCOVERY TODAY

What makes a good drug target?

(2011) Isabella Gashaw et al.   DRUG DISCOVERY TODAY

Clinical and pharmacologic evaluation of two dose levels of intetumumab (CNTO 95) in patients with melanoma or angiosarcoma

(2011) Steven J. O’Day et al.   INVESTIGATIONAL NEW DRUGS

Tailoring of Integrin Ligands: Probing the Charge Capability of the Metal Ion-Dependent Adhesion Site

(2011) Markus Bollinger et al.   JOURNAL OF MEDICINAL CHEMISTRY

Health-related quality of life among patients with metastatic melanoma

(2011) Donald W. Robinson et al.   MELANOMA RESEARCH

Believe it or not: how much can we rely on published data on potential drug targets?

(2011) Florian Prinz et al.   NATURE REVIEWS DRUG DISCOVERY

Prodrugs--from Serendipity to Rational Design

(2011) K. M. Huttunen et al.   PHARMACOLOGICAL REVIEWS

Bleomycin revisited: towards a more representative model of IPF?

(2010) Chris J. Scotton et al.   AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY

Evaluation of the safety, pharmacokinetics and treatment effects of an ανβ3integrin inhibitor on bone turnover and disease activity in men with hormone-refractory prostate cancer and bone metastases

(2010) Mark A ROSENTHAL et al.   Asia-Pacific Journal of Clinical Oncology

A randomized phase 2 study of etaracizumab, a monoclonal antibody against integrin αvβ3, ± dacarbazine in patients with stage IV metastatic melanoma

(2010) Peter Hersey et al.   CANCER

Dual Functional Monoclonal Antibody PF-04605412 Targets Integrin  5 1 and Elicits Potent Antibody-Dependent Cellular Cytotoxicity

(2010) G. Li et al.   CANCER RESEARCH

Probing the Probes: Fitness Factors For Small Molecule Tools

(2010) Paul Workman et al.   CHEMISTRY & BIOLOGY

Targeting αvβ3 Integrin: Design and Applications of Mono- and Multifunctional RGD-Based Peptides and Semipeptides

(2010) L. Auzzas et al.   CURRENT MEDICINAL CHEMISTRY

Small Molecule Antagonists of Integrin Receptors

(2010) A. Perdih et al.   CURRENT MEDICINAL CHEMISTRY

Integrin–TGF-β crosstalk in fibrosis, cancer and wound healing

(2010) Coert Margadant et al.   EMBO REPORTS

A phase 1, multicenter, open-label study of the safety of two dose levels of a human monoclonal antibody to human αv integrins, intetumumab, in combination with docetaxel and prednisone in patients with castrate-resistant metastatic prostate cancer

(2010) Franklin M. Chu et al.   INVESTIGATIONAL NEW DRUGS

The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery

(2010) Dennis A. Smith et al.   NATURE REVIEWS DRUG DISCOVERY

Integrins as therapeutic targets: lessons and opportunities

(2010) Dermot Cox et al.   NATURE REVIEWS DRUG DISCOVERY

Breaking the Dogma of the Metal-Coordinating Carboxylate Group in Integrin Ligands: Introducing Hydroxamic Acids to the MIDAS To Tune Potency and Selectivity

(2009) Dominik Heckmann et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Preclinical Evaluation of the Novel Small-Molecule Integrin α5β1 Inhibitor JSM6427 in Monkey and Rabbit Models of Choroidal Neovascularization

(2009) Grit Zahn   ARCHIVES OF OPHTHALMOLOGY

Agonizing Integrin Antagonists?

(2009) Sara M. Weis et al.   CANCER CELL

Mechanism-based receptor-binding model to describe the pharmacokinetic and pharmacodynamic of an anti-α5β1 integrin monoclonal antibody (volociximab) in cancer patients

(2009) Chee M. Ng et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Genetic and cell biological analysis of integrin outside-in signaling

(2009) K. R. Legate et al.   GENES & DEVELOPMENT

Analysis of the Calculated Physicochemical Properties of Respiratory Drugs: Can We Design for Inhaled Drugs Yet?

(2009) Timothy J. Ritchie et al.   Journal of Chemical Information and Modeling

Small Molecule Integrin Antagonists in Cancer Therapy

(2009) Mayra Paolillo et al.   MINI-REVIEWS IN MEDICINAL CHEMISTRY

Will integrin inhibitors have proangiogenic effects in the clinic?

(2009) Michael Weller et al.   NATURE MEDICINE

Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors

(2009) Andrew R Reynolds et al.   NATURE MEDICINE

Physiochemical drug properties associated with in vivo toxicological outcomes

(2008) Jason D. Hughes et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

CYR61 and  V 5 Integrin Cooperate to Promote Invasion and Metastasis of Tumors Growing in Preirradiated Stroma

(2008) Y. Monnier et al.   CANCER RESEARCH

Pharmacology of the Novel Antiangiogenic Peptide ATN-161 (Ac-PHSCN-NH2): Observation of a U-Shaped Dose-Response Curve in Several Preclinical Models of Angiogenesis and Tumor Growth

(2008) F. Donate et al.   CLINICAL CANCER RESEARCH

Volociximab, a Chimeric Monoclonal Antibody that Specifically Binds  5 1 Integrin: A Phase I, Pharmacokinetic, and Biological Correlative Study

(2008) A. D. Ricart et al.   CLINICAL CANCER RESEARCH

Suzuki−Miyaura Approach to JNJ-26076713, an Orally Active Tetrahydroquinoline-Containing αVβ3/αVβ5Integrin Antagonist. Enantioselective Synthesis and Stereochemical Studies

(2008) William A. Kinney et al.   JOURNAL OF ORGANIC CHEMISTRY

Partial Inhibition of Integrin αvβ6 Prevents Pulmonary Fibrosis without Exacerbating Inflammation

(2007) Gerald S. Horan et al.   AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE