ArticleACS pharmacology & translational science2019
Novel Pure αVβ3 Integrin Antagonists That Do Not Induce Receptor Extension, Prime the Receptor, or Enhance Angiogenesis at Low Concentrations.
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Article in ACS pharmacology & translational science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25citing papers in PubMed
1.9field-weighted citation impact, top 15% of its field
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
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- Anoikis: To Die or Not to Die?International journal of molecular sciences · 2026Review
- Visualizing dynamics of membrane rafts on live cells.Science advances · 2025Article
- Therapeutic Use of Integrin Signaling in Melanoma Cells: Physical Link with the Extracellular Matrix (ECM).Cancers · 2025Review
- Focal adhesion in the tumour metastasis: from molecular mechanisms to therapeutic targets.Biomarker research · 2025Review
- Switching Roles─Exploring Concentration-Dependent Agonistic versus Antagonistic Behavior of Integrin Ligands.Journal of medicinal chemistry · 2025Article
- The Integrin Receptors: From Discovery to Structure to Medicines.Immunological reviews · 2025Review
- Structural insights into the molecular recognition of integrin αVβ3 by RGD-containing ligands: The role of the specificity-determining loop (SDL).bioRxiv : the preprint server for biology · 2024Article
- First-in-Class Humanized Antibody against Alternatively Spliced Tissue Factor Augments Anti-Metastatic Efficacy of Chemotherapy in a Preclinical Model of Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2024Article
- Conjecturing about Small-Molecule Agonists and Antagonists of α4β1 Integrin: From Mechanistic Insight to Potential Therapeutic Applications.Biomedicines · 2024Review
- Small Molecules against Metastatic Tumors: Concrete Perspectives and Shattered Dreams.Cancers · 2023Review
- Integrin αvβ3 Is a Master Regulator of Resistance to TKI-Induced Ferroptosis in HER2-Positive Breast Cancer.Cancers · 2023Article
- Discovery of C19-9 as a novel non-RGD inhibitor of αvβ3 to overcome enzalutamide resistance in castration-resistant prostate cancer.Signal transduction and targeted therapy · 2023Article
- Targeting integrin pathways: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2023Review
- INTEGRINS: A BEDSIDE TO BENCH TO BEDSIDE STORY.Transactions of the American Clinical and Climatological Association · 2023Article
- Structure-Based Discovery of a Novel Class of Small-Molecule Pure Antagonists of Integrin αVβ3.Journal of chemical information and modeling · 2022Article
- Article
- Molecular ZIP codes in targeted drug delivery.Proceedings of the National Academy of Sciences of the United States of America · 2022Review
- First-in-Human Study of [Diagnostics (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
28 authors at 9 institutions in 3 countries.
Jihong LiAllen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
Yoshiyuki FukaseTri-Institutional Therapeutics Discovery Institute, 413 East 69 Street, New York, New York 10021, United States.
Yi ShangDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1677, New York, New York 10029-6574, United States.
Wei ZouWashington University School of Medicine, Campus Box 8118, 660 South Euclid Avenue, St. Louis, Missouri 63110, United States.
José M Muñoz-FélixAdhesion and Angiogenesis Laboratory, Centre for Tumour Biology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, United Kingdom.
Lorena BuitragoAllen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
Johannes van AgthovenLeukocyte Biology and Inflammation and Structural Biology Programs, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, United States.
Yixiao ZhangLaboratory of Molecular Electron Microscopy, Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
Ryoma HaraTri-Institutional Therapeutics Discovery Institute, 413 East 69 Street, New York, New York 10021, United States.
Yuta TanakaTri-Institutional Therapeutics Discovery Institute, 413 East 69 Street, New York, New York 10021, United States.
Rei OkamotoTri-Institutional Therapeutics Discovery Institute, 413 East 69 Street, New York, New York 10021, United States.
Takeshi YasuiTri-Institutional Therapeutics Discovery Institute, 413 East 69 Street, New York, New York 10021, United States.
Takashi NakahataTri-Institutional Therapeutics Discovery Institute, 413 East 69 Street, New York, New York 10021, United States.
Toshihiro ImaedaTri-Institutional Therapeutics Discovery Institute, 413 East 69 Street, New York, New York 10021, United States.
Kazuyoshi AsoTri-Institutional Therapeutics Discovery Institute, 413 East 69 Street, New York, New York 10021, United States.
Yuchen ZhouDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1677, New York, New York 10029-6574, United States.
Charles LocusonAgios Pharmaceuticals, 88 Sidney Street, Cambridge, Massachusetts 02139-4169, United States.
Dragana NesicAllen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
Mark DugganLifeSci Consulting, LLC, 18243 SE Ridgeview Drive, Tequesta, Florida 33469, United States.
Junichi TakagiLaboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Roger D VaughanRockefeller University Center for Clinical and Translational Science, Rockefeller University, 2130 York Avenue, New York, New York 10065, United States.
Thomas WalzLaboratory of Molecular Electron Microscopy, Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
Kairbaan Hodivala-DilkeAdhesion and Angiogenesis Laboratory, Centre for Tumour Biology, Barts Cancer Institute-a CR-UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London, EC1M 6BQ, United Kingdom.
Steven L TeitelbaumWashington University School of Medicine, Campus Box 8118, 660 South Euclid Avenue, St. Louis, Missouri 63110, United States.
M Amin ArnaoutLeukocyte Biology and Inflammation and Structural Biology Programs, Division of Nephrology, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, United States.
Marta FilizolaDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1677, New York, New York 10029-6574, United States.
Michael A FoleyTri-Institutional Therapeutics Discovery Institute, 413 East 69 Street, New York, New York 10021, United States.
Barry S CollerAllen and Frances Adler Laboratory of Blood and Vascular Biology, Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
Tri-Institutional Therapeutics Discovery Institute · USRockefeller University · USIcahn School of Medicine at Mount Sinai · USHarvard University · USQueen Mary University of London · GBWashington University in St. Louis · USAgios Pharmaceuticals (United States) · USProtein Research Foundation · JPRidgeview · US
Funding
Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational SuccessUL1TR001866 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY, KRUEGER, JAMES G · 2016 to 2025
$40.6MPlatelet Integrin AlphaIIbBeta3 Structure, Activation, and Ligand Binding: Fibrinogen, Fibrin, D-dimer, and von Willebrand FactorR01HL019278 · NHLBI · STATE UNIVERSITY NEW YORK STONY BROOK · PI Claudia Lorena Buitrago, Barry Coller · 1985 to 2026
$17.6MResource Based Center for Musculoskeletal Biology and Medicine (Overall Application)P30AR074992 · NIAMS · WASHINGTON UNIVERSITY · PI MATTHEW J SILVA · 2019 to 2026
$6.8MStructure and Function of beta2 IntegrinR01DK048549 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI ARNAOUT, M. AMIN · 1994 to 2016
$6.0MThe Role of the Osteoblast Secretome in Bone FormationP30AR057235 · NIAMS · WASHINGTON UNIVERSITY · PI SILVA, MATTHEW J · 2009 to 2018
$5.7MStructure and Function of Integrins in the KidneyR01DK088327 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI ARNAOUT, M. AMIN · 2010 to 2025
$5.3MMECHANISMS OF AVB3 INTEGRIN MEDIATED BONE RESORPTIONR01AR046523 · NIAMS · WASHINGTON UNIVERSITY · PI TEITELBAUM, STEVEN L · 2000 to 2009
$4.0MPlatelet alphaIIbbeta3 activation and its therapeutic targetingR01HL141366 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BRIAN D ADAIR, M. AMIN ARNAOUT · 2019 to 2026
$3.6MMechanisms of AVB3 Integrin Mediated Bone ResorptionR37AR046523 · NIAMS · WASHINGTON UNIVERSITY · PI TEITELBAUM, STEVEN L · 2010 to 2019
$3.3MTransforming Genomics with 5 PB Big Omics Data Engine Cray CS300-AC SupercomputerS10OD018522 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2014 to 2014
$1.9MFAT TALKS TO BONER01DK111389 · NIDDK · WASHINGTON UNIVERSITY · PI TEITELBAUM, STEVEN L · 2017 to 2021
$1.9MNovel Features of Integrin Antagonism Applied to Renal DysfunctionK01DK101628 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI VAN AGTHOVEN, JOHANNES FRANCISCUS · 2015 to 2019
$797kNCATS NIH HHS UL1 TR001866NHLBI NIH HHS R01 HL019278NHLBI NIH HHS R01 HL141366NIAMS NIH HHS P30 AR057235NIAMS NIH HHS P30 AR074992NIAMS NIH HHS R01 AR046523NIAMS NIH HHS R37 AR046523NIDDK NIH HHS K01 DK101628NIDDK NIH HHS R01 DK048549NIDDK NIH HHS R01 DK088327NIDDK NIH HHS R01 DK111389NIH HHS S10 OD018522Worldwide Cancer Research 16-0390
Abstract
The integrin αVβ3 receptor has been implicated in several important diseases, but no antagonists are approved for human therapy. One possible limitation of current small-molecule antagonists is their ability to induce a major conformational change in the receptor that induces it to adopt a high-affinity ligand-binding state. In response, we used structural inferences from a pure peptide antagonist to design the small-molecule pure antagonists TDI-4161 and TDI-3761. Both compounds inhibit αVβ3-mediated cell adhesion to αVβ3 ligands, but do not induce the conformational change as judged by antibody binding, electron microscopy, X-ray crystallography, and receptor priming studies. Both compounds demonstrated the favorable property of inhibiting bone resorption
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