Literature DB >> 20885411

Integrins as therapeutic targets: lessons and opportunities.

Dermot Cox1, Marian Brennan, Niamh Moran.   

Abstract

The integrins are a large family of cell adhesion molecules that are essential for the regulation of cell growth and function. The identification of key roles for integrins in a diverse range of diseases, including cancer, infection, thrombosis and autoimmune disorders, has revealed their substantial potential as therapeutic targets. However, so far, pharmacological inhibitors for only three integrins have received marketing approval. This article discusses the structure and function of integrins, their roles in disease and the chequered history of the approved integrin antagonists. Recent advances in the understanding of integrin function, ligand interaction and signalling pathways suggest novel strategies for inhibiting integrin function that could help harness their full potential as therapeutic targets.

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Year:  2010        PMID: 20885411     DOI: 10.1038/nrd3266

Source DB:  PubMed          Journal:  Nat Rev Drug Discov        ISSN: 1474-1776            Impact factor:   84.694


  201 in total

1.  A structural basis for integrin activation by the cytoplasmic tail of the alpha IIb-subunit.

Authors:  O Vinogradova; T Haas; E F Plow; J Qin
Journal:  Proc Natl Acad Sci U S A       Date:  2000-02-15       Impact factor: 11.205

2.  Increased mortality with oral platelet glycoprotein IIb/IIIa antagonists: a meta-analysis of phase III multicenter randomized trials.

Authors:  D P Chew; D L Bhatt; S Sapp; E J Topol
Journal:  Circulation       Date:  2001-01-16       Impact factor: 29.690

Review 3.  Drug-induced immune thrombocytopenia.

Authors:  Richard H Aster; Daniel W Bougie
Journal:  N Engl J Med       Date:  2007-08-09       Impact factor: 91.245

Review 4.  The tail of integrins, talin, and kindlins.

Authors:  Markus Moser; Kyle R Legate; Roy Zent; Reinhard Fässler
Journal:  Science       Date:  2009-05-15       Impact factor: 47.728

5.  A small molecule that inhibits the interaction of paxillin and alpha 4 integrin inhibits accumulation of mononuclear leukocytes at a site of inflammation.

Authors:  Christiane Kummer; Brian G Petrich; David M Rose; Mark H Ginsberg
Journal:  J Biol Chem       Date:  2010-01-22       Impact factor: 5.157

6.  C-reactive protein binds to alphaIIbbeta3.

Authors:  M P Brennan; R D Moriarty; S Grennan; A J Chubb; D Cox
Journal:  J Thromb Haemost       Date:  2008-07-01       Impact factor: 5.824

7.  A deletion in the alpha subunit locks platelet integrin alpha IIb beta 3 into a high affinity state.

Authors:  K Peter; C Bode
Journal:  Blood Coagul Fibrinolysis       Date:  1996-03       Impact factor: 1.276

8.  The volatile anesthetic isoflurane perturbs conformational activation of integrin LFA-1 by binding to the allosteric regulatory cavity.

Authors:  Koichi Yuki; Nathan S Astrof; Clay Bracken; Ronnie Yoo; Whitney Silkworth; Sulpicio G Soriano; Motomu Shimaoka
Journal:  FASEB J       Date:  2008-08-15       Impact factor: 5.191

9.  Integrin-using rotaviruses bind alpha2beta1 integrin alpha2 I domain via VP4 DGE sequence and recognize alphaXbeta2 and alphaVbeta3 by using VP7 during cell entry.

Authors:  Kate L Graham; Peter Halasz; Yan Tan; Marilyn J Hewish; Yoshikazu Takada; Erich R Mackow; Martyn K Robinson; Barbara S Coulson
Journal:  J Virol       Date:  2003-09       Impact factor: 5.103

10.  Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study.

Authors:  Eva Havrdova; Steven Galetta; Michael Hutchinson; Dusan Stefoski; David Bates; Chris H Polman; Paul W O'Connor; Gavin Giovannoni; J Theodore Phillips; Fred D Lublin; Amy Pace; Richard Kim; Robert Hyde
Journal:  Lancet Neurol       Date:  2009-02-07       Impact factor: 44.182

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  171 in total

1.  Expression of αV-integrins in uterine serous papillary carcinomas; implications for targeted therapy with intetumumab (CNTO 95), a fully human antagonist anti-αV-integrin antibody.

Authors:  Marta Bellone; Emiliano Cocco; Joyce Varughese; Stefania Bellone; Paola Todeschini; Karim El-Sahwi; Luisa Carrara; Federica Guzzo; Peter E Schwartz; Thomas J Rutherford; Sergio Pecorelli; Deborah J Marshall; Alessandro D Santin
Journal:  Int J Gynecol Cancer       Date:  2011-08       Impact factor: 3.437

2.  Integrin activation as an alternative treatment approach for inflammatory diseases.

Authors:  Vincent Kam Wai Wong; Liang Liu
Journal:  Acta Pharmacol Sin       Date:  2011-10-31       Impact factor: 6.150

3.  Integrin antagonists prevent costimulatory blockade-resistant transplant rejection by CD8(+) memory T cells.

Authors:  W H Kitchens; D Haridas; M E Wagener; M Song; A D Kirk; C P Larsen; M L Ford
Journal:  Am J Transplant       Date:  2011-09-22       Impact factor: 8.086

4.  The C-terminal αI domain linker as a critical structural element in the conformational activation of αI integrins.

Authors:  Gabriele Weitz-Schmidt; Thomas Schürpf; Timothy A Springer
Journal:  J Biol Chem       Date:  2011-09-30       Impact factor: 5.157

Review 5.  Integrin α3β1 as a breast cancer target.

Authors:  Sita Subbaram; C Michael Dipersio
Journal:  Expert Opin Ther Targets       Date:  2011-08-13       Impact factor: 6.902

Review 6.  Understanding the bone marrow microenvironment in hematologic malignancies: A focus on chemokine, integrin, and extracellular vesicle signaling.

Authors:  Edward Allan Racela Sison; Peter Kurre; Yong-Mi Kim
Journal:  Pediatr Hematol Oncol       Date:  2017-12-06       Impact factor: 1.969

7.  The secreted protein DEL-1 activates a β3 integrin-FAK-ERK1/2-RUNX2 pathway and promotes osteogenic differentiation and bone regeneration.

Authors:  Da-Yo Yuh; Tomoki Maekawa; Xiaofei Li; Tetsuhiro Kajikawa; Khalil Bdeir; Triantafyllos Chavakis; George Hajishengallis
Journal:  J Biol Chem       Date:  2020-04-12       Impact factor: 5.157

8.  Effects of VLA-1 Blockade on Experimental Inflammation in Mice.

Authors:  Ryuichi Totsuka; Takaaki Kondo; Shigeki Matsubara; Midori Hirai; Yoichi Kurebayashi
Journal:  Kobe J Med Sci       Date:  2016-07-05

Review 9.  Redox-relevant aspects of the extracellular matrix and its cellular contacts via integrins.

Authors:  Johannes A Eble; Flávia Figueiredo de Rezende
Journal:  Antioxid Redox Signal       Date:  2014-01-08       Impact factor: 8.401

10.  Platelet integrin α6β1 controls lung metastasis through direct binding to cancer cell-derived ADAM9.

Authors:  Elmina Mammadova-Bach; Paola Zigrino; Camille Brucker; Catherine Bourdon; Monique Freund; Adèle De Arcangelis; Scott I Abrams; Gertaud Orend; Christian Gachet; Pierre Henri Mangin
Journal:  JCI Insight       Date:  2016-09-08
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