Evidence map›Paper›PMID 23703610›Full record

ArticleThe Journal of biological chemistry2013

Small molecule agonist of very late antigen-4 (VLA-4) integrin induces progenitor cell adhesion.

Peter Vanderslice, Ronald J Biediger, Darren G Woodside, Wells S Brown, Sayadeth Khounlo, Navin D Warier, C William Gundlach, Amy R Caivano, William G Bornmann, David S Maxwell and 3 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.2field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Design and Pharmacological Characterization of αJournal of medicinal chemistry · 2023
    Article
  7. Poly(l-lactic acid) Scaffold Releasing an αACS applied bio materials · 2023
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Novel Ligands Targeting αFrontiers in chemistry · 2019
    Review
  16. Article
  17. Overexpression of VLA-4 in glial-restricted precursors enhances their endothelial docking and induces diapedesis in a mouse stroke model.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018
    Article
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 1 country.

Peter VandersliceDepartment of Molecular Cardiology, Texas Heart Institute at St. Luke's Episcopal Hospital, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Ronald J Biediger
Darren G Woodside
Wells S Brown
Sayadeth Khounlo
Navin D Warier
C William Gundlach
Amy R Caivano
William G Bornmann
David S Maxwell
Bradley W McIntyre
James T Willerson
Richard A F Dixon
St. Luke's Episcopal Hospital · USThe University of Texas MD Anderson Cancer Center · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Kathrin Milbury · 1985 to 2026
$290.8M
Training Program in Cancer ImmunobiologyT32CA009598 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ALLISON, JAMES P · 1988 to 2014
$4.9M
NCI NIH HHS 2 T32-CA-09598-21NCI NIH HHS CA016672NCI NIH HHS P30 CA016672NCI NIH HHS T32 CA009598
6 · The paper itself

Abstract

Activation of the integrin family of cell adhesion receptors on progenitor cells may be a viable approach to enhance the effects of stem cell-based therapies by improving cell retention and engraftment. Here, we describe the synthesis and characterization of the first small molecule agonist identified for the integrin α4β1 (also known as very late antigen-4 or VLA-4). The agonist, THI0019, was generated via two structural modifications to a previously identified α4β1 antagonist. THI0019 greatly enhanced the adhesion of cultured cell lines and primary progenitor cells to α4β1 ligands VCAM-1 and CS1 under both static and flow conditions. Furthermore, THI0019 facilitated the rolling and spreading of cells on VCAM-1 and the migration of cells toward SDF-1α. Molecular modeling predicted that the compound binds at the α/β subunit interface overlapping the ligand-binding site thus indicating that the compound must be displaced upon ligand binding. In support of this model, an analog of THI0019 modified to contain a photoreactive group was used to demonstrate that when cross-linked to the integrin, the compound behaves as an antagonist instead of an agonist. In addition, THI0019 showed cross-reactivity with the related integrin α4β7 as well as α5β1 and αLβ2. When cross-linked to αLβ2, the photoreactive analog of THI0019 remained an agonist, consistent with it binding at the α/β subunit interface and not at the ligand-binding site in the inserted ("I") domain of the αL subunit. Co-administering progenitor cells with a compound such as THI0019 may provide a mechanism for enhancing stem cell therapy.

Indexed as

Models, MolecularCD11a AntigenCell AdhesionCell- and Tissue-Based TherapyCell MovementChemokine CXCL12Heterocyclic Compounds, 4 or More RingsHumansHuman Umbilical Vein Endothelial CellsIntegrin alpha4beta1Integrin alpha5beta1Jurkat CellsStem CellsVascular Cell Adhesion Molecule-1CD11a AntigenChemokine CXCL12CXCL12 protein, humanHeterocyclic Compounds, 4 or More RingsIntegrin alpha4beta1Integrin alpha5beta1Vascular Cell Adhesion Molecule-1AgonistCell AdhesionCell TherapyFibronectinICAM-1IntegrinsProgenitor CellsStem CellsVCAM-1VLA-4

Identifiers

PMID23703610
PMCPMC3707645
OpenAlexW1989753828

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.