Imperial College London

ProfessorSaraRankin

Faculty of MedicineNational Heart & Lung Institute

Professor of Leukocyte and Stem Cell Biology
 
 
 
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Contact

 

+44 (0)20 7594 3172s.rankin

 
 
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Assistant

 

Ms Georgina Moss +44 (0)20 7594 2151

 
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Location

 

Office no. 351Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Jørgensen:2021:10.1038/s42003-021-02070-9,
author = {Jørgensen, AS and Daugvilaite, V and De, Filippo K and Berg, C and Mavri, M and Benned-Jensen, T and Juzenaite, G and Hjortø, G and Rankin, S and Våbenø, J and Rosenkilde, MM},
doi = {10.1038/s42003-021-02070-9},
journal = {Communications Biology},
pages = {569--569},
title = {Biased action of the CXCR4-targeting drug plerixafor is essential for its superior hematopoietic stem cell mobilization.},
url = {http://dx.doi.org/10.1038/s42003-021-02070-9},
volume = {4},
year = {2021}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Following the FDA-approval of the hematopoietic stem cell (HSC) mobilizer plerixafor, orally available and potent CXCR4 antagonists were pursued. One such proposition was AMD11070, which was orally active and had superior antagonism in vitro; however, it did not appear as effective for HSC mobilization in vivo. Here we show that while AMD11070 acts as a full antagonist, plerixafor acts biased by stimulating β-arrestin recruitment while fully antagonizing G protein. Consequently, while AMD11070 prevents the constitutive receptor internalization, plerixafor allows it and thereby decreases receptor expression. These findings are confirmed by the successful transfer of both ligands' binding sites and action to the related CXCR3 receptor. In vivo, plerixafor exhibits superior HSC mobilization associated with a dramatic reversal of the CXCL12 gradient across the bone marrow endothelium, which is not seen for AMD11070. We propose that the biased action of plerixafor is central for its superior therapeutic effect in HSC mobilization.
AU - Jørgensen,AS
AU - Daugvilaite,V
AU - De,Filippo K
AU - Berg,C
AU - Mavri,M
AU - Benned-Jensen,T
AU - Juzenaite,G
AU - Hjortø,G
AU - Rankin,S
AU - Våbenø,J
AU - Rosenkilde,MM
DO - 10.1038/s42003-021-02070-9
EP - 569
PY - 2021///
SN - 2399-3642
SP - 569
TI - Biased action of the CXCR4-targeting drug plerixafor is essential for its superior hematopoietic stem cell mobilization.
T2 - Communications Biology
UR - http://dx.doi.org/10.1038/s42003-021-02070-9
UR - https://www.ncbi.nlm.nih.gov/pubmed/33980979
UR - https://www.nature.com/articles/s42003-021-02070-9
UR - http://hdl.handle.net/10044/1/88841
VL - 4
ER -