Nature Communications (Nov 2021)
The chemotherapeutic CX-5461 primarily targets TOP2B and exhibits selective activity in high-risk neuroblastoma
- Min Pan,
- William C. Wright,
- Richard H. Chapple,
- Asif Zubair,
- Manbir Sandhu,
- Jake E. Batchelder,
- Brandt C. Huddle,
- Jonathan Low,
- Kaley B. Blankenship,
- Yingzhe Wang,
- Brittney Gordon,
- Payton Archer,
- Samuel W. Brady,
- Sivaraman Natarajan,
- Matthew J. Posgai,
- John Schuetz,
- Darcie Miller,
- Ravi Kalathur,
- Siquan Chen,
- Jon Patrick Connelly,
- M. Madan Babu,
- Michael A. Dyer,
- Shondra M. Pruett-Miller,
- Burgess B. Freeman,
- Taosheng Chen,
- Lucy A. Godley,
- Scott C. Blanchard,
- Elizabeth Stewart,
- John Easton,
- Paul Geeleher
Affiliations
- Min Pan
- Department of Computational Biology, St. Jude Children’s Research Hospital
- William C. Wright
- Department of Computational Biology, St. Jude Children’s Research Hospital
- Richard H. Chapple
- Department of Computational Biology, St. Jude Children’s Research Hospital
- Asif Zubair
- Department of Computational Biology, St. Jude Children’s Research Hospital
- Manbir Sandhu
- Department of Structural Biology, St. Jude Children’s Research Hospital
- Jake E. Batchelder
- Department of Structural Biology, St. Jude Children’s Research Hospital
- Brandt C. Huddle
- The Department of Physiology and Biophysics, Weill Cornell Medicine
- Jonathan Low
- Department of Chemical Biology and Therapeutics, St. Jude Children’s Research Hospital
- Kaley B. Blankenship
- Department of Oncology, St. Jude Children’s Research Hospital
- Yingzhe Wang
- Preclinical Pharmacokinetic Shared Resource, St. Jude Children’s Research Hospital
- Brittney Gordon
- Department of Developmental Neurobiology, St. Jude Children’s Research Hospital
- Payton Archer
- Department of Oncology, St. Jude Children’s Research Hospital
- Samuel W. Brady
- Department of Computational Biology, St. Jude Children’s Research Hospital
- Sivaraman Natarajan
- Department of Computational Biology, St. Jude Children’s Research Hospital
- Matthew J. Posgai
- Departments of Medicine and Human Genetics, The University of Chicago
- John Schuetz
- Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital
- Darcie Miller
- Department of Structural Biology, St. Jude Children’s Research Hospital
- Ravi Kalathur
- Department of Structural Biology, St. Jude Children’s Research Hospital
- Siquan Chen
- Cellular Screening Center, The University of Chicago
- Jon Patrick Connelly
- Department of Cell and Molecular Biology, St. Jude Children’s Research Hospital
- M. Madan Babu
- Department of Structural Biology, St. Jude Children’s Research Hospital
- Michael A. Dyer
- Department of Developmental Neurobiology, St. Jude Children’s Research Hospital
- Shondra M. Pruett-Miller
- Department of Cell and Molecular Biology, St. Jude Children’s Research Hospital
- Burgess B. Freeman
- Preclinical Pharmacokinetic Shared Resource, St. Jude Children’s Research Hospital
- Taosheng Chen
- Department of Chemical Biology and Therapeutics, St. Jude Children’s Research Hospital
- Lucy A. Godley
- Departments of Medicine and Human Genetics, The University of Chicago
- Scott C. Blanchard
- Department of Structural Biology, St. Jude Children’s Research Hospital
- Elizabeth Stewart
- Department of Oncology, St. Jude Children’s Research Hospital
- John Easton
- Department of Computational Biology, St. Jude Children’s Research Hospital
- Paul Geeleher
- Department of Computational Biology, St. Jude Children’s Research Hospital
- DOI
- https://doi.org/10.1038/s41467-021-26640-x
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 20
Abstract
CX-5461 recently progressed through phase I clinical trial as a first-inhuman inhibitor of RNA-POL I. Here, the authors demonstrate that CX-5461 synergizes with topoisomerase I inhibitors to inhibit neuroblastoma cells and that its primary target in this disease is topoisomerase II beta and not RNA-POL I.
