Evidence map›Paper›PMID 33705358›Full record

ArticleJCI insight2021

Saracatinib is an efficacious clinical candidate for fibrodysplasia ossificans progressiva.

Eleanor Williams, Jana Bagarova, Georgina Kerr, Dong-Dong Xia, Elsie S Place, Devaveena Dey, Yue Shen, Geoffrey A Bocobo, Agustin H Mohedas, Xiuli Huang and 7 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed
9.2field-weighted citation impact, top 1% 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

51 citing papers in PubMed, 68 citations in OpenAlex.

  1. Trial
  2. Article
  3. Integrative Transcriptomic Profiling Delineates LTBP4-Driven Fibroblast Reprogramming Across the Ossification Continuum of the Ligamentum Flavum.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Fyn-Saracatinib Complex Structure Reveals an Active State-like Conformation.International journal of molecular sciences · 2026
    Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
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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

17 authors at 5 institutions in 2 countries.

Eleanor WilliamsCentre for Medicines Discovery, University of Oxford, Oxford, United Kingdom.
Jana BagarovaDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Georgina KerrCentre for Medicines Discovery, University of Oxford, Oxford, United Kingdom.
Dong-Dong XiaDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Elsie S PlaceDevelopmental Biology Laboratory, Francis Crick Institute, London, United Kingdom.
Devaveena DeyDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Yue ShenDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Geoffrey A BocoboDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Agustin H MohedasDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Xiuli HuangNational Center for Advancing Translational Sciences, NIH, Bethesda, Maryland, USA.
Philip E SandersonNational Center for Advancing Translational Sciences, NIH, Bethesda, Maryland, USA.
Arthur LeeNational Center for Advancing Translational Sciences, NIH, Bethesda, Maryland, USA.
Wei ZhengNational Center for Advancing Translational Sciences, NIH, Bethesda, Maryland, USA.
Aris N EconomidesRegeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
James C SmithDevelopmental Biology Laboratory, Francis Crick Institute, London, United Kingdom.
Paul B YuDepartment of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Alex N BullockCentre for Medicines Discovery, University of Oxford, Oxford, United Kingdom.
Brigham and Women's Hospital · USNational Center for Advancing Translational Sciences · USUniversity of Oxford · GBThe Francis Crick Institute · GBRegeneron (United States) · US

Funding

Drug Repurposing Screening for Rare and Neglected DiseasesZIATR000018 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI ZHENG, WEI · 2015 to 2025
$24.6M
TRAINING PROGRAM IN CARDIOVASCULAR RESEARCHT32HL007604 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI MARK W FEINBERG · 1985 to 2026
$19.0M
BMP Inhibitors to Treat Fibrodysplasia Ossificans ProgressivaZIATR000008 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI SANDERSON, PHILIP · 2015 to 2021
$10.7M
Novel probes of BMP and TGF-beta signaling and functionR01AR057374 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI YU, PAUL B · 2010 to 2023
$4.5M
Repositioning AZD0530 for surgical treatment of fibrodysplasia ossificans progressivaUG3TR002617 · NCATS · BRIGHAM AND WOMEN'S HOSPITAL · PI YU, PAUL B · 2018 to 2019
$702k
NCATS NIH HHS UG3 TR002617NHLBI NIH HHS T32 HL007604NIAMS NIH HHS R01 AR057374Wellcome Trust FC001157
6 · The paper itself

Abstract

Currently, no effective therapies exist for fibrodysplasia ossificans progressiva (FOP), a rare congenital syndrome in which heterotopic bone is formed in soft tissues owing to dysregulated activity of the bone morphogenetic protein (BMP) receptor kinase ALK2 (also known as ACVR1). From a screen of known biologically active compounds, we identified saracatinib as a potent ALK2 kinase inhibitor. In enzymatic and cell-based assays, saracatinib preferentially inhibited ALK2, compared with other receptors of the BMP/TGF-β signaling pathway, and induced dorsalization in zebrafish embryos consistent with BMP antagonism. We further tested the efficacy of saracatinib using an inducible ACVR1Q207D-transgenic mouse line, which provides a model of heterotopic ossification (HO), as well as an inducible ACVR1R206H-knockin mouse, which serves as a genetically and physiologically faithful FOP model. In both models, saracatinib was well tolerated and potently inhibited the development of HO, even when administered transiently following soft tissue injury. Together, these data suggest that saracatinib is an efficacious clinical candidate for repositioning in FOP treatment, offering an accelerated path to clinical proof-of-efficacy studies and potentially significant benefits to individuals with this devastating condition.

Indexed as

Activin Receptors, Type IAnimalsBenzodioxolesBone Morphogenetic ProteinsDrug Evaluation, PreclinicalGene Knock-In TechniquesMiceMice, TransgenicMusclesMyositis OssificansOssification, HeterotopicQuinazolinesZebrafishActivin Receptors, Type IAcvr1 protein, mouseBenzodioxolesBone Morphogenetic ProteinsQuinazolinessaracatinibBone BiologyDrug screensGrowth factorsProtein kinasesTherapeutics

Identifiers

PMID33705358
PMCPMC8119212
OpenAlexW3134020977

What OpenQuestion holds

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LicenceCC BY
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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.