ReviewBone2018
Structural basis for the potent and selective binding of LDN-212854 to the BMP receptor kinase ALK2.
Review in Bone, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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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.
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.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Angiogenesis in ossification of the posterior longitudinal ligament: progress from mechanism to targeted intervention.Frontiers in cell and developmental biology · 2026Review
- Depletion of marrow adipo-CAR cells in mice enhances bone formation by activating bone morphogenetic protein receptor (BMPR) in pre-osteoblasts.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Article
- Discovery of highly potent and ALK2/ALK1 selective kinase inhibitors using DNA-encoded chemistry technology.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Emerging role of BMPs/BMPR2 signaling pathway in treatment for pulmonary fibrosis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Review
- TP-0184 inhibits FLT3/ACVR1 to overcome FLT3 inhibitor resistance and hinder AML growth synergistically with venetoclax.Leukemia · 2024Article
- Reduced GS Domain Serine/Threonine Requirements of Fibrodysplasia Ossificans Progressiva Mutant Type I BMP Receptor ACVR1 in the Zebrafish.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Article
- Review
- Suppression of heterotopic ossification in fibrodysplasia ossificans progressiva using AAV gene delivery.Nature communications · 2022Article
- Discovery of Novel Pyrazolopyrimidines as Potent, Selective, and Orally Bioavailable Inhibitors of ALK2.ACS medicinal chemistry letters · 2022Article
- Pathophysiology and Emerging Molecular Therapeutic Targets in Heterotopic Ossification.International journal of molecular sciences · 2022Review
- Graphene oxide-functionalized nanocomposites promote osteogenesis of human mesenchymal stem cells via enhancement of BMP-SMAD1/5 signaling pathway.Biomaterials · 2021Article
- Recent Advances in ALK2 Inhibitors.ACS omega · 2021Review
- Do Interactions of Vitamin DCurrent osteoporosis reports · 2021Review
- Ablation of Fat Cells in Adult Mice Induces Massive Bone Gain.Cell metabolism · 2020Article
- Review
- Article
- Prophylactic treatment of rapamycin ameliorates naturally developing and episode -induced heterotopic ossification in mice expressing human mutant ACVR1.Orphanet journal of rare diseases · 2020Article
- Structural biology of the TGFβ family.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- Targeting heterotopic ossification by inhibiting activin receptor‑like kinase 2 function (Review).Molecular medicine reports · 2019Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Individuals with the rare developmental disorder fibrodysplasia ossificans progressiva (FOP) experience disabling heterotopic ossification caused by a gain of function mutation in the intracellular region of the BMP type I receptor kinase ALK2, encoded by the gene ACVR1. Small molecule BMP type I receptor inhibitors that block this ossification in FOP mouse models have been derived from the pyrazolo[1,5-a]pyrimidine scaffold of dorsomorphin. While the first derivative LDN-193189 exhibited pan inhibition of BMP receptors, the more recent compound LDN-212854 has shown increased selectivity for ALK2. Here we solved the crystal structure of ALK2 in complex with LDN-212854 to define how its binding interactions compare to previously reported BMP and TGFβ receptor inhibitors. LDN-212854 bound to the kinase hinge region as a typical type I ATP-competitive inhibitor with a single hydrogen bond to ALK2 His286. Specificity arising from the 5-quinoline moiety was associated with a distinct pattern of water-mediated hydrogen bonds involving Lys235 and Glu248 in the inactive conformation favoured by ALK2. The structure of this complex provides a template for the design of future ALK2 inhibitors under development for the treatment of FOP and other related conditions of heterotopic ossification.
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Registered trials
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.