ArticleNature communications2022
Identification of a binding site on soluble RANKL that can be targeted to inhibit soluble RANK-RANKL interactions and treat osteoporosis.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 66 citations in OpenAlex.
- Osteoprotegerin and receptor activator of NF-kappaB ligand as biomarkers for bone resorption-related disorders.World journal of experimental medicine · 2026Review
- Sulfated polysaccharides target RANK Lys97 to inhibit osteoclast differentiation and reverse osteoporosis.Nature biomedical engineering · 2026Article
- Molecular-level understanding of the aging bone and regeneration mechanisms using computational methods.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Review
- Strontium-Containing Bioactive Glass Nanoparticles Stimulate Osteogenesis and Suppress Osteoclast Formation in Co-Culture.Advanced healthcare materials · 2026Article
- Progress on novel compounds for the treatment of bone metabolism-related disorders: focus on osteoporosis and beyond.Frontiers in chemistry · 2026Review
- Managing Rebound Bone Loss After Denosumab Discontinuation: Mechanisms, Risk Stratification, and Sequential Therapy.Drug design, development and therapy · 2026Review
- Revolutionizing osteoporosis management: the emerging role of immunotherapeutic and next-generation therapies.Inflammopharmacology · 2025Review
- Generation and Purification of RANKL-Derived Small-Fragment Variants for Osteoclast Inhibition.Pharmaceutics · 2025Article
- Review
- The p53-miR17 family-Rankl axis bridges liver-bone communication.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- C-X-C motif chemokine ligand 13 suppresses osteoclast differentiation via interference with RANKL-RANK interaction.Frontiers in immunology · 2025Article
- Global knowledge mapping of receptor activator of nuclear factor kappa-B ligand in osteoporotic fractures: a bibliometric analysis (2001-2024).Frontiers in molecular biosciences · 2025Review
- Pan-histone deacetylase inhibitor vorinostat suppresses osteoclastic bone resorption through modulation of RANKL-evoked signaling and ameliorates ovariectomy-induced bone loss.Cell communication and signaling : CCS · 2024Article
- Computational design of anti-cancer peptides tailored to target specific tumor markers.BMC chemistry · 2024Article
- Yunnan Baiyao Might Mitigate Periodontitis Bone Destruction by Inhibiting Autophagy and Promoting Osteoblast Differentiation in vivo, ex vivo and in vitro.Journal of inflammation research · 2024Article
- Benzophenones-natural metabolites with great Hopes in drug discovery: structures, occurrence, bioactivities, and biosynthesis.RSC advances · 2023Review
- Review
- Targeting strategies for bone diseases: signaling pathways and clinical studies.Signal transduction and targeted therapy · 2023Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One of the major challenges for discovering protein-protein interaction inhibitors is identifying selective and druggable binding sites at the protein surface. Here, we report an approach to identify a small molecular binding site to selectively inhibit the interaction of soluble RANKL and RANK for designing anti-osteoporosis drugs without undesirable immunosuppressive effects. Through molecular dynamic simulations, we discovered a binding site that allows a small molecule to selectively interrupt soluble RANKL-RANK interaction and without interfering with the membrane RANKL-RANK interaction. We describe a highly potent inhibitor, S3-15, and demonstrate its specificity to inhibit the soluble RANKL-RANK interaction with in vitro and in vivo studies. S3-15 exhibits anti-osteoporotic effects without causing immunosuppression. Through in silico and in vitro experiments we further confirm the binding model of S3-15 and soluble RANKL. This work might inspire structure-based drug discovery for targeting protein-protein interactions.
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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.