DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for bone remodeling disease — screening already-approved drugs against its 30-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBone remodeling disease maps to a 30-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
approvedMetforminApproved drugapprovedDasatinibApproved drugapprovedPazopanibApproved drug
Structures already discussed alongside bone remodeling disease in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of EphA4 kinase domain — Dasatinib has a real, experimentally solved structure in complex with this target (PDB 2Y6O, 1.543 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet 1n1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2Y6O · 1.543 Å · ligand Dasatinib (1N1). Experimental structure, not a prediction.
What the evidence adds up to
A 1982 review states that bone loss in osteoporosis appears permanent, and that treatment goals are to control progression and prevent complications, with intervention able to retard or sometimes halt the process if diagnosed early. A 2016 review notes that mapping bone remodelling signalling pathways has provided a scientific basis for developing pharmaceuticals that can induce or suppress bone formation, and that enhancing bone healing and establishing a predetermined skeletal phenotype are now considered within reach.
A 2025 review of craniofacial fibrous dysplasia, a rare disorder where bone is replaced by fibrous tissue, describes the condition as driven by GNAS gene mutations that cause dysregulation of multiple signalling pathways, involving molecules such as cAMP-response element binding protein, interleukin-6, and Fibroblast growth factor 23. It evaluates the limitations of traditional treatments and the translational potential of novel targeted therapies, but provides no clinical trial results or patient outcome data.
A 2022 prospective observational study of 50 patients with lateral fragility femur fractures treated by intramedullary nailing compared 25 patients given clodronic acid plus vitamin D against 25 given vitamin D alone. At 12 months, the group receiving clodronic acid showed a statistically significant increase in bone mineral density in one region of interest under the head screw (0.93±0.07 gr/cm² vs 0.88±0.08 gr/cm², p=0.04). Biochemical and densitometric values improved from baseline in the combination group, while the vitamin D-only group improved only biochemically. The study concludes that adequate drug therapy after surgery can lead to better control of bone remodelling and reabsorption.
What is still missing are large randomised controlled trials with fracture outcomes rather than surrogate markers, particularly for the combination of clodronic acid and vitamin D. For craniofacial fibrous dysplasia, no clinical trial data for targeted therapies exist. The 1982 and 2016 reviews do not provide patient-level evidence. Patient stratification by disease subtype, genetic mutation, or bone turnover status remains unexplored in these studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Bone and Mineral Research · 2010 · 89 citations
The tyrosine kinase inhibitor dasatinib dysregulates bone remodeling through inhibition of osteoclasts in vivo
AbstractDasatinib is a potent tyrosine kinase inhibitor that is used to treat chronic myeloid leukemia in patients resistant or intolerant to imatinib mesylate. While designed to inhibit Abl and Src kinases, dasatinib shows multitarget effects, including inhibition of the macrophage colony-stimulating factor (M-CSF) receptor c-fms. We have shown previously that dasatinib abrogates osteoclast formation and activity in vitro owing, in part, to its specificity for c-fms. In this study we examined whether dasatinib could significantly alter bone volume in a model of physiologic bone turnover. Sprague-Dawley rats were administered dasatinib (5 mg/kg/day) or vehicle by gavage or zoledronic acid (ZOL; 100 microg/kg/6 weeks) subcutaneously. Following 4, 8, and 12 weeks of treatment, serum biochemical, bone morphometric, and histologic analyses were performed. Whole-body bone mineral density and tibial cortical thickness where unchanged in the dasatinib- or ZOL-treated animals relative to controls. However, micro-computed tomographic (microCT) analysis of cancellous bone at the proximal tibias showed that trabecular volume (BV/TV) and thickness (Tb.Th) were increased in dasatinib-treated animals at levels comparable with those of the ZOL-treated group. These changes were associated with a decrease in osteoclast numbers (N.Oc/B.Pm) and surface (Oc.S/BS) and decreased serum levels of the osteoclast marker c-terminal collagen crosslinks (CTX-1). Mineral apposition rate (MAR), bone-formation rate (BFR), and levels of the serum osteoblast markers osteocalcin and N-terminal propeptide of type I procollagen (P1NP) were not altered significantly in the dasatinib-treated animals relative to controls. These studies show that dasatinib increases trabecular bone volume at least in part by inhibiting osteoclast activity, suggesting that dasatinib therapy may result in dysregulated bone remodeling.
British Medical Bulletin · 2014 · 68 citations · open access
Myeloma bone disease: pathogenesis, current treatments and future targets
AbstractINTRODUCTION: Patients with myeloma develop localized and generalized bone loss leading to hypercalcaemia, accelerated osteoporosis, vertebral wedge fractures, other pathological fractures, spinal cord compression and bone pain. Bone loss is mediated by a variety of biological modifiers including osteoclast-activating factors (OAF) and osteoblast (OB) inhibitory factors produced either directly by malignant plasma cells (MPCs) or as a consequence of their interaction with the bone marrow microenvironment (BMM). Raised levels of OAFs such as receptor activator of nuclear factor-kappa B ligand (RANKL), macrophage inflammatory protein 1 alpha, tumour necrosis factor-alpha and interleukin 6 stimulate bone resorption by recruiting additional osteoclasts. Via opposing mechanisms, increases in OB inhibitory factors, such as dickkopf-1 (Dkk-1), soluble frizzled-related protein-3 and hepatocyte growth factor (HGF), suppress bone formation by inhibiting the differentiation and recruitment of OBs. These changes result in an uncoupling of physiological bone remodelling, leading to myeloma bone disease (MBD). Moreover, the altered BMM provides a fertile ground for the growth and survival of MPCs. Current clinical management of MBD is both reactive (to pain and fractures) and preventive, with bisphosphonates (BPs) being the mainstay of pharmacological treatment. However, side effects and uncertainties associated with BPs warrant the search for more targeted treatments for MBD. This review will summarize recent developments in understanding the intimate relationship between MBD and the BMM and the novel ways in which they are being therapeutically targeted. SOURCES OF DATA: All data included were sourced and referenced from PubMed. AREAS OF AGREEMENT: The clinical utility of BP therapy is well established. However, there is general acknowledgement that BPs are only partially successful in the treatment of MBD. The number of skeletal events attributable to myeloma are reduced by BPs but not totally eliminated. Furthermore, existing damage is not repaired. It is widely recognized that more effective treatments are needed. AREAS OF CONTROVERSY: There remains controversy concerning the duration of BP therapy. Whether denosumab is a viable alternative to BP therapy is also contested. Many of the new therapeutic strategies discussed are yet to translate to clinical practice and demonstrate equal efficacy or superiority to BP therapy. It also remains controversial whether reported anti-tumour effects of bone-modulating therapies are clinically significant. GROWING POINTS: The potential clinical utility of bone anabolic therapies including agents such as anti-Dkk-1, anti-sclerostin and anti-HGF is becoming increasingly recognized. AREAS TIMELY FOR DEVELOPING RESEARCH: Further research effectively targeting the mediators of MBD, targeting both bone resorption and bone formation, is urgently needed. This should translate promptly to clinical trials of combination therapy comprising anti-resorptives and bone anabolic therapies to demonstrate efficacy and improved outcomes over BPs.
Translational Oncology · 2019 · 39 citations · open access
Pazopanib in the Treatment of Bone Sarcomas: Clinical Experience
AbstractBACKGROUND: The effect of chemotherapy in metastatic bone sarcomas is poor and the condition is invariably fatal. Therefore, new treatment modalities are intensely needed. Pazopanib is a selective multitargeted tyrosine kinase inhibitor that has proven to be effective in the treatment of metastatic soft tissue sarcomas. The objective of this study was to evaluate the off-label use of pazopanib in patients with metastatic bone sarcomas who failed standard chemotherapy. METHODS: All patients with metastatic bone sarcomas treated with pazopanib between October 1st, 2011 and October 1st, 2017 at the Department of Oncology, Aarhus University Hospital were evaluated. Demographics, treatment, and survival outcomes were collected and analyzed. RESULTS: Nineteen patients were identified. The median age was 38 years (range 18-62). Most of the patients (50%) were diagnosed with osteosarcoma. All patients had documented disease progression at the time of initiating pazopanib treatment. The median overall survival was 11 months. Median progression free survival was 5.4 months. Out of 19 patients, 13 (68%) had either partial response or stable disease. In five patients, the dose of pazopanib was reduced because of toxicity. CONCLUSION: Off-label use of pazopanib is effective in the treatment of metastatic bone sarcomas of different histologies. Pazopanib was well tolerated in the treatment of patients with refractory bone sarcomas. Studies examining the effect of pazopanib alone or in combination with chemotherapy or other targeted therapies are needed.
AbstractSince the loss of bone tissue in osteoporosis appears to be permanent, the goals of treatment are to control the progress of the disease and prevent complications, while providing symptomatic relief to the patient. Appropriate medical intervention can retard, and in some cases even halt, the process, particularly if the condition is diagnosed before it becomes severely advanced.
The effect of combined drug therapy in lateral fragility fractures of the femur: a prospective observational study.
AbstractOBJECTIVE: Due to a growing number of lateral fragility fractures, and their high economic and social impact, we evaluated the combined drug therapy effectiveness in lateral fragility femur fractures treated by intramedullary nailing surgery comparing the clinical and radiological results of two groups of patients. PATIENTS AND METHODS: From May 2019 to March 2020, we carried out a prospective observational study comparing the results of patients with femoral lateral fractures treated by the same intramedullary nail (PFNA Synthes®) using Clodronic acid and Vitamin D (study group, 25 patients) compared to patients with the same fractures treated with Vitamin D alone (control group, 25 patients). The evaluations were based on bone biochemical markers (serum calcium level, serum phosphate level, parathyroid hormone, Vitamin D, serum C-terminal telopeptide), Visual Analogic Scale and HHS (Harris Hip Score) score, and femur densitometric views. In order to evaluate the femur neck mineral bone density (BMD), two areas have been identified on the Anterior-Posterior view: the Region of Interest (ROI)1 (under the head screw) and the ROI2 (above the femoral screw). The BMD has been calculated using femur densitometric views at T0 (1st day post-surgery) and at T1 (12 months later). RESULTS: As far as the BMD average of ROI1 is concerned, we found a significant statistical increase at T1 in the study group (0.93±0.07 gr/cm2) vs. control group (0.88±0.08 gr/cm2), p=0.04. Both biochemical and densitometric values were statistically increased in the study group from T0 to T1 (p<0.05), while control group showed an improvement in the biochemical values only. CONCLUSIONS: Thanks to a one year follow-up, we are able to demonstrate that the administration of an adequate drug therapy after surgery can lead to a better control of the bone remodeling and reabsorption process.
Dental and Medical Problems · 2021 · 7 citations · open access
Effect of metformin on the behavior of dental pulp stem cells cultured on freeze-dried bone allografts
AbstractBACKGROUND: Considering the complications associated with autogenous bone grafting, the use of freezedried bone allograft (FDBA) granules may be considered as an alternative treatment plan. OBJECTIVES: The aim of this study was to evaluate the effect of metformin on both the proliferation and osteogenic capability of dental pulp stem cells (DPSCs) cultured on FDBA granules. MATERIAL AND METHODS: First, a pilot study was conducted only on DPSCs to confirm cellular viability and the osteoinducing effect of 100 μmol/L metformin. Next, the cells were loaded on FDBA granules and treated with and without metformin. Finally, the following analyses were performed: scanning electron microscopy (SEM) (cell attachment); the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (proliferation); and alkaline phosphatase (ALP) activity analysis (osteogenic differentiation). RESULTS: The SEM images revealed that metformin enhanced the adhesion of DPSCs on FDBA granules. In addition, metformin was shown to increase cell proliferation/viability from day 1 to day 7. Compared to the control, a significant difference was observed after 7 days of treatment. Metformin enhanced the osteogenic capability of FDBA in both standard and osteoinducing conditions. An increase in ALP activity was significant after 7 days of treatment. The positive effect of metformin on differentiation was significant in osteoinducing conditions. CONCLUSIONS: Metformin can be applied as an additional osteoinductive factor in bone regeneration treatment. Moreover, scaffolds with controlled release of metformin can be considered a proper osteoinductive bone substitute that may lessen the complications related to applying allograft scaffolds alone.
The South African Orthopaedic Journal (SAOJ) · 2016 · 0 citations · open access
Cell signalling and bone remodelling Part II: Developments in the pathogenesis and principles of management of selected skeletal disease states
AbstractMapping of the bone remodelling signalling pathways contributed significantly to the establishment of a scientific basis for the development of pharmaceuticals which have the potential to induce or suppress bone formation. Enhancing bone healing and the establishment of a pre-determined skeletal phenotype are now within reach of the medical profession. This manuscript provides practitioners with an overview of recent developments in the quest for uncovering the molecular mechanisms involved in the pathogenesis of selected bone disease states and the role these discoveries play in the future management of bone healing and skeletal health.
[Research progress in the pathogenesis and treatment of craniofacial fibrous dysplasia].
AbstractCraniofacial fibrous dysplasia (CFD) is a rare skeletal disorder characterized by the abnormal replacement of normal bone tissue with fibrous tissue. This article provides a systematic review of the latest advancements in the genetic basis, molecular mechanisms, clinical manifestations, and diagnostic and therapeutic strategies of CFD. Elucidate, which leads to bone homeostasis imbalance and fibrotic abnormalities. It focuses on the molecular mechanisms underlying multi-pathway network dysregulation induced by GNAS gene mutations and explores the roles of key molecules like cAMP-response element binding protein, interleukin-6 and Fibroblast growth factor 23 in disease progression. Additionally, it evaluates the limitations of traditional treatments and the translational potential of novel strategies, including targeted therapies, offering a theoretical foundation for clinical practice and future research directions.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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