DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for brachydactyly type A2 — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBrachydactyly type A2 maps to a 5-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
No approved-drug candidate for brachydactyly type a2 is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
bone morphogenetic protein receptor type 1B (BMPR1B) — BMPR1B is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 4-piperazin-1-ylphenyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3MDY · 2.05 Å · ligand 4-[6-(4-piperazin-1-ylphenyl)pyrazolo[1,5-a]pyrimidin-3-yl]quinoline (LDN). Experimental structure, not a prediction.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Genetics · 2009 · 77 citations
The brachydactylies: a molecular disease family
AbstractBrachydactyly refers to shortening of the hands and/or feet due to missing, deformed, or shortened bones. It may occur as an isolated trait or as part of a syndrome. According to their pattern of skeletal involvement, the isolated brachydactyly forms have been categorized in the groups A-D including several subgroups. As in many other genetic conditions, there is considerable phenotypic overlap between the groups. The identification of the molecular causes of these conditions has offered insights into their pathogenesis. The generation of animal models has facilitated research on the pathogenic events during digit development that lead to the brachydactyly phenotype. These studies have shown that the BMP pathway plays a pivotal role in the normal development of digits and joints and that the majority of brachydactyly disease genes are directly or indirectly linked to this pathway. Together, these genes function in a regulatory network which is deregulated in the disease state. As a consequence of the close interactions within the network, overlapping phenotypes are generated that are, nevertheless, characterized by specific recognizable patterns. This principle does not only apply for the brachydactylies but is also valid for many other disease entities. Groups of diseases that show a common phenotypic pattern due to the deregulation of a molecular network are suggested to be called molecular disease families.
uO Research (University of Ottawa) · 2015 · 0 citations · open access
The Genetic Heterogeneity of Brachydactyly Type A1: Identifying the Molecular Pathways
AbstractBrachydactyly type A1 (BDA1) is a rare autosomal dominant trait characterized by the shortening of the middle phalanges of digits 2-5 and of the proximal phalange of digit 1 in both hands and feet. Many of the brachymesophalangies including BDA1 have been associated with genetic perturbations along the BMP-SMAD signaling pathway. The goal of this thesis is to identify the molecular pathways that are associated with the BDA1 phenotype through the genetic assessment of BDA1-affected families. We identified four missense mutations that are clustered with other reported BDA1 mutations in the central region of the N-terminal signaling peptide of IHH. We also identified a missense mutation in GDF5 cosegregating with a semi-dominant form of BDA1. In two families we reported two novel BDA1-associated sequence variants in BMPR1B, the gene which codes for the receptor of GDF5. In 2002, we reported a BDA1 trait linked to chromosome 5p13.3 in a Canadian kindred (BDA1B; MIM %607004) but we did not discover a BDA1-causal variant in any of the protein coding genes within the 2.8 Mb critical region. To provide a higher sensitivity of detection, we performed a targeted enrichment of the BDA1B locus followed by high-throughput sequencing. We report the identification of a novel 9.5 Kb intergenic tandem duplication in two unrelated BDA1-affected families. In-vitro and in-vivo reporter assays demonstrated the enhancer activity of noncoding conserved sequence elements found within the microduplication. We also show an upregulation of the neighboring genes, NPR3 and PDZD2, in the patients' fibroblasts that suggests a gain-of-function through the duplication of cis-regulatory elements on dose sensitive genes. By expanding the repertoire of BDA1-causing mutations in IHH, GDF5, BMPR1B and at the BDA1B locus, we have begun to elucidate a common genetic pathway underlying phalangeal formation and elongation.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
