DeCure's autonomous Respiratory AI scientist is researching a drug-repurposing hypothesis for pulmonary fibrosis — screening already-approved drugs against its 35-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePulmonary fibrosis maps to a 35-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
approvedSunitinibApproved drug
Structures already discussed alongside pulmonary fibrosis in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
KIT kinase domain — Sunitinib has a real, experimentally solved structure in complex with this target (PDB 3G0E, 1.6 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 b49drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3G0E · 1.6 Å · ligand Sunitinib (B49). Experimental structure, not a prediction.
What the evidence adds up to
Idiopathic pulmonary fibrosis is a chronic progressive lung disease with a prognosis that can be worse than for many cancers. Two drugs, pirfenidone and nintedanib, are approved and slow progression, but they do not improve the condition. The prognosis remains poor. Many other drugs have failed in clinical trials. Nonpharmacologic approaches such as long-term oxygen therapy, pulmonary rehabilitation, and lung transplantation are additional treatment modalities.
In a 2016 mouse study, sunitinib, a small-molecule multi-targeted tyrosine kinase inhibitor, was tested against bleomycin-induced pulmonary fibrosis. Mice that received bleomycin showed destruction of pulmonary architecture, proliferation of fibroblasts, and extensive collagen deposition. Sunitinib attenuated the fibrosis and inhibited fibroblast accumulation in the lung. In cell experiments using human bronchial epithelial cells and W138 human lung fibroblasts, sunitinib suppressed the degree of epithelial-to-mesenchymal transition induced by TGF-β and reduced the proliferation of fibroblasts. It also reduced the phosphorylation of serine residues on Smad2/3 induced by TGF-β. These are mouse and cell data only.
A 2018 review of early stage clinical trials notes that a key challenge is deciding which compounds to combine and how to evaluate combination therapies. The drugs most likely to provide additive efficacy when used with one of the approved therapies are those with alternative, complementary, or synergistic mechanisms of action. The review lists numerous clinical trial identifiers but provides no efficacy results from those trials.
What is still missing is evidence from human trials that any repurposed drug improves survival or lung function in pulmonary fibrosis. The mouse data for sunitinib has not been confirmed in patients. The field lacks a clear strategy for patient stratification and the funding to run the large, long-term trials needed to detect a meaningful benefit in a disease that already has two approved but only partially effective drugs.
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 Medicine Insights Circulatory Respiratory and Pulmonary Medicine · 2015 · 80 citations · open access
Idiopathic Pulmonary Fibrosis: Treatment and Prognosis
AbstractIdiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with a prognosis that can be worse than for many cancers. The initial stages of the condition were thought to mainly involve chronic inflammation; therefore, corticosteroids and other drugs that have anti-inflammatory and immunosuppressive actions were used. However, recently, agents targeting persistent fibrosis resulting from aberrant repair of alveolar epithelial injury have been in the spotlight. There has also been an increase in the number of available antifibrotic treatment options, starting with pirfenidone and nintedanib. These drugs prevent deterioration but do not improve IPF. Therefore, nonpharmacologic approaches such as long-term oxygen therapy, pulmonary rehabilitation, and lung transplantation must be considered as additional treatment modalities.
Expert Opinion on Investigational Drugs · 2018 · 20 citations
Therapeutic targets and early stage clinical trials for pulmonary fibrosis
AbstractIntroduction: Idiopathic pulmonary fibrosis (IPF) is an age-associated, progressive, and irreversible fatal interstitial lung disease. Although many drugs have failed in clinical trials, these failures improved the understanding of the pathogenesis of IPF. Currently, there are two drugs approved for IPF that slow the progression of the disease. However, the prognosis for patients with IPF remains poor and the search continues for drugs that inhibit the pathogenic pathways active in IPF to further reduce or even halt the progression of the disease.Areas covered: We highlight the recent information on the therapeutic targets currently explored in early stage clinical trials and discuss the potential for new therapy and the limitation of basic research in the treatment of IPF.Expert opinion: A key challenge in the coming years will lie in deciding which compounds to combine and how to evaluate combination therapies in clinical trials. The drugs most likely to provide additive efficacy when used in combination with one of the approved therapies are those with alternative, complementary, or synergistic mechanisms of action.Trial registration: ClinicalTrials.gov identifier: NCT02257177.Trial registration: ClinicalTrials.gov identifier: NCT02738801.Trial registration: ClinicalTrials.gov identifier: NCT02538536.Trial registration: ClinicalTrials.gov identifier: NCT02503657.Trial registration: ClinicalTrials.gov identifier: NCT01371305.Trial registration: ClinicalTrials.gov identifier: NCT02550873.Trial registration: ClinicalTrials.gov identifier: NCT02688647.Trial registration: ClinicalTrials.gov identifier: NCT01872689.Trial registration: ClinicalTrials.gov identifier: NCT01529853.Trial registration: ClinicalTrials.gov identifier: NCT02345070.Trial registration: ClinicalTrials.gov identifier: NCT01629667.Trial registration: ClinicalTrials.gov identifier: NCT01890265.Trial registration: ClinicalTrials.gov identifier: NCT01262001.Trial registration: ClinicalTrials.gov identifier: NCT03142191.Trial registration: ClinicalTrials.gov identifier: NCT02036970.Trial registration: ClinicalTrials.gov identifier: NCT00463983.Trial registration: Japan Primary Registries Network identifier: JapicCTI-183898.
The Tohoku Journal of Experimental Medicine · 2016 · 20 citations · open access
Sunitinib, a Small-Molecule Kinase Inhibitor, Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice
AbstractIdiopathic pulmonary fibrosis (IPF) is a chronic and ultimately fatal disease, characterized by excessive accumulation of fibroblasts, extensive deposition of extracellular matrix, and destruction of alveolar architecture. IPF is associated with an epithelial-dependent fibroblast-activated process, termed the epithelial-to-mesenchymal transition (EMT). However, there is still a lack of strategies to target EMT for the treatment of IPF. Sunitinib, a small-molecule multi-targeted tyrosine kinase inhibitor, targets multiple kinases that may play an important role in developing pulmonary fibrosis. Here, we explored the therapeutic potential of sunitinib using a mouse model of pulmonary fibrosis. Mice received intratracheal instillation of bleomycin (BLM). Then, the mice were intragastrically administrated with sunitinib or normal saline until the end of the experiment. Distinguished destruction of pulmonary architecture, conspicuous proliferation of fibroblasts and extensive deposition of collagen fibers were found in BLM mice. Sunitinib attenuated the pulmonary fibrosis and inhibited the accumulation of fibroblasts in the lung of BLM mice. To investigate if the inhibition of fibroblast accumulation in the lung by sunitinib was associated with EMT, we used human bronchial epithelial cells (HBEs) and W138 human lung fibroblasts. Sunitinib suppressed the degree of EMT induced by TGF-β, a profibrotic factor, in HBEs and the proliferation of WI38 fibroblasts. Moreover, sunitinib reduced the degree of phosphorylation of serine residues on Smad2/3 that was induced by TGF-β in HBEs. As EMT and accumulation of fibroblasts are critical for the development of pulmonary fibrosis, targeting multiple pro-fibrosis signaling pathways with sunitinib may be a novel strategy to treat pulmonary fibrosis.
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.
