DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for pterygium — screening already-approved drugs against its 10-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePterygium maps to a 10-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 pterygium 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
histamine receptor H1 (HRH1) — HRH1 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 hsmdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8YN2 · 2.66 Å · ligand HISTAMINE (HSM). Experimental structure, not a prediction.
What the evidence adds up to
Seven pterygium specimens showed nuclear immunoreactivity for cyclin D1 and Ki-67 in many epithelial cells, while p27(KIP1) was positive in only a few epithelial cells; the stroma hardly stained for any of these markers. In three normal conjunctivas, p27(KIP1) was noted in many epithelial cells, with cyclin D1 and Ki-67 positive nuclei intermingled. A separate study of ten pairs of pterygium and normal conjunctiva found no statistical difference in the number of p63-positive cells (P = 0.7), and the authors concluded that pterygium arises from incorrect control of apoptosis rather than increased proliferative capacity. A 2019 analysis of mRNA expression profiles identified 557 differentially expressed genes between pterygium and normal conjunctiva, with FN1, PRSS23, ABCA1, KRT6A, ECT2 and SPARC significantly up-regulated by qRT-PCR validation.
A meta-analysis of nine randomised controlled trials involving 474 patients (482 eyes) found that topical or subconjunctival bevacizumab had no statistically significant effect on preventing pterygium recurrence (relative risk 0.90, 95% CI 0.77–1.07, P = 0.23). Subgroup analyses for surgery versus non-surgery and primary versus recurrent pterygium all yielded non-significant results. Bevacizumab was associated with a higher risk of subconjunctival haemorrhage (RR 3.34, 95% CI 1.07–10.43, P = 0.04). In a prospective randomised trial of 60 patients with primary pterygium, a single intraoperative application of 0.02% daunorubicin for three minutes produced a recurrence rate of 6.67% compared to 33% in the control group receiving distilled water; chemosis and delayed epithelisation were the only complications noted over a mean follow-up of 15 months.
A 2025 study reported that Bacillus coagulans isolated from pterygium patient tears promoted proliferation of human conjunctival epithelial cells while inhibiting pterygium fibroblast proliferation in vitro. The effect was mediated by bacterial extracellular vesicles and involved the p53/CDKN1A signalling pathway, as shown by transcriptomic sequencing and use of the SIRT2-IN-11 inhibitor. The relevance of these findings to human pterygium treatment has not been tested.
What is still missing is a large-scale trial of daunorubicin with longer follow-up to confirm its safety and efficacy, and any clinical trial of the bacterial extracellular vesicle approach. No drug has been shown to reverse or shrink existing pterygium in patients. Patient stratification by pterygium subtype or molecular profile has not been attempted in any of the intervention 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.
British Journal of Ophthalmology · 2006 · 53 citations · open access
Expression of p27(KIP1) and cyclin D1, and cell proliferation in human pterygium
AbstractBACKGROUND: The pterygium is a growth onto the cornea of fibrovascular tissue that is continuous with the conjunctiva, whereas the mechanisms of cell proliferation in pterygium epithelium are unknown. AIM: To analyse the histopathology and the expression of cell cycle-related molecules in pterygium tissues. METHODS: Seven pterygia were surgically removed using the bare-sclera procedure, and three normal bulbar conjunctivas were also obtained. Formalin-fixed, paraffin-wax-embedded tissues were analysed by immunohistochemistry with anti-p27(KIP1), cyclin D1 and Ki-67 antibodies. RESULTS: Conjunctival epithelium consisted of several layers of round cells with a few goblet cells. Nuclear immunoreactivity for p27(KIP1) was noted in many normal epithelial cells, where cyclin D1 and Ki-67-positive nuclei were intermingled. A variety of goblet cells were located in the superficial layer of the pterygium head as well as those of the body epithelia. Several pterygium epithelial cells were p27(KIP1) positive, whereas nuclear immunoreactivity for cyclin D1 and Ki-67 was detected in many epithelial cells. By contrast, immunoreactivity for p27(KIP1), cyclin D1 and Ki-67 was hardly detected in the pterygium stroma. CONCLUSION: It is suggested that pterygium growth and development are associated with the proliferation of epithelium, which is possibly involved in the expression of cell cycle-related molecules.
AbstractPURPOSE: The aim of this study was to assess the efficacy and safety of bevacizumab in the treatment of pterygium and to mainly explore its effects on recurrence rate and complications. METHODS: We searched MEDLINE, EMBASE, Web of Science, and Cochrane Central Register from the inception to July 2013 for relevant randomized controlled trials that examined bevacizumab therapy for pterygium. Data concerning study design, patient characteristics, treatment, and outcomes were extracted. The methodological quality of the studies included was assessed using the Jadad score. Relative risk (RR) was calculated for recurrence rate and complications. RESULTS: A total of 474 patients with 482 eyes in 9 randomized controlled trials were analyzed. The pooled estimate showed that bevacizumab had no statistically significant effect on preventing pterygium recurrence [RR 0.90, 95% confidence interval (CI) 0.77-1.07, P = 0.23]. None of the subgroup analyses yielded significant results in favor of bevacizumab (surgery group: RR 0.77, 95% CI 0.50-1.18, P = 0.23; nonsurgery group: RR 0.98, 95% CI 0.86-1.11, P = 0.76; primary pterygium group: RR 0.82, 95% CI 0.53-1.26, P = 0.36; recurrent pterygium group: RR 0.95, 95% CI 0.82-1.09, P = 0.44). There were no statistically significant differences in the complications between the 2 groups (RR 1.00, 95% CI 0.73-1.37, P = 1.00). However, the bevacizumab group was associated with a higher risk of developing subconjunctival hemorrhage (RR 3.34, 95% CI 1.07-10.43, P = 0.04). CONCLUSIONS: Topical or subconjunctival bevacizumab was relatively safe and well tolerated, but it had no statistically significant effect on preventing pterygium recurrence. A large-scale trial with a suitable dosage and a longer follow-up would be required to rule out the possibility of any treatment benefit.
Expression of p63 in Pterygium and Normal Conjunctiva
AbstractPURPOSE: The p63 gene has been identified as a marker of epithelial stem cells. Because pterygium may arise through an expansion of the proliferative capacity of the conjunctiva, we sought to document the expression of p63 in normal conjunctiva and pterygium specimens. METHODS: Immunostaining for p63 expression was performed on 10 pairs of pterygium and normal conjunctiva using a monoclonal antibody directed against human p63. RESULTS: Immunopositive reactions were seen in all samples. Levels of p63-positive cells were not statistically different between pterygium and normal conjunctivae (P = 0.7). CONCLUSION: These results strongly support previous studies that indicate that pterygium arises as a result of incorrect control of cellular apoptosis rather than from an increase in proliferative capacity.
Intraoperative Daunorubicin to Prevent the Recurrence of Pterygium After Excision
AbstractPURPOSE: This study examines the safety, efficacy, and complications of 0.02% intraoperative daunorubicin in the prevention of the recurrence of pterygium after excision. METHODS: Sixty patients with primary pterygium were included in this prospective, randomized clinical study and were randomly divided into two groups: the treatment group and the control group. Pterygium was excised under a microscope in all patients. The treatment group received intraoperative single application of 0.02% daunorubicin for 3 minutes, whereas the control group received distilled water for the same duration. Recurrence of pterygium and postoperative complications were prime areas of interest. RESULTS: A recurrence rate of 6.67% was seen in the treatment group and was 33% in the control group. Chemosis of conjunctiva and delayed epithelization were the only complications noticed after a mean follow-up of 15 months. CONCLUSION: Initial results indicate that a single intraoperative application of 0.02% daunorubicin for 3 minutes appears to be a safe and effective adjunct therapy to prevent the recurrence of pterygium. However, a much larger cohort study over a considerable number of years will eventually demonstrate the safety.
International Journal of Ophthalmology · 2019 · 13 citations · open access
Identification of pathogenic genes of pterygium based on the Gene Expression Omnibus database
AbstractAIM: To identify the pathogenic genes in pterygium. METHODS: We obtained mRNA expression profiles from the Gene Expression Omnibus database (GEO) to identify differentially expressed genes (DEGs) between pterygium tissues and normal conjunctiva tissues. The Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis, protein-protein interaction (PPI) network and transcription factors (TFs)-target gene regulatory network was performed to understand the function of DEGs. The expression of selected DEGs were validated by the quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: A total of 557 DEGs were identified between pterygium and normal individual. In PPI network, several genes were with high degrees such as FN1, KPNB1, DDB1, NF2 and BUB3. SSH1, PRSS23, LRP5L, MEOX1, RBM14, ABCA1, JOSD1, KRT6A and UPK1B were the most downstream genes regulated by TFs. qRT-PCR results showed that FN1, PRSS23, ABCA1, KRT6A, ECT2 and SPARC were significantly up-regulated in pterygium and MEOX1 and MMP3 were also up-regulated with no significance, which was consistent with the our integrated analysis. CONCLUSION: The deregulated genes might be involved in the pathology of pterygium and could be used as treatment targets for pterygium.
<i>Bacillus Coagulans</i> Secretes Extracellular Vesicles and Modulates the Proliferation of Conjunctival Epithelial Cells via the P53/CDKN1A Signaling Pathway
AbstractPURPOSE: 16S rRNA sequencing and evaluate their impact on human conjunctival epithelial cells (HConEpics) and pterygium fibroblasts (HPFs) proliferation. METHODS: Tear samples were cultured aerobically and anaerobically on blood agar plates. Bacterial colonies were characterized by 16S rRNA sequencing. Proliferation of HConEpics and HPFs was assessed using CCK-8 and EDU assays. The role of bacterial extracellular vesicles (EVs) was explored using the exosome inhibitor GW4869. EVs were isolated and characterized by transmission electron microscopy and nanoparticle tracking analysis (NTA), with DIL staining confirming their internalization by host cells. Transcriptomic sequencing and the SIRT2-IN-11 inhibitor were used to elucidate the molecular mechanisms and regulatory pathways. RESULTS: (BC) in pterygium patients. BC significantly promoted HConEpics proliferation while inhibiting HPFs proliferation. GW4869 significantly reduced the stimulatory effect of BC culture supernatant on HConEpics proliferation, confirming EVs-medicated regulation. BC-derived EVs, isolated by ultracentrifugation, were internalized by HConEpics, promoting proliferation and inducing G1 phase cell cycle accumulation. These EVs also inhibited TGF-β-induced damage to HConEpics. Transcriptomic sequencing identified the p53 pathway as a key regulatory pathway, further clarified by SIRT2-IN-11. CONCLUSIONS: This study offers novel insights into pterygium pathogenesis and identifies potential therapeutic targets.
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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