DeCure's autonomous Dermatology AI scientist is researching a drug-repurposing hypothesis for keratosis — 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 moduleKeratosis 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 keratosis 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
retinoid X receptor beta (RXRB) — RXRB 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 plmdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7A78 · 1.72 Å · ligand PALMITIC ACID (PLM). Experimental structure, not a prediction.
What the evidence adds up to
In a 2008 open-label randomised trial of 49 patients with actinic keratosis, 3% diclofenac sodium gel applied once daily was compared with 5% imiquimod cream applied three times a week, both for 12 weeks. According to the Investigator Global Improvement Index, a complete response was observed in 12% of the diclofenac group and 22% of the imiquimod group. By the Patient Global Improvement Index, a complete response was seen in 28% of the diclofenac group and 23% of the imiquimod group. The differences between the two groups were not statistically significant (p > 0.05). The authors concluded that complete remission was very low for both drugs and that topical treatments with these agents were not completely effective.
A 2003 summary of three clinical trials of imiquimod 5% cream for actinic keratosis reported a reasonable efficacy rate and a high safety profile. The summary suggested that cycle therapy might improve the safety profile while maintaining efficacy, and that field treatment with imiquimod might uncover and treat subclinical actinic keratoses, potentially resulting in fewer recurrences. The authors noted that longer follow-up studies were required to investigate this possibility.
A 2002 study examined the expression of the serine protease neuropsin (KLK8) in normal and pathological skin samples. Weak signals for KLK8 mRNA were seen in normal skin, localised to superficial cells beneath the cornified layer. Skin samples from psoriasis vulgaris, seborrheic keratosis, lichen planus, and squamous cell carcinoma — all showing severe hyperkeratosis — displayed a high density of KLK8 mRNA. The signals were localised in granular and spinous layers of lesional skin. In cell culture, when keratinisation proceeded in high calcium medium, a correlative increase in KLK8 mRNA expression was observed. The authors concluded that the results were consistent with a role for this protease in the terminal differentiation of keratinocytes.
What is still missing: larger randomised trials with longer follow-up to assess recurrence rates after imiquimod field treatment; direct comparisons of imiquimod with other topical agents beyond the single small 2008 study; and any clinical trial testing whether modulation of KLK8 expression could alter the course of keratosis. No trial has yet stratified patients by lesion subtype, location, or immune status to identify who might benefit.
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 Dermatological Treatment · 2008 · 52 citations
Comparison of the efficacy and tolerability of 3% diclofenac sodium gel and 5% imiquimod cream in the treatment of actinic keratosis
AbstractBACKGROUND: Topical diclofenac and imiquimod have been reported to be effective in the treatment of actinic keratosis, but a study to compare these two drugs has not been reported yet. OBJECTIVE: To compare the efficacy and safety of topical 3% diclofenac gel plus hyaluronic acid and 5% imiquimod cream in the treatment of actinic keratosis. METHODS: Forty-nine patients with actinic keratosis were enrolled in this randomized comparative open-label study. Twenty-four patients applied 3% diclofenac gel once a daily to their lesions, while the other 25 patients were treated with a 5% imiquimod cream three times a week for 12 weeks. Patients were examined before treatment and every month of the treatment. Assessments were made by investigators according to the Investigator and the Patient Global Improvement Indices (IGII) and (PGII). RESULTS: According to the IGII results, a complete response was observed in 12% of the diclofenac group and 22% of the imiquimod group. For the PGII scores, a complete response was observed in 28% of the diclofenac group and 23% of the imiquimod group. There were no significant differences between the two groups (p > 0.05). Both treatments were well tolerated, with most adverse events related to skin. CONCLUSION: The two drugs were found to be equally effective and safe in the treatment of actinic keratosis but complete remission was very low. Therefore, topical treatments with these two drugs were not seen to be completely effective, and combined therapies and further studies are needed.
Epidermal expression of serine protease, neuropsin (KLK8) in normal and pathological skin samples
AbstractAIMS: The expression of human neuropsin (KLK8) mRNA in normal and pathological skin samples was analysed and the results compared with those for tissue plasminogen activator (tPA) mRNA. METHODS: Northern blot and in situ hybridisation analyses of KLK8 mRNA in normal and lesional skin of patients with cutaneous diseases were performed. RESULTS: A weak signal for KLK8 mRNA and no signal for tPA mRNA was seen in normal skin on northern blot analysis. Weak signals for KLK8 were localised to the superficial cells beneath the cornified layer in normal skin on in situ hybridisation. Psoriasis vulgaris, seborrheic keratosis, lichen planus, and squamous cell carcinoma skin samples, which show severe hyperkeratosis, displayed a high density of KLK8 mRNA on northern and in situ hybridisation analyses. The signals were localised in granular and spinous layers of lesional skin in all hyperkeratic samples, including the area surrounding the horn pearls of squamous cell carcinoma. To examine the relation between mRNA expression and terminal differentiation, the expression of KLK8 mRNA was analysed in cell cultures. When keratinisation proceeded in high calcium medium, a correlative increase in the expression of KLK8 mRNA was observed. CONCLUSION: The results are consistent with a role for this protease in the terminal differentiation of keratinocytes.
British Journal of Dermatology · 2003 · 31 citations
Summary of actinic keratosis studies with imiquimod 5% cream
AbstractImiquimod is being investigated as a therapeutic option for the management of actinic keratosis. Three recent clinical trials have demonstrated a reasonable efficacy rate and high safety profile. 'Cycle' therapy may improve the safety profile while maintaining efficacy. 'Field' treatment with imiquimod may uncover and treat 'subclinical' actinic keratoses, which in turn may potentially result in fewer recurrences. Longer follow-up studies are required to investigate this possibility.
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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