DeCure's autonomous Dermatology AI scientist is researching a drug-repurposing hypothesis for porokeratosis — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePorokeratosis maps to a 2-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 porokeratosis 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
phosphomevalonate kinase (PMVK) — PMVK 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3CH4 · 1.76 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Porokeratosis is a disorder of epidermal keratinization. A review of 281 cases in the English-language literature up to 1996 found that 21 (7.5%) had a malignancy arising within the porokeratosis. Large lesions, those of long duration, and the linear type carried the greatest risk. Radiation therapy was an infrequently identified risk factor. The authors concluded that porokeratosis is a premalignant condition.
In skin from seven patients, TUNEL-positive keratinocytes were observed in the epidermis underlying the cornoid lamella in all cases. Loricrin expression was interrupted there, while involucrin was expressed diffusely in the lesional epidermis. The authors suggested that abnormal early keratinocyte apoptosis accompanied by dysregulation of terminal differentiation may be involved in the pathogenesis.
A systematic review of drug-induced porokeratosis published in 2020 identified 26 patients from 25 studies. The most common therapies associated with development were biologic use, phototherapy, and radiotherapy. The most common clinical variants were the disseminated superficial or actinic types (60%), occurring in psoriasis patients undergoing phototherapy, and the eruptive disseminated type (24%), occurring in the context of biologic therapies. The Naranjo score ranged from possible to probable for the identified treatments. The authors called for large-scale studies to confirm the findings and explore pathogenesis.
What is still missing is a clear understanding of the molecular mechanism driving the abnormal keratinocyte apoptosis and dysregulation of differentiation, and whether that mechanism can be targeted. No controlled trial of any drug for porokeratosis has been reported. The drug-associated cases are few and the causal link is only possible or probable. Patient stratification by clinical variant or genetic background has not been attempted in a treatment study. Funding for a clinical trial remains absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Dermatologic Surgery · 1996 · 167 citations
Porokeratosis and Cutaneous Malignancy
AbstractBACKGROUND: Porokeratosis is a disorder of epidermal keratinization manifested clinically by a raised border and histologically by a cornoid lamella. While cutaneous malignancy has been reported to arise in porokeratosis, the risk remains unknown. In the past it has been associated with a history of radiation therapy. OBJECTIVE: The purpose of this study is to estimate the frequency of cutaneous malignancy arising in porokeratosis and define those patients who are at highest risk. METHODS: All cases in the English language literature in the last 30 years were reviewed. RESULTS: Twenty-one (7.5%) of 281 cases reported revealed a malignancy arising within porokeratosis. Large lesions, those of long-standing duration, and the linear type were at greatest risk. Radiation therapy was an infrequently identified risk factor. CONCLUSION: Porokeratosis is a premalignant condition, with certain groups of patients at greatest risk for malignant transformation.
British Journal of Dermatology · 2002 · 58 citations
Premature apoptosis of keratinocytes and the dysregulation of keratinization in porokeratosis
AbstractBACKGROUND: Porokeratosis is a dyskeratotic disorder of the skin characterized by cornoid lamella with parakeratosis, hyperkeratosis and loss of granular layers. The pathogenesis of porokeratosis and the mechanism(s) of its abnormal keratinization are still unknown. OBJECTIVE: To elucidate the mechanism(s) of abnormal keratinization that leads to the formation of cornoid lamellae in porokeratosis. METHODS: Apoptosis of keratinocytes was assessed in the skin of seven patients by an in situ apoptosis assay based on the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) reaction. Patterns of loricrin and involucrin expression were examined by immunohistochemistry. RESULTS: TUNEL-positive keratinocytes were observed in the epidermis underlying the cornoid lamella in all cases examined. Furthermore, loricrin expression was interrupted there, in contrast to involucrin, which was expressed diffusely in the lesional epidermis. CONCLUSIONS: These results suggest that an abnormal early keratinocyte apoptosis accompanied by dysregulation of terminal differentiation of those cells may be involved in the pathogenesis of porokeratosis.
AbstractThe coexistence of disseminated superficial actinic porokeratosis (DSAP) with other variants of porokeratosis is rare. We report three such cases: DSAP with porokeratosis of Mibelli; DSAP with linear porokeratosis; and DSAP occurring in the mother of a girl with linear porokeratosis. Although different areas of skin and different family members usually express the same morphological variant, we suggest that the simultaneous expression of two closely linked gene loci could explain the coexistence of different porokeratotic variants.
Drugs associated with development of porokeratosis: A systematic review
AbstractPorokeratosis is a rare disorder characterized by atrophic macules or patches, with a well-defined ridge-like hyperkeratotic border called cornoid lamella. Although the exact pathogenesis is unknown, drug associated cases have recently been reported in the literature. As such, we systematically reviewed and identified drugs associated with drug-induced porokeratosis, their resultant effects, and whether there was a casual relationship between the use of a drug and the development of porokeratosis. We searched for articles which reported drug-induced porokeratosis in MEDLINE and Embase in June 2020. After full-text review, 25 studies were included for analysis. We identified 26 patients with drug-induced porokeratosis. The most common therapies associated with development of porokeratosis is biologic use, phototherapy, and radiotherapy. The most common clinical variants were the disseminated superficial or actinic types (60%), which occurred in psoriasis patients undergoing phototherapy, and eruptive disseminated type (24%) which occurred in the context of biologic therapies. The Naranjo score ranged from possible to probable for the identified treatments. Clinicians should consider drug reactions as possible triggering events for porokeratosis, especially for patients taking biologics, phototherapy, and radiotherapy. Large-scale studies are required to confirm our findings and further explore the pathogenesis for drug-induced porokeratosis.
The Use of Fluor-Hydroxy Pulse Peel in Actinic Porokeratosis
AbstractBACKGROUND: The use of Fluor-Hydroxy pulse peel (Drogaderma, Sao Paulo, Brazil) was reported by Katz to treat solar damage and actinic keratosis-associated lesions. OBJECTIVE: The objective was to use this combined treatment to produce therapeutic and cosmetic benefits in a patient with actinic porokeratosis. METHODS: A case of actinic disseminated porokeratosis was treated with a combination of a 70% glycolic peel and a 5% 5-fluorouracil solution (Drogaderma) every 2 weeks for 4 months. A biopsy was done before and after eight treatment pulses. RESULTS: Improvement in the appearance and texture of the treated areas and decreased dyskeratosis and epidermal atypia. CONCLUSION: The Fluor-Hydroxy pulse peel can be an effective alternative for the treatment of actinic porokeratosis.
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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