DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for striate palmoplantar keratoderma — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleStriate palmoplantar keratoderma maps to a 3-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 striate palmoplantar keratoderma 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
keratin 1 (KRT1) — KRT1 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 bogdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6UUI · 2.069 Å · ligand octyl beta-D-glucopyranoside (BOG). Experimental structure, not a prediction.
What the evidence adds up to
In a 2015 case report, a single patient with refractory palmoplantar keratoderma was treated with alitretinoin; the abstract provides no numerical outcome data, no sample size beyond that one patient, and no controlled comparison. A 2002 study of five members of a Jewish family with epidermolytic palmoplantar keratoderma identified a mutation in codon 160 of exon 1 of the keratin 9 gene, consistent with findings in most other families with the same clinical features. No treatment or drug was tested in that study.
A 2019 cross-sectional study of 106 patients with palmoplantar keratoderma attending a dermatology outpatient department found that the majority were between the second and fourth decades of life (65%). Housewives (30.1%) and daily wage labourers (24.5%) were the most common occupations among those with acquired PPK. Associated conditions included psoriasis (52.8%), eczema (15.09%), pityriasis rubra pilaris (8.4%), and erythroderma dermatitis (5.6%). The study reported a notable impact on quality of life in 57.4% of cases, but did not test any drug intervention.
A 2021 systematic review of drug-induced palmoplantar keratoderma analysed 40 studies covering 247 patients (mean age 57.0 years; 60.3% male where sex was reported). PPK most frequently developed after treatment with BRAF inhibitors (73.7% of cases, 182/247), BRAF inhibitors combined with MEK1/2 inhibitors (15.4%, 38/247), tyrosine kinase inhibitors (3.2%, 8/247), or chemotherapy (2.4%, 6/247). The mean latency from drug initiation to PPK onset was 7.6 months (range 0.25–90 months). Improvement was reported in 24 cases: 12 achieved complete resolution and 12 partial resolution. All patients with complete resolution had stopped the suspected drug, with a mean resolution period of 2.4 months (range 2 weeks–6 months). The most common treatments for the PPK itself were keratolytic treatments (10 cases) and topical corticosteroids (4 cases). The review does not report any trial of alitretinoin or other systemic retinoids for drug-induced PPK.
What remains missing is any randomised controlled trial of alitretinoin for hereditary or acquired palmoplantar keratoderma, any validated patient stratification by genotype or drug trigger, and any funding for such a trial. The evidence for drug-induced PPK is limited to retrospective case series with no standardised outcome measures.
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 Dermatology · 2015 · 10 citations
Alitretinoin: treatment for refractory palmoplantar keratoderma
AbstractJournal Article Alitretinoin: treatment for refractory palmoplantar keratoderma Get access H.K. Park, H.K. Park Department of Dermatology Hanyang University College of Medicine Seoul 133‐792 South Korea Search for other works by this author on: Oxford Academic Google Scholar E.J. Kim, E.J. Kim Department of Dermatology Hanyang University College of Medicine Seoul 133‐792 South Korea Search for other works by this author on: Oxford Academic Google Scholar J.Y. Ko J.Y. Ko Department of Dermatology Hanyang University College of Medicine Seoul 133‐792 South Korea Correspondence: Joo Yeon Ko. E‐mail: [email protected] Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 174, Issue 5, 1 May 2016, Pages 1143–1144, https://doi.org/10.1111/bjd.14327 Published: 01 May 2016
Journal of the European Academy of Dermatology and Venereology · 2002 · 3 citations
Keratin‐9 gene mutation in a family with epidermolytic palmoplantar keratoderma
AbstractBACKGROUND: Epidermolytic palmoplantar keratoderma is an autosomal dominant inherited disorder of keratinization. METHODS: We studied five members of a Jewish family with epidermolytic palmoplantar keratoderma. Genomic DNA was extracted from leucocytes, and exon 1 of the keratin 9 gene was amplified using polymerase chain reaction techniques. RESULTS: The mutation was found in exon 1 of the keratin 9 gene in codon 160. CONCLUSIONS: Like most of the other families with clinical features of epidermolytic palmoplantar keratoderma the mutation is found in exon 1 of the keratin 9 gene.
IP Indian Journal of Clinical and Experimental Dermatology · 2019 · 1 citations · open access
Assessment of clinical manifestations related to palmoplantar keratoderma and its impact on quality of life of cases
AbstractIntroduction: Palmoplantar keratodermas (PPKs) is heterogeneous entity of cutaneous disorders, with hyperkeratinisation of stratum corneum over palm and soles. PPKs can be hereditary or acquired. Acquired PPK occurs in later years due to continuous or constant exposure to allergens, irritants and exposure to trauma. Aim: This study undertaken to assess the clinical manifestations related to Palmoplantar keratoderma cases and its impact on quality of life of cases. Materials and Methods: A total of 106 patients with chief complaints of Palmoplantar keratoderma attending outpatient department of DVL were included. Detailed clinical history regarding diseases status was collected. The Patients feedback was taken as impact scores i.e. 3 (Very good), 2 (Good), 1 (Moderate), 0 (Poor). QOL was measured by grading system based on the patient’s feedback. Results: Majority cases were between 2nd to 4th decades (65%). Housewives (30.1%) and daily wage labourers (24.5%) were more commonly affected by acquired PPK. Psoriasis (52.8%) followed by Eczema (15.09%), Pityriasis rubra pilaris (8.4%) and Erythroderma dermatitis (5.6%) are common symptoms associated with PPK. There is a notable impact of PPK on quality of life of patients in 57.4% cases. Conclusion: Acquired PPK is always misdiagnosed because it is nonhereditary. House wives and daily wage workers are commonly affected due to constant exposure to detergents, chemicals and various forms of trauma. Palmoplantar keratodermas has remarkable impact on quality of life of patients. Keywords: Palmoplantar keratoderma (PPK), Psoriasis, Occupation, Prevalence, Quality of life (QOL).
Sage Journals Data · 2021 · 0 citations · open access
Drugs Associated With the Development of Palmoplantar Keratoderma: A Systematic Review
AbstractBackgroundPalmoplantar keratoderma (PPK) are a heterogenous group of hereditary and acquired disorders that are characterized by excessive epidermal thickening of the palms and/or soles. PPK has been described as a rare adverse event for some medications. The aim of this systematic review was to summarize outcomes in PPK associated with various medications. This data will assist dermatologists and other healthcare providers treating patients with drug-induced PPK.MethodsEMBASE and MEDLINE databases were searched in accordance with PRISMA guidelines using the keyword “palmoplantar keratoderma.” 40 studies met the inclusion criteria.ResultsA total of 247 patients (mean age: 57.0 years) were included in the analysis. Among patients whose sex was reported, 60.3% (<i>n</i> = 35/58) were male. PPK most frequently developed after treatment with BRAF inhibitors (73.7%, <i>n</i> = 182/247), BRAF inhibitors combined with MEK1/2 inhibitors (15.4%, <i>n</i> = 38/247), tyrosine kinase inhibitors (TKIs) (3.2%, <i>n</i> = 8/247), or chemotherapy (2.4%, <i>n</i> = 6/247). The mean latency period between initiation of the drug and onset of PPK was 7.6 months (range: 0.25-90 months). Improvement of PPK was reported in 24 cases, with 50% (<i>n</i> = 12/24) achieving complete resolution and 50% (<i>n</i> = 12/24) achieving partial resolution. All patients who achieved complete resolution stopped the suspected drug, with a mean resolution period of 2.4 months (range: 2 weeks-6 months). The most common treatments for PPK were keratolytic treatments (<i>n</i> = 10) and topical corticosteroids (<i>n</i> = 4).ConclusionsPPK was most frequently associated with targeted kinase inhibitors, specifically BRAF, MEK1/2, and tyrosine kinase inhibitors.
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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