DeCure's autonomous Dermatology AI scientist is researching a drug-repurposing hypothesis for dermatitis — screening already-approved drugs against its 42-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDermatitis maps to a 42-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 dermatitis 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
neutrophil cytosolic factor 4 (NCF4) — NCF4 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 butanoyloxydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1H6H · 1.7 Å · ligand 2-(BUTANOYLOXY)-1-{[(HYDROXY{[2,3,4,6-TETRAHYDROXY-5-(PHOSPHONOOXY)CYCLOHEXYL]OXY}PHOSPHORYL)OXY]METHYL}ETHYL
BUTANOATE (PIB). Experimental structure, not a prediction.
What the evidence adds up to
The 2021 review on atopic dermatitis states that the disease is chronic, relapsing, and multifactorial, with genetic predisposition, immune dysfunction, and environmental provocation factors all contributing. It notes that the increasing prevalence of AD points to environmental factors such as irritation and cutaneous infection as crucial triggers or aggravators. AD skin is susceptible to bacterial, fungal and viral infections, and microorganisms can colonise the skin and worsen symptoms. The review calls for understanding how these risk factors affect cutaneous immunity to develop a precision medicine approach, but it does not report any new trial results or quantitative outcomes.
A 2016 genetic study of 536 health care workers examined single nucleotide polymorphisms in genes related to inflammation, skin barrier integrity, signalling, and antioxidant defence. Subjects were patch tested with sodium lauryl sulfate, sodium hydroxide, and benzalkonium chloride. SNPs in ACACB, NTRK2, NTRK3, IL22, PLAU, EGFR, and FGF2 showed association with skin response to the irritants at P < 0.001. SNPs in EGF, EGFR, CXCL12, and VCAM1 were associated with hand dermatitis at P < 0.005. The authors conclude that genetic variation in inflammation and skin homeostasis genes can influence irritant responses and may explain inter-individual variation in contact dermatitis development. No treatment or drug was tested.
A 2022 review discusses caspase recruitment domain-containing proteins and dermatoses. It reports that mutations affecting CARD-containing proteins are described in patients with psoriasis, pityriasis rubra pilaris, atopic dermatitis, and fungal infections. The review suggests these mutations may have therapeutic implications but states explicitly that more information is needed. No clinical data, response rates, or survival figures are provided.
What is still missing: no clinical trial has tested a drug targeting these genetic or environmental pathways in dermatitis patients. The genetic associations from the 2016 study require replication in larger, more diverse cohorts. The CARD mutation findings are preliminary and lack any linked treatment data. Funding for adequately powered trials that stratify patients by genetic or microbial profiles is 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.
Exogenous factors in the pathogenesis of atopic dermatitis: Irritants and cutaneous infections
AbstractAtopic dermatitis (AD) is a chronic relapsing inflammatory cutaneous disease that is often associated with other atopic symptoms, such as food allergy, allergic rhinitis and asthma, leading to significant morbidity and healthcare costs. The pathogenesis of AD is complicated and multifactorial. Although the aetiology of AD remains incompletely understood, recent studies have provided further insight into AD pathophysiology, demonstrating that the interaction among genetic predisposition, immune dysfunction and environmental provocation factors contributes to its development. However, the increasing prevalence of AD suggests that environmental factors such as irritation and cutaneous infection play a crucial role in triggering and/or aggravating the disease. Of note, AD skin is susceptible to bacterial, fungal and viral infections, and microorganisms may colonize the skin and aggravate AD symptoms. Overall, understanding the mechanisms by which these risk factors affect the cutaneous immunity of patients with AD is of great importance for developing a precision medicine approach for treatment. This review summarizes recent developments in exogenous factors involved in the pathogenesis of AD, with special emphasis on irritants and microbial infections.
Journal of Occupational and Environmental Medicine · 2016 · 14 citations
Genetic Basis of Irritant Susceptibility in Health Care Workers
AbstractOBJECTIVE: The aim of this study was to investigate the association of single nucleotide polymorphisms (SNPs) within genes involved in inflammation, skin barrier integrity, signaling/pattern recognition, and antioxidant defense with irritant susceptibility in a group of health care workers. METHODS: The 536 volunteer subjects were genotyped for selected SNPs and patch tested with three model irritants: sodium lauryl sulfate (SLS), sodium hydroxide (NaOH), and benzalkonium chloride (BKC). Genotyping was performed on genomic DNA using Illumina Goldengate custom panels. RESULTS: The ACACB (rs2268387, rs16934132, rs2284685), NTRK2 (rs10868231), NTRK3 (rs1347424), IL22 (rs1179251), PLAU (rs2227564), EGFR (rs6593202), and FGF2 (rs308439) SNPs showed an association with skin response to tested irritants in different genetic models (all at P < 0.001). Functional annotations identified two SNPs in PLAU (rs2227564) and ACACB (rs2284685) genes with a potential impact on gene regulation. In addition, EGF (rs10029654), EGFR (rs12718939), CXCL12 (rs197452), and VCAM1 (rs3917018) genes showed an association with hand dermatitis (P < 0.005). CONCLUSIONS: The results demonstrate that genetic variations in genes related to inflammation and skin homeostasis can influence responses to irritants and may explain inter-individual variation in the development of subsequent contact dermatitis.
Journal of Skin and Sexually Transmitted Diseases · 2022 · 0 citations · open access
Caspase recruitment domain-containing proteins and dermatoses
AbstractThe caspase recruitment domain (CARD) is a protein interaction module that comes under the death domain superfamily. CARD mediates important cellular signaling events. Abnormalities in these cellular signaling events play a role in the pathogenesis of malignancies and immune disorders. The significance of CARD in dermatological diseases is less discussed. Mutations affecting CARD-containing proteins are reported to play a pathogenic role in certain patients with dermatoses such as psoriasis, pityriasis rubra pilaris, atopic dermatitis, and fungal infections. These underlying mutations are suggested to have therapeutic implications in various dermatoses, though more information is needed regarding this. This review discusses the association between dermatoses and mutations involving CARD-containing proteins.
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.
