DeCure's autonomous Dermatology AI scientist is researching a drug-repurposing hypothesis for psoriasis — screening already-approved drugs against its 43-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePsoriasis maps to a 43-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
approvedIsotretinoinApproved drugapprovedAlitretinoinRetinoid receptor agonistapprovedAcitretinApproved drug
Structures already discussed alongside psoriasis in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
THE 2.1 ANGSTROM RESOLUTION CRYSTAL STRUCTURE OF THE HETERODIMER OF THE HUMAN RXRALPHA AND PPARGAMMA LIGAND BINDING DOMAINS RESPECTIVELY BOUND — Alitretinoin has a real, experimentally solved structure in complex with this target (PDB 1FM6, 2.1 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet 9crdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1FM6 · 2.1 Å · ligand Alitretinoin (9CR). Experimental structure, not a prediction.
What the evidence adds up to
Acitretin is an oral retinoid approved for psoriasis that is not immunosuppressive, making it an option for patients with HIV, hepatitis B, hepatitis C, or malignancy who cannot take immunosuppressants. It is a treatment of choice for pustular psoriasis. As monotherapy for chronic plaque psoriasis, acitretin is less effective, but combination with UVB or psoralen plus UVA phototherapy can enhance efficacy. At low doses it is generally well tolerated for long-term use.
In a 1985 comparison of 29 patients with chronic plaque psoriasis, isotretinoin was less effective than etretinate. In 11 patients with generalised pustular psoriasis, isotretinoin controlled pustulation and systemic symptoms in ten cases, but additional therapy was needed for complete clearing of all lesions.
A 2012 open-label study treated seven patients with recalcitrant palmoplantar pustular psoriasis using oral alitretinoin 30 mg once daily for 12 weeks. The palmoplantar pustular psoriasis area and severity index and visual analogue scales for pruritus and pain decreased significantly. Patient-assessed clinical improvement ranged from 60% to 90%. Skin biopsies showed a significant reduction in neutrophils, macrophages, and dendritic cells. Two patients reported headache during the first month. The study had no control group and allowed concomitant topical therapy.
A 2009 gene expression analysis of peripheral blood mononuclear cells from five psoriasis patients and eight controls identified 212 differentially expressed genes, with 63 induced (including CD44, CD56, IL7R) and 139 reduced (including sphingosine kinase 1 and p16-INK). The authors speculated these genes may be involved in the pathogenesis of psoriasis and could represent novel drug targets. A 2024 review notes that despite available therapies, unmet needs remain for moderate and severe psoriasis, and that ongoing development of innovative therapies aims to provide effective and safe options for unresponsive disease. What is still missing are controlled trials for alitretinoin in palmoplantar disease, larger and stratified patient populations to confirm the gene expression findings, and a clearer understanding of which patients will benefit from which retinoid.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Expert Opinion on Drug Safety · 2009 · 70 citations
A review of acitretin for the treatment of psoriasis
AbstractBACKGROUND: Acitretin is an oral retinoid that is approved for the treatment of psoriasis. It is unique compared to other systemic therapies for psoriasis such as methotrexate and cyclosporine in that it is not immunosuppressive. It is, therefore, safe for use in psoriasis patients with a history of chronic infection such as HIV, hepatitis B, hepatitis C or malignancy who have a contraindication to systemic immunosuppressive therapy and require systemic therapy because topical therapy is inadequate and they are unable to commit to phototherapy. Acitretin is one of the treatments of choice for pustular psoriasis. Even though acitretin is less effective as a monotherapy for chronic plaque psoriasis, combination therapy with other agents, especially UVB or psoralen plus UVA phototherapy, can enhance efficacy. OBJECTIVE: To provide an updated review of the safety and efficacy of acitretin in the treatment for psoriasis. METHODS: Literature review of journal articles from 2008 to 2009 since the last review of acitretin evaluated medical literature from 2005 to 2008. RESULTS/CONCLUSION: Acitretin is an effective systemic therapy for psoriasis and is generally well tolerated at low doses for long-term use. If monotherapy with acitretin is inadequate, it can be used in combination with other treatments, particularly UVB phototherapy, to increase efficacy.
Isotretinoin vs Etretinate Therapy in Generalized Pustular and Chronic Psoriasis
AbstractThe clinical response to isotretinoin (13-cis-retinoic acid) in 11 patients with generalized pustular psoriasis was evaluated. Control of pustulation and systemic symptoms was achieved in ten cases, but additional therapy was required to produce complete clearing of all psoriatic lesions. Also, the efficacy of isotretinoin and etretinate in the treatment of chronic plaque psoriasis was compared in 29 patients. Isotretinoin was found to be less effective than etretinate in the treatment of chronic plaque psoriasis.
British Journal of Dermatology · 2012 · 35 citations
Alitretinoin abrogates innate inflammation in palmoplantar pustular psoriasis
AbstractBACKGROUND: Palmoplantar pustular psoriasis is often recalcitrant to therapy. Here we evaluated the therapeutic effect of alitretinoin in patients with recalcitrant palmoplantar pustular psoriasis and investigated subsequent immunopathological alterations. METHODS: Seven patients with palmoplantar pustular psoriasis were treated with oral alitretinoin 30 mg once daily for 12 weeks. Efficacy was assessed by palmoplantar pustular psoriasis area and severity index (PPPASI), visual analogue scales (VAS) on intensity of pain and pruritus and an overall patient assessment. Immunohistochemical staining for neutrophil elastase, CD3, CD4, CD8, CD1a CD11c, CD303,CD68, CD69, CD208 and HLA-DR was on lesional skin biopsies obtained before and after 12 weeks of treatment. RESULTS: PPPASI and VAS for pruritus and pain decreased significantly after 12 weeks of treatment with alitretinoin. The overall patient assessment ranged from 60% to 90% clinical improvement. In correlation with clinical improvement a significant reduction, particularly of neutrophils, macrophages and dendritic cells, was also observed in the skin sections. Alitretinoin was well tolerated except for headache during the first month of treatment in two patients. Limitations of the study are a missing control group and the concomitant usage of topical therapy. DISCUSSION: Our findings suggest that alitretinoin may represent a new and promising therapy for recalcitrant palmo-plantar psoriasis and warrants further controlled studies to confirm efficacy and safety of alitretinoin in this disease.
Annals of Dermatology · 2009 · 21 citations · open access
A Global Gene Expression Analysis of the Peripheral Blood Mononuclear Cells Reveals the Gene Expression Signature in Psoriasis
AbstractBACKGROUND: Psoriasis is a chronic inflammatory skin disease that affects approximately 1~3% of the general population. OBJECTIVE: We performed cDNA microarray analysis with using the dendrimer labelling method to investigate the gene expression profile in the peripheral blood mononuclear cells (PBMCs) of psoriatic patients. METHODS: The peripheral blood mononuclear cells of 5 patients with psoriasis and 8 control subjects were used in the gene expression analyses of psoriasis. RESULTS: We identified 212 differentially expressed genes that showed at least a two-fold induction and/or reduction in psoriatic patients. Among those, 63 genes, including CD44, CD56 and IL7R, were induced, while 139 genes, including the sphingosine kinase 1 and p16-INK genes, were reduced in the psoriatic patients. CONCLUSION: We can speculate that these genes may have a role for the pathogenesis of psoriasis via their affecting different cellular functions. Our results suggest a possible mechanism by which activated immune cells migrate from the blood to the skin in psoriatic patients, and we provide novel putative targets for developing drugs to treat psoriasis.
Expert Opinion on Pharmacotherapy · 2024 · 8 citations
Novel pharmacotherapies and breakthroughs in psoriasis treatment: 2024 and beyond
AbstractINTRODUCTION: The use of the current available therapies for psoriasis management may sometimes be limited by reduced patients' compliance, safety issues for patients' comorbidities, primary lack of efficacy, loss of effectiveness, development of side effects. In this context, several clinical trials investigating the use of both topical and systemic therapies are ongoing, and other new drugs will be approved soon. AREAS COVERED: The aim of this manuscript is to review current literature and to provide an overview of the current and future trends in psoriasis treatment. A comprehensive review of the English-language medical literature was performed using Pubmed and clinicaltrials.gov databases. EXPERT OPINION: Although several therapies are currently available for psoriasis' treatment, unmet needs still exist for patients with moderate and severe psoriasis and hence expanding the therapeutic armamentarium is desirable for a more personalized approach. The ongoing development of innovative therapies could provide effective and safe therapies in the future enhancing the therapeutic management of moderate-severe unresponsive psoriasis.
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.
