DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for tuberous sclerosis — screening already-approved drugs against its 20-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleTuberous sclerosis maps to a 20-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
approvedEverolimusApproved drugapprovedSirolimusApproved drug
Structures already discussed alongside tuberous sclerosis in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
ATOMIC STRUCTURE OF THE RAPAMYCIN HUMAN IMMUNOPHILIN FKBP-12 COMPLEX — Sirolimus has a real, experimentally solved structure in complex with this target (PDB 1FKB, 1.7 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.
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helix sheet rapdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1FKB · 1.7 Å · ligand Sirolimus (RAP). Experimental structure, not a prediction.
What the evidence adds up to
In a 2016 prospective single-blinded crossover study, twelve patients with tuberous sclerosis complex applied topical 0.1% sirolimus (made by crushing tablets into petrolatum) to one side of the face and plain vaseline to the other. The treated side showed significant improvement in redness and extension of angiofibromas measured by a facial angiofibroma severity index. Three patients reported itching and irritation, managed with topical hydrocortisone. The authors noted that efficacy diminished with time but that repetitive use remained effective.
A 2021 systematic review pooled thirty studies (four randomised trials, seventeen case series, nine single case reports) covering 508 patients treated over twenty years. Topical rapamycin (sirolimus) concentrations ranged from 0.003% to 1% in gel, ointment and solution formulations. The review stated that rapamycin demonstrated effectiveness in all included studies except for five patients in one phase 1b study, and that it was safe for facial angiofibromas. The authors concluded it can be considered an effective and safe option but called for further long-term studies to establish an evidence-based protocol.
A 2022 case report described a young woman whose facial angiofibroma led to a diagnosis of tuberous sclerosis complex with multiple system involvement, including a large renal angiomyolipoma pressing on the liver. She had no subjective symptoms. After multidisciplinary consultation she was treated with oral everolimus and followed regularly. The report emphasised that dermatologists should look for systemic involvement and that multidisciplinary lifelong management is key.
What remains missing are long-term randomised controlled trials comparing different concentrations and formulations of topical sirolimus, standardised outcome measures, and data on whether topical treatment alters the natural history of angiofibromas or prevents progression. No trial has yet established an optimal dosing schedule or duration of therapy. The evidence base is limited by small sample sizes, short follow-up, and lack of blinding in most studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Indian Journal of Dermatology Venereology and Leprology · 2016 · 23 citations · open access
Topical sirolimus for the treatment of angiofibromas in tuberous sclerosis
AbstractBACKGROUND: The skin is one of the most affected organs in tuberous sclerosis complex and angiofibromas are seen in almost 80% of such patients. These benign tumors impose a great psycho-social burden on patients. OBJECTIVE: The aim of the study was to evaluate the effectiveness and tolerability of topical sirolimus for facial angiofibromas in patients with tuberous sclerosis complex. METHODS: This was a prospective, single-blinded, cross-over study which involved twelve patients. We investigated the effect and safety of topical 0.1% sirolimus, which was obtained by crushing sirolimus tablets and mixing it with petrolatum. The patients were asked to apply the cream to one side of their face, and vaseline to the other side. The effect of topical sirolimus was evaluated using the "facial angiofibroma severity index." RESULTS: There was a significant improvement in the redness and extension of the tumors on the sides to which the active ingredient was applied. Some side effects such as itching and irritation occurred in three patients, which were treated with topical hydrocortisone cream. CONCLUSION: Topical sirolimus appears to be a promising, fairly well tolerated treatment for facial angiofibromas in patients with tuberous sclerosis complex. Although its efficacy diminishes with time, repetitive usage is effective.
Journal of Dermatological Treatment · 2021 · 14 citations
Topical rapamycin in the treatment of facial angiofibromas in tuberous sclerosis: a systematic review based on evidence
AbstractINTRODUCTION: facial angiofibromas of tuberous sclerosis are the most prevalent cutaneous manifestation, affecting 80% of patients, which cause facial lesions with negative psychosocial consequences. Newly, topical rapamycin has been established as an effective and safe therapy for this skin condition. PURPOSE: to analyze the available scientific evidence about the effectiveness and safety of topical sirolimus in the treatment of facial angiofibromas in tuberous sclerosis. METHODS: a literature search was conducted in PubMed and Cochrane. Effectiveness and safety were analyzed along with the main characteristics of each formulation in all included studies. RESULTS: thirty studies were included involving a total of 508 patients, developed in the last 20 years. Four randomized clinical trial, 17 case series and 9 single case reports were founded. Multiple topical rapamycin concentrations (0.003-1%) and formulations (gel, ointment, solution) were found in literature. Rapamycin demonstrated its effectiveness in all studies included, except for 5 patients in a 1 b study. Rapamycin was shown to be safe for the treatment of FA. CONCLUSIONS: Topical sirolimus can be considered an effective and safety option for the treatment of facial angiofibromas in tuberous sclerosis. However, further long-term studies need to establish an evidence-based therapeutic protocol.KEY MESSAGEUpdated review to date in topical rapamycin for facial angiofibromas, allowing support in therapeutic decisions.
Tuberous sclerosis complex with skin lesions as the initial presentation: A case report and multidisciplinary discussion.
AbstractWe reported a case of tuberous sclerosis complex with facial angiofibroma as the initial presentation and conducted a multidisciplinary discussion. The patient, a young female, was admitted to the Department of Dermatology for cosmetic purpose. After the examination, she was found to have multiple system involvement, including a large renal angiomyolipoma pressing on the liver. She never had any subjective symptom. After consultation by the multidisciplinary team of tuberous sclerosis complex, the patient was treated with everolimus orally and followed up regularly. It is suggested that dermatologists should pay attention to the systemic involvement of patients with tuberous sclerosis complex. Early intervention can prolong the life of patients and improve their life quality. Multidisciplinary collaboration for lifelong disease management is the key to enhance the diagnosis and treatment for tuberous sclerosis complex and enhance the prognosis of patients.
Disease module: DeepOracle (Open Targets). Approved indication: ChEMBL drug_indication (max_phase=4). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works, 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.
