DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for colitis — screening already-approved drugs against its 38-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleColitis maps to a 38-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 colitis 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
dihydrolipoamide dehydrogenase (DLD) — DLD 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 faddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6I4R · 1.439 Å · ligand FLAVIN-ADENINE DINUCLEOTIDE (FAD). Experimental structure, not a prediction.
What the evidence adds up to
A 2023 systematic review of 56 real-world studies found that dose escalation and treatment switching are common in moderate-to-seevere ulcerative colitis treated with infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, or tofacitinib. After dose escalation, clinical response rates ranged from 20% to 95% over 1.8 to 36 months, and clinical remission rates from 10% to 94% over the same period. Colectomy rates after dose escalation were 0% to 33% over 12 to 38 months, and adverse event rates were 0% to 18%. Treatment switching occurred in 4% to 70% of patients over 3 to 62 months; up to 35% of patients underwent colectomy 12 to 120 weeks after switching, and 13% to 38% experienced adverse events. The review noted that a proportion of patients fail to achieve optimal clinical and economic outcomes with these strategies.
A 2009 review argued that early aggressive top-down therapy with infliximab induces rapid clinical response, enhances quality of life, promotes mucosal healing, and reduces surgeries and indirect costs in severe extensive ulcerative colitis. It stated that long-term infliximab treatment is safe and well tolerated, and suggested this approach may be more effective in a subgroup of patients. A 1965 paper described medical treatment including diet, sedatives, antidiarrheal agents, antibiotics, chemotherapy, and steroids, stressing individualised treatment and teamwork, but noted the handicap of dealing with a disease of unknown cause.
A 2020 Spanish case series reported two patients with ulcerative colitis refractory to conventional and biological therapy who responded successfully to tofacitinib, an oral small molecule JAK/STAT inhibitor. The authors stated that tofacitinib is safe and effective in inducing and maintaining remission in moderate-severe UC, but this claim is based on two cases.
What is still missing is prospective, randomised evidence comparing early aggressive strategies to standard step-up care in defined patient subgroups, and larger controlled trials of tofacitinib versus other agents after prior biologic failure. The 2023 review also noted that economic data were limited to tumour necrosis factor inhibitors, and that clinical response and remission rates varied widely across studies, with no single strategy consistently outperforming others.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
ClinicoEconomics and Outcomes Research · 2023 · 15 citations · open access
Systematic Literature Review of Real-World Evidence on Dose Escalation and Treatment Switching in Ulcerative Colitis
AbstractBackground: Currently approved biologic therapies for moderate-to-severe ulcerative colitis have well-established efficacy. However, many patients fail to respond or lose response, leading to dose escalation or treatment switching. Objective: We sought to identify real-world evidence on dose escalation and treatment switching and associated clinical and economic outcomes among adults with ulcerative colitis treated with infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, or tofacitinib. Methods: We conducted a systematic search of Embase, MEDLINE (up to 26 August 2020), and conference proceedings (2017-2020) for studies in adults with ulcerative colitis to assess clinical response and remission, colectomy, adverse events, and economic outcomes related to dose escalation and treatment switching. Results: In 56 studies, dose escalation and treatment switching involving infliximab and/or adalimumab were most frequently investigated. Rates of clinical response after dose escalation were 20-95% (1.8-36 months), clinical remission rates were 10-94% (1.8-36 months), colectomy rates were 0-33% (12-38 months), and adverse event rates were 0-18%. Treatment switching rates in 21 studies were 4-70% over 3-62 months, with switch due to loss of response rates of 4-35% over 12-62 months (7 studies). Up to 35% of patients underwent colectomy 12-120 weeks after switching, and 13-38% experienced adverse events. Data relating to economic outcomes were limited to tumor necrosis factor inhibitors, but demonstrated increased direct costs associated with both dose escalation and treatment switching. Conclusion: Dose escalation and treatment switching are common with existing therapies. However, clinical response and remission rates vary, and a proportion of patients fail to achieve optimal clinical and economic outcomes. This highlights the need for more efficacious and durable treatments for patients with moderate-to-severe ulcerative colitis.
World Journal of Gastroenterology · 2009 · 1 citations · open access
Early aggressive therapy for severe extensive ulcerative colitis
AbstractThe current ulcerative colitis (UC) treatment algorithm involves a step-up therapeutic strategy, mainly aiming at inducing and maintaining its clinical remission. Although this therapeutic strategy may seem to be cost-efficient and reduce the risk of side effects, recent trials and case reports have shown that top-down therapy using infliximab induces a rapid clinical response, enhances patient quality of life, promotes mucosal healing, reduces surgeries and indirect cost of treatment for patients with severe UC. Moreover, since long-term treatment with infliximab is safe and well tolerated, early aggressive top-down therapeutic strategy may be a more effective approach, at least in a subgroup of severe extensive UC patients.
AbstractMedical treatment for ulcerative colitis includes diet, sedatives, antidiarrheal agents, antibiotics, chemotherapy and steroids. Their application in cases of varying severity is outlined. Several complications are discussed briefly. Individualized treatment and teamwork by internist, surgeon and psychiatrist are stressed. Despite the handicap of dealing with a disease of unknown cause, recent advances in both medical and surgical skills permit a degree of optimism.
Revista médica de Chile · 2020 · 0 citations · open access
Tofacitinib en el tratamiento de la colitis ulcerosa: casos clínicos
AbstractBiological therapy dramatically changed the management of Ulcerative Colitis (UC). However, a significant number of these patients fail to respond or have secondary loss of response to this strategy. In this clinical situation, the options include intensification of anti-TNF therapy, the use of a second anti-TNF or being switched to another drug class. Among the later, tofacitinib, an oral small molecule directed against the JAK/STAT pathway, is safe and effective in inducing and maintaining remission in patients with moderate-severe UC. We report two patients with UC refractory to conventional treatment and biological therapy, who responded successfully to the use of tofacitinib.
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.
