DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for drug-induced lupus erythematosus — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDrug-induced lupus erythematosus maps to a 1-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 drug-induced lupus erythematosus 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
malic enzyme 1 (ME1) — ME1 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 ndpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7X11 · 2.07 Å · ligand NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (NDP). Experimental structure, not a prediction.
What the evidence adds up to
Drug-induced lupus is a disorder similar to idiopathic systemic lupus erythematosus in its manifestations, but the two entities have significant serologic and clinical differences that call into question whether they represent an identical disease process. The condition is defined as a lupic syndrome secondary to continuous exposure to a drug, which induces auto-immunity phenomena. Its mechanism remains unclear, involving genetic and environmental factors. The clinical, biological and histological aspects are similar to those of systemic lupus erythematosus, but the lower severity of symptoms, the rarity of systemic attacks, and the regression of signs when the inducing drug is stopped favour the diagnosis of drug-induced lupus. Treatment involves interruption of the drug in question, with a favourable evolution often after the causative drug has been stopped.
Many drugs have been reported to induce autoantibodies, but only a few have a definitive association with drug-induced autoimmune disease. The prototype drug for drug-induced lupus is minocycline. The production of autoantibodies and induction of symptoms results from a variety of mechanisms, which can include suppression of central or peripheral tolerance, alteration of gene transcription in T and B cells, abnormal cytokine and/or cytokine receptor balance and function, chromatin structure modification, and antigen modification. Multiple mechanisms may apply for different drugs; for example, DNA hypomethylation may occur with hydralazine, leading to increased transcription, increased LFA-1, generation of autoreactive T cells, and a breakdown in peripheral tolerance. Most patients with newly formed autoantibodies resulting from drugs do not develop clinical disease.
In lupus nephritis, many synthetic immunosuppressive drugs have a low therapeutic index. Good knowledge of their pharmacologic characteristics, mechanisms of action, and drug-to-drug interactions, coupled with a strategy to increase immunosuppression in active phases of systemic lupus erythematosus while reducing dosage in quiescent periods, can reduce iatrogenic morbidity while maintaining efficacy. Biologic agents may allow reduction in the use or dosage of synthetic immunosuppressive drugs. The explosion in the use of biological modifiers has been associated with production of autoantibodies, illustrating the complex nature of these interactions, in that these agents are frequently used to treat autoimmunity yet may produce autoimmune diseases themselves.
What is still missing is a clear understanding of the mechanisms that determine why only a subset of patients exposed to a given drug develop clinical disease, and why most patients with drug-induced autoantibodies remain asymptomatic. No randomised controlled trials have established optimal strategies for tapering or withdrawing the offending drug, nor for managing cases where symptoms do not resolve promptly. Patient stratification by genetic or environmental risk factors remains absent from clinical practice, and funding for such mechanistic and trial-based work is lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Postgraduate Medicine · 1996 · 34 citations
Drug-induced lupus
AbstractMore than 70 medications have been implicated as a cause of drug-induced lupus. The condition most commonly manifests with arthralgias and fever. The most important laboratory feature is an elevated antinuclear antibody titer, which often corresponds to the presence of antihistone antibodies. Fortunately, the course of drug-induced lupus is more benign than that of idiopathic systemic lupus erythematosus. Clinical resolution generally occurs after withdrawal of the offending agent. The patient described here exemplifies the importance of maintaining a heightened awareness of this uncommon disorder. For him, delayed diagnosis of drug-induced lupus resulted in prolonged discomfort, restriction of daily activities, and unnecessary therapeutic intervention.
AbstractDrug-induced lupus is a disorder similar to idiopathic systemic lupus erythematosus in terms of manifestations. However, these entities have significant serologic and clinical differences, which call into question the concept that they represent an identical disease process. Nonetheless, further research into the drug-induced disease will enhance our understanding and management of this clinically significant iatrogenic disease and will likely contribute to our comprehension of the pathogenesis of autoimmunity.
Expert Review of Clinical Pharmacology · 2019 · 31 citations
Cutaneous lupus erythematosus induced by drugs - novel insights
AbstractIntroduction: There is a growing list of drugs implicated in inducing both subacute and chronic forms of cutaneous lupus erythematosus. It is important to recognize these drugs in order to quickly treat patients with drug induced disease.Areas covered: This paper reviews the current literature describing drugs implicated in causing cutaneous lupus erythematosus. A Pubmed search was used to compile a list of medications implicated up to August 2019. It reviews new classes of drugs identified as causing cutaneous lupus erythematosus, the pathophysiology of the disease process, and current recommendations for treatment of the disease.Expert opinion: Many drugs have been identified as inducing lupus, and many more continue to be described in new reports. Further research is needed to understand this phenomenon, which will aid in the diagnosis and treatment of affected patients.
Indian Journal of Medical Sciences · 2005 · 23 citations
Mycophenolate mofetil in neuropsychiatric systemic lupus erythematosus
AbstractNeuropsychiatric abnormalities frequently occur in patients with systemic lupus erythematosus, affecting as many as 14-75% of people with this disease. High-dose steroid with or without anticoagulation is the mainstay of treatment in neuropsychiatric systemic lupus erythematosus (NPSLE). Use of mycophenolate as a steroid sparing drug may be a potential alternative agent in the therapy of NPLE, but lack of randomized trials and cost prohibit its widespread use. Its safety profile is higher than that of cyclophosphamide and azathioprine. We report a successfully treated case of neuropsychiatric systemic lupus erythematosus, presenting as psychosis, whose long-term remission was maintained on treatment with mycophenolate mofetil.
Expert Opinion on Pharmacotherapy · 2017 · 6 citations
Synthetic pharmacotherapy for lupus nephritis
AbstractINTRODUCTION: Lupus nephritis is a frequent complication and a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Area covered: The main characteristics and mechanisms of action of the synthetic drugs more frequently used in lupus nephritis are described. Possible strategies aimed to reduce the potential adverse events without affecting efficacy are reported. Expert opinion: Many synthetic immunosuppressive drugs used in lupus nephritis have a low therapeutic index. Good knowledge of their pharmacologic characteristics, mechanisms of action, and drug-to-drug interactions, coupled with a strategy aimed to increase immunosuppression in the active phases of SLE while reducing the dosage in quiescent periods can reduce the iatrogenic morbidity while maintaining efficacy. Biologic agent may allow to reduce the use or the dosage of synthetic immunosuppressive drugs.
AbstractThe subacute cutaneous lupus erythematosus (SCLE) is a distinct subtype of lupus erythematosus (LE) representing specific clinical and serological features. Almost 20%-30% of the cases with SCLE are predicted to associated with medications. Thiazide diuretics, terbinafine, antiepileptic, and proton pump inhibitors are the best-known drugs to induce drug-related SCLE. Herein we want to present a 65-year-old female with alendronate induced SCLE, resistant to classical therapies, and respond well to intravenous immunoglobulin (IVIG), suggesting that IVIG could be an alternative treatment in patients resistant to classical treatment protocols.
Société Marocaine de Rhumatologie · 2021 · 0 citations · open access
Induced lupus : paradigm and particularities
AbstractInduced lupus (IL) is defined as a lupic syndrome secondary to continuous exposure to a drug, which is responsible for the induction of auto-immunity phenomena. Its mechanism remains unclear, involving several factors, in particular genetic and environmental factors. The clinical, biological and histological aspects are similar to those of systemic lupus erythematosus (SLE). The lower severity of symptoms, the rarity of systemic attacks and the regression of signs when the inducing drug is stopped are in favor of IL. The treatment of IL involves the interruption of the drug in question, with a favorable evolution often after the causative drug has been stopped.
Journal of Autoimmunity · 2009 · 0 citations · open access
コイル塞栓術を施行したAnterior Condylar Confluence 硬膜動静脈瘻の一例
AbstractDrug-induced autoimmunity is an idiosyncratic, non-IgE immune related drug reaction. Interestingly, although many drugs have been reported to induce autoantibodies, only a few have a definitive association with drug-induced autoimmune disease. The prototype disease is drug-induced lupus and the typical drug for drug-induced lupus is minocycline. The production of autoantibodies and the induction of symptoms in drug-induced lupus results from a variety of mechanisms, which can include suppression of central or peripheral tolerance, alteration of gene transcription in T and B cells, abnormal cytokine and/or cytokine receptor balance and function, chromatin structure modification and antigen modification. Multiple mechanisms may apply for different drugs, and understanding the pharmacological actions of these agents helps us decipher the etiology. For example, DNA hypomethylation may occur with hydralazine, which leads to increased transcription, increased LFA-1, the generation of autoreactive T cells and a breakdown in peripheral tolerance. Frequently, more than one pathway may be involved. Interestingly, most patients with newly formed autoantibodies resulting from drugs do not develop clinical disease. Nonetheless, the explosion in the use of biological modifiers has been associated with production of autoantibodies, an observation that illustrates the complex nature of these interactions, in that these agents are frequently used to treat autoimmunity, yet may produce autoimmune diseases themselves.
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.
