DeCure's autonomous AMR AI scientist is researching a drug-repurposing hypothesis for bacterial disease — screening already-approved drugs against its 41-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBacterial disease maps to a 41-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
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Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Structures already discussed alongside bacterial disease in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
TetR(D) — Minocycline has a real, experimentally solved structure in complex with this target (PDB 2XPV, 1.49 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 miydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2XPV · 1.49 Å · ligand Minocycline (MIY). Experimental structure, not a prediction.
What the evidence adds up to
Minocycline, a broad-spectrum antibiotic, has been studied for neurodegenerative and psychiatric diseases due to its anti-inflammatory properties. A review covering 74 preclinical studies and 44 clinical trials from 1995 to 2020 found that while minocycline mostly proved effective in animal models, clinical results showed divergent outcomes, with positive results in some studies counterbalanced by a number of cases with no significant improvements. The review authors concluded that discrepancies between preclinical and clinical data indicate caution is needed.
In a 2019 hollow-fibre system model of pulmonary Mycobacterium avium complex disease, minocycline achieved a microbial kill of 3.6 log10 cfu/mL below stasis. Monte Carlo experiments identified that a clinical dose of 200 mg/day achieved a bactericidal effect exposure target in approximately 50% of patients, while 400 mg/day achieved this in 73.6% of patients. The authors proposed a clinical trial for validation. However, a separate 2019 study using time-kill experiments with four strains of Acinetobacter baumannii found that minocycline's antimicrobial activity was dramatically reduced in the presence of serum compared to standard broth, and the authors suggested that dose escalation might not be the best approach to improve clinical efficacy for bacteraemia.
A 2025 case report described a patient with severe pneumonia caused by Chlamydia psittaci and a multi-drug-resistant bacterial infection who failed initial treatment with moxifloxacin and doxycycline. After switching to omadacycline, a novel aminomethylcycline antibiotic, for 48 hours, all complications were rapidly alleviated and the patient was successfully treated. A 2008 multicentre study from Argentina tested tigecycline, another tetracycline-class antibiotic, against 3,182 clinical isolates and found 100% susceptibility for all Gram-positive bacteria tested, including methicillin-resistant staphylococci and vancomycin-resistant enterococci, and susceptibility ranging from 88 to 100% for Enterobacteriaceae, with 92% of Acinetobacter isolates susceptible.
What is still missing are large, well-controlled clinical trials for minocycline in specific bacterial infections, particularly those caused by multi-drug-resistant organisms, and a clearer understanding of how serum protein binding affects its efficacy in patients. The proposed trial for minocycline at 400 mg/day in pulmonary MAC disease has not been reported as completed. For omadacycline and tigecycline, more data from randomised controlled trials in defined patient populations are needed, and the problem of patient stratification by pathogen susceptibility and infection site remains unresolved.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
European Journal of Neurology · 2020 · 92 citations · open access
Minocycline in neurodegenerative and psychiatric diseases: An update
AbstractBACKGROUND AND PURPOSE: Minocycline is a broad-spectrum antibiotic, effective as a chronic treatment for recurrent bacterial infections. Beyond its antibiotic action, minocycline also has important anti-inflammatory, antioxidant and antiapoptotic properties. Its efficacy has therefore been evaluated in many neurodegenerative and psychiatric diseases that have an inflammatory basis. Our aim was to review preclinical and clinical studies performed in neurological and psychiatric diseases whose treatment involved the use of minocycline and thereby to discern the possible beneficial effect of minocycline in these disorders. METHODS: Completed and ongoing preclinical studies and clinical trials of minocycline for both neurodegenerative diseases and psychiatric disorders, published from January 1995 to January 2020, were identified through searching relevant databases (https://www.ncbi.nlm.nih.gov/pubmed/, https://clinicaltrials.gov/). A total of 74 preclinical studies and 44 clinical trials and open-label studies were selected. RESULTS: The results of the nearly 20 years of research identified are diverse. While minocycline mostly proved to be effective in animal models, clinical results showed divergent outcomes, with positive results in some studies counterbalanced by a number of cases with no significant improvements. Specific data for each disease are further individually described in this review. CONCLUSIONS: Despite minocycline demonstrating antioxidant and anti-inflammatory effects, discrepancies between preclinical and clinical data indicate that we should be cautious in analyzing the outcomes. Improving and standardizing protocols and refining animal models could help us to determine if minocycline really is a useful drug in the treatment of these pathologies.
Infection and Drug Resistance · 2025 · 64 citations · open access
Effectiveness of Omadacycline in a Patient with Chlamydia psittaci and KPC-Producing Gram-Negative Bacteria Infection
AbstractAbstract: Chlamydia psittaci is one of the primary pathogens responsible for community-acquired atypical pneumonia. If not treated promptly, it can progress to severe pneumonia and may lead to multiple organ dysfunction as well as secondary infections with multi-drug-resistant (MDR) bacteria. Omadacycline, a novel aminomethylcycline antibiotic derived from tetracycline, exhibits high activity against various bacterial strains. This case report describes a patient who developed severe pneumonia caused by Chlamydia psittaci in conjunction with a MDR bacterial infection. Despite initial treatment with moxifloxacin and doxycycline, the patient experienced treatment failure. The patient’s condition deteriorated, presenting complications such as progressive infection, leukopenia, liver dysfunction, electrolyte imbalances, and respiratory alkalosis. Following the adjustment to omadacycline therapy for 48 hours, all complications were rapidly alleviated, leading to successful treatment of the patient. Keywords: omadacycline, Chlamydia psittaci , multiple drug resistance, Kleber pneumoniae, Acinetobacter baumannii
Journal of Antimicrobial Chemotherapy · 2019 · 26 citations · open access
Minocycline treatment for pulmonary Mycobacterium avium complex disease based on pharmacokinetics/pharmacodynamics and Bayesian framework mathematical models
AbstractOBJECTIVES: Our aim was to identify the pharmacokinetic/pharmacodynamic parameters of minocycline in the hollow-fibre system (HFS) model of pulmonary Mycobacterium avium complex (MAC) and to identify the optimal clinical dose. METHODS: Minocycline MICs for 55 MAC clinical isolates from the Netherlands were determined. We also co-incubated primary isolated macrophages infected with MAC with minocycline. Next, we performed a 28 day HFS-MAC model dose-response study in which we mimicked pulmonary concentration-time profiles achieved in patients. The HFS-MAC model was sampled at intervals to determine the minocycline pharmacokinetics and MAC burden. We identified the AUC0-24/MIC ratios associated with 1.0 log10 cfu/mL kill below day 0 (stasis), defined as a bactericidal effect. We then performed 10000 Monte Carlo experiments to identify the optimal dose for a bactericidal effect in patients. RESULTS: The MIC for 50% and 90% of cumulative clinical isolates was 8 and 64 mg/L, respectively. Minocycline decreased MAC bacterial burden below stasis in primary isolated macrophages. In the HFS-MAC model, minocycline achieved a microbial kill of 3.6 log10 cfu/mL below stasis. The AUC0-24/MIC exposure associated with a bactericidal effect was 59. Monte Carlo experiments identified a minocycline susceptibility MIC breakpoint of 16 mg/L. At this proposed breakpoint, the clinical dose of 200 mg/day achieved the bactericidal effect exposure target in ∼50% of patients, while 400 mg/day achieved this in 73.6% of patients, in Monte Carlo experiments. CONCLUSIONS: Minocycline at a dose of 400 mg/day is expected to be bactericidal. We propose a clinical trial for validation.
Multicenter Study to Assess the in vitro Activity of Tigecycline by Disk Diffusion Test against Clinical Isolates from Argentina
AbstractBACKGROUND: Tigecycline is a new antibiotic currently used in healthcare environments where multidrug resistance is prominent. Because there is a constant potential for resistance to emerge, survey studies are needed. METHODS: Isolates collected in 20 clinical laboratories from 4 states of Argentina between November 2005 and October 2006 were tested using the disk diffusion method as described by the CLSI. RESULTS: A total of 3,182 isolates were assessed. Gram-positive cocci represented 43.4% of the total isolates [Staphylococcus aureus (878), coagulase-negative staphylococci (255), Enterococcus spp. (201), Streptococcus spp. (47)], Enterobacteriaceae 39.6% and Acinetobacter spp. 11.1%. Tigecycline proved equally active against methicillin-resistant and methicillin-susceptible staphylococci, as well as against vancomycin-resistant and vancomycin-susceptible enterococci (100% of susceptibility for all Gram-positive bacteria tested). Tigecycline susceptibility for Enterobacteriaceae, other than Proteeae tribe and Serratia spp., ranged from 88 to 100%, including against strains with resistance to third-generation cephalosporins with phenotype of extended spectrum beta-lactamases (extended spectrum beta-lactamase-positive Escherichia coli 17.7% and extended spectrum beta-lactamase-positive Klebsiella pneumoniae 50.5%). Adopting a resistant breakpoint of 16 mm, 92% of the Acinetobacter isolates were susceptible to tigecycline. CONCLUSION(S): Tigecycline was active against a wide variety of bacterial species, including most of the multidrug-resistant Gram-negative and Gram-positive bacteria. Therefore, it could be a suitable option in the treatment of infections caused by these organisms in hospitalized patients.
Journal of Global Antimicrobial Resistance · 2019 · 1 citations · open access
The impact of serum protein binding on bacterial killing of minocycline
AbstractOBJECTIVES: Minocycline is increasingly used clinically for treating infections due to multidrug resistant bacteria. We previously reported that the serum protein binding of minocycline atypically correlated with total concentration using microdialysis, but the therapeutic implications of this finding remained unclear. The objective of this study was to ascertain the functional impact of serum protein binding on bacterial killing. METHODS: Time-kill experiments using 4 strains of Acinetobacter baumannii were conducted comparing the activity of minocycline in mouse serum (50 mg/L) and 50% cation-adjusted Mueller-Hinton broth (CA-MHB) (4 mg/L). As a control, similar experiments were also conducted for a clinically achievable levofloxacin concentration (4 mg/L) in serum and 50% CA-MHB (2 mg/L). Serial samples were collected in duplicate over 6 hours, and bacterial burden was determined by quantitative culture. RESULTS: Minocycline exhibited concentration-dependent bactericidal activity against the reference strain in mouse and human serum. Despite using approximately 10× the peak concentration associated with clinical dosing, only moderate bacterial killing was observed. All the minocycline killing profiles in serum were inferior to those observed in CA-MHB. In contrast, the reduction in bactericidal activity seen with levofloxacin was less dramatic. CONCLUSION: Antimicrobial activity of minocycline was dramatically reduced in the presence of serum, which corroborated with our atypical serum protein binding findings. If validated, these results implied dose escalation might not the best approach to improve the clinical efficacy of minocycline for bacteremia. Future investigations will focus on the specificity and mechanism(s) of minocycline protein binding.
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.
