DeCure's autonomous AMR AI scientist is researching a drug-repurposing hypothesis for tuberculosis — 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 moduleTuberculosis 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
approvedMetforminApproved drug
Structures already discussed alongside tuberculosis in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of human CYP3A4 — Metformin has a real, experimentally solved structure in complex with this target (PDB 5G5J, 2.6 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 mf8drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5G5J · 2.6 Å · ligand Metformin (MF8). Experimental structure, not a prediction.
What the evidence adds up to
A registry-based retrospective case-series in Northern Ethiopia analysed 3,445 tuberculosis patient records from 2009–2010 to 2013–2014. Among these patients, 58% were male, the mean age was 33.88 years, and 18.8% were co-infected with HIV. Treatment outcomes were: 10.8% cured, 64.8% treatment completed, 3.5% died, 0.3% failed, 5.1% defaulted, and 15.5% transferred out. The overall treatment success rate was 89.5%, rising from 87% in 2009–2010 to 92.8% in 2013–2014, a 6.67% change over five years. For pulmonary TB, pulmonary negative TB, and extra-pulmonary TB, successful treatment rates ranged from 83.1% to 89%, 85.1% to 89.4%, and 87.4% to 92%, respectively, over the same period. The year of treatment was significantly associated with successful outcomes (p = 0.014).
A 2023 scoping review on candidate repurposing drugs for tuberculosis states that TB remains the main infectious cause of death and that new treatment options are needed. The review notes that repurposing existing drugs has potential for rapid and low-cost development of new treatment strategies and has proven successful for TB. Its stated aim is to identify candidates for clinical investigation by reviewing which established drugs used for non-TB indications show preclinical bactericidal activity against M. tuberculosis.
A 1954 article on current concepts in the treatment of pulmonary tuberculosis describes that rest and collapse therapy had been supplemented with antibiotics, chemotherapeutic drugs, and resectional surgery. It presents an evaluation of their relative merits and suggests a program of therapy.
No specific repurposed drug candidates, their response rates, or survival data are given in these abstracts. The registry study reports real-world outcomes under existing treatment, not a drug repurposing trial. The scoping review describes a plan to identify candidates but provides no results. What is missing is a completed clinical trial testing a specific repurposed drug for tuberculosis, with patient stratification and adequate funding to move from preclinical activity to human efficacy data.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Science Translational Medicine · 2014 · 545 citations
Metformin as adjunct antituberculosis therapy
AbstractThe global burden of tuberculosis (TB) morbidity and mortality remains immense. A potential new approach to TB therapy is to augment protective host immune responses. We report that the antidiabetic drug metformin (MET) reduces the intracellular growth of Mycobacterium tuberculosis (Mtb) in an AMPK (adenosine monophosphate-activated protein kinase)-dependent manner. MET controls the growth of drug-resistant Mtb strains, increases production of mitochondrial reactive oxygen species, and facilitates phagosome-lysosome fusion. In Mtb-infected mice, use of MET ameliorated lung pathology, reduced chronic inflammation, and enhanced the specific immune response and the efficacy of conventional TB drugs. Moreover, in two separate human cohorts, MET treatment was associated with improved control of Mtb infection and decreased disease severity. Collectively, these data indicate that MET is a promising candidate host-adjunctive therapy for improving the effective treatment of TB.
Research Square · 2019 · 0 citations · open access
Treatment outcomes and factors associated with “successful treatment” among tuberculosis patients at peripheral health settings of Northern Ethiopia: a registry-based retrospective case-series analysis.
AbstractAbstract Objective: Evidence on treatment outcomes and identifying factors facilitating treatment success through a register based retrospective study have significant contribution in the improvement of a national tuberculosis program. This study was aimed at determining treatment outcomes and factors associated with “successful treatment” outcomes. Results: A total of 3445 patient records were included. More than half, (58%) were males and the mean age was 33.88 ± 16.91 years (range: 0-90). From the total TB patients, 18.8% were HIV co infected. The treatment outcome of TB patients were 371 (10.8%) cured, 2234 (64.8) treatment completed, died 119 (3.5%) died, 9 (0.3%) failed, 178 (5.1%) defaulted and 534 (15.5%) were transferred out. The overall treatment success rate was 89.5%. The overall treatment success rate was 87% in year 2009-2010 to 92.8% in 2013-2014 with 6.67% change in the outcome indicator over the five years period. Among pulmonary TB, pulmonary negative TB and extra pulmonary TB the rate of successful treatment outcome was 83.1% to 89%, 85.1% to 89.4%, and 87.4% to 92%, respectively in the year 2009-2010 to 2013-2014. The percentage of the overall successful treatment outcomes were significantly associated with the year of treatment (p- =0.014).
Greater South Information System · 2019 · 0 citations · open access
Treatment outcomes and factors associated with "successful treatment" among tuberculosis patients at peripheral health settings of Northern Ethiopia: a registry-based retrospective case-series analysis.
AbstractAbstract Objective: Evidence on treatment outcomes and identifying factors facilitating treatment success through a register based retrospective study have significant contribution in the improvement of a national tuberculosis program. This study was aimed at determining treatment outcomes and factors associated with "successful treatment" outcomes. Results: A total of 3445 patient records were included. More than half, (58%) were males and the mean age was 33.88 ± 16.91 years (range: 0-90). From the total TB patients, 18.8% were HIV co infected. The treatment outcome of TB patients were 371 (10.8%) cured, 2234 (64.8) treatment completed, died 119 (3.5%) died, 9 (0.3%) failed, 178 (5.1%) defaulted and 534 (15.5%) were transferred out. The overall treatment success rate was 89.5%. The overall treatment success rate was 87% in year 2009-2010 to 92.8% in 2013-2014 with 6.67% change in the outcome indicator over the five years period. Among pulmonary TB, pulmonary negative TB and extra pulmonary TB the rate of successful treatment outcome was 83.1% to 89%, 85.1% to 89.4%, and 87.4% to 92%, respectively in the year 2009-2010 to 2013-2014. The percentage of the overall successful treatment outcomes were significantly associated with the year of treatment (p- =0.014).
Open Science Framework · 2023 · 0 citations · open access
Candidate repurposing drugs for tuberculosis: a scoping review
AbstractTuberculosis (TB) remains the main infectious cause of death and new treatment options are needed. Repurposing existing drugs has potential for rapid and low-cost development of new treatment strategies and has proven successful for TB. With this scoping review, we aim to identify candidates for clinical investigation to be repurposed for TB. We will review literature to explore which established drugs, used for non-TB indications, show preclinical bactericidal activity against M tuberculosis and have potential to be repurposed for treatment of TB.
Current Concepts in the Treatment of Pulmonary Tuberculosis
AbstractToday we are armed with more and better weapons against tuberculosis than at any time in the past. Time-honored rest and collapse therapy have been supplemented with antibiotics, chemotherapeutic drugs, and resectional surgery. This article presents an evaluation of their relative merits in the therapy of pulmonary tuberculosis. Current fundamental concepts are emphasized and a program of therapy is suggested.
Pharmacokinetics of Dasatinib in a Patient with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia During Treatment with Anti-Tuberculosis Therapy
AbstractAbstract Abstract 5006 Objectives: Dasatinib is a second generation protein-tyrosine kinase inhibitor (TKI) indicated for first line treatment of chronic myeloid leukemia (CML) and second line treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) in patients who are imatinib resistant or intolerant. In this study, we present the case of a patient with Philadelphia chromosome- positive ALL, intolerant to imatinib, who developed reactivated tuberculosis (TB) while receiving dasatinib during maintenance chemotherapy. The purpose of our study was to determine the effects of concomitant anti-TB therapy on dasatinib exposure by measuring plasma dasatinib levels using three different oral doses of the drug in this patient. Methods: The patient was treated with isoniazid, rifampin, ethambutol, pyrazinamide and pyridoxine for 2 months, followed by isoniazid, rifampin and pyridoxine for an additional 4 months. Dasatinib therapy was continued at the initiation of TB therapy using 100 mg po od, and titrated by 50 mg increments to 200 mg po od. Dasatinib plasma levels were measured prior to initiating anti-TB treatment and at regular intervals during concomitant treatment using three different dasatinib doses. Results: Eight days after initiation of anti-tuberculosis therapy, the apparent clearance of dasatinib had increased from 1410 to 2174 L/h at 100 mg. However, at 150 mg and 200 mg doses, apparent clearance had decreased to levels lower than baseline. As expected, the direction of peak plasma concentration changes was inverse to the changes in apparent clearance: Cmax values were 30 at baseline, and 22, 46, 102 ng/mL for the 3 doses of dasatinib during anti-TB therapy, respectively. Conclusions: Our findings suggest dasatinib clearance is increased by approximately 50% shortly after initiating anti-tuberculosis treatment and increasing the dose of dasatinib during anti-TB therapy was able to restore dasatinib plasma levels to those observed before initiation of anti-TB therapy. (This work was supported by an unrestricted grant from Bristol Myers Squib) Disclosures: No relevant conflicts of interest to declare.
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.
