DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for methemoglobinemia — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMethemoglobinemia maps to a 2-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 methemoglobinemia 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
cytochrome b5 reductase 3 (CYB5R3) — CYB5R3 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 1UMK · 1.75 Å · ligand FLAVIN-ADENINE DINUCLEOTIDE (FAD). Experimental structure, not a prediction.
What the evidence adds up to
Among 28,478 transesophageal echocardiograms performed at the Mayo Clinic between 1999 and 2006, 19 cases of benzocaine-induced methemoglobinemia were identified, an incidence of 0.067% (95% CI 0.040–0.100%). Mean methemoglobin level in those 19 patients was 32% (SD 15). All were cyanotic with low oxygen saturations. Eighteen of the 19 received methylene blue (mean dose 1.3 mg/kg, SD 0.4), with resolution of symptoms and signs; one case resolved without treatment. Compared with a random sample of 190 patients who had the same procedure without methemoglobinemia, the patients who developed the condition were more likely to be hospitalised (89.5% vs 57.6%), anaemic (84.2% vs 44.7%), and have active systemic infection (68.4% vs 6.8%). The authors recommend minimising or avoiding benzocaine in those clinical contexts.
A retrospective case-control study from a single emergency department in Korea, covering 2002 to 2014, compared 15 patients with dapsone-induced methemoglobinemia (14 acute overdose, one chronic therapeutic use) with 19 patients exposed to other agents (sodium nitrites, indoxacarb, primaquine, lidocaine). Initial methemoglobin levels did not differ significantly between groups (38.5% vs 35.0%, p=0.456). After methylene blue, however, the dapsone group had a higher residual methemoglobin level (11.9% vs 1.7%, p=0.001) and required a larger total dose of methylene blue (455 mg vs 144 mg, p=0.006). Normalisation of methemoglobin took more than 72 hours in 93.3% of dapsone cases despite methylene blue. Five patients died of multiorgan failure, all in the dapsone group.
A poison centre series from New York City covering 2000 to 2024 included 185 cases in which methylthioninium chloride (methylene blue) was given for methemoglobinemia. Median methemoglobin level was 29% (IQR 19–42%). The most common causative agents were volatile nitrites (41%), local anaesthetics (15%), and dapsone (11%). Median single dose was 1 mg/kg (IQR 1–2, range 0.5–4). Multiple doses were given in 11% of cases, most often for volatile nitrites (n=7) or dapsone (n=6). Improvement after methylene blue was reported in 98% of cases (95% CI 96–100%). Adverse effects attributable to the drug occurred in nine cases (4.9%; 95% CI 4.6–5.1%), including one instance of haemolysis. Glucose-6-phosphate dehydrogenase activity was tested in only seven patients; two were deficient, and one of those did not improve after methylene blue. Two deaths occurred, both associated with sodium nitrite.
What is still missing: prospective data on optimal dosing and monitoring in dapsone-induced cases, routine G6PD testing before methylene blue administration, and trials comparing methylene blue with alternative treatments for patients with G6PD deficiency or refractory methemoglobinemia.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Internal Medicine · 2007 · 114 citations
Benzocaine-Induced Methemoglobinemia Based on the Mayo Clinic Experience From 28 478 Transesophageal Echocardiograms
AbstractBACKGROUND: The potentially life-threatening condition of methemoglobinemia is characterized by cyanosis, low pulse oximetric readings, and normal arterial Po(2) values. Acquired methemoglobinemia has been linked to the use of the topical anesthetic benzocaine in endoscopic procedures, including transesophageal echocardiography (TEE). Yet, the incidence of benzocaine-induced methemoglobinemia with TEE and the clinical factors associated with its development are unclear. METHODS: All cases of methemoglobinemia complicating TEE at our institution (from January 1, 1999, to July 1, 2006) were identified by a comprehensive review of medical records and echocardiography and pharmacy databases. RESULTS: During 90 months among 28 478 TEEs, 19 cases of methemoglobinemia were identified, with a mean +/- SD methemoglobin level of 32% +/- 15%. All patients were cyanotic, with low oxygen saturations. Eighteen of 19 patients received methylene blue (mean +/- SD dose, 1.3 +/- 0.4 mg/kg of body weight), with resolution of symptoms and signs. One of 19 cases resolved spontaneously. Compared with a random sample of 190 patients undergoing TEE, the age, sex, body mass index, left ventricular systolic function, and dose of sedation (midazolam hydrochloride, fentanyl citrate, or both) were similar in the 2 groups. However, study patients who developed methemoglobinemia were more likely to be hospitalized (89.5% vs 57.6%, P =.005), be anemic (84.2% vs 44.7%, P =.002), and have active systemic infection (68.4% vs 6.8%; P < .001) at the time of TEE compared with the random control cohort. CONCLUSIONS: In a large series of patients undergoing TEE, the incidence of methemoglobinemia is low (1 case per 1499 [0.067%; 95% confidence interval, 0.040%-0.100%]) and has a good outcome if promptly recognized and treated. Clinical factors associated with the development of methemoglobinemia include sepsis, anemia, and hospitalization. Minimizing or avoiding the use of benzocaine in these patients is recommended.
Difference of the clinical course and outcome between dapsone-induced methemoglobinemia and other toxic-agent-induced methemoglobinemia
AbstractCONTEXT: Acquired methemoglobinemia is a potentially fatal condition that leads to tissue hypoxia. Although the clinical features of methemoglobinemia depend on the methemoglobin levels, the clinical course would differ depending on the causative agents. OBJECTIVE: We attempted to clarify this issue by comparing the clinical course of methemoglobinemia caused by dapsone and that caused by other toxic agents. MATERIALS AND METHODS: A retrospective case-control study was performed. All patients with methemoglobinemia and who were admitted to the emergency department (ED) of our hospital from 1 January 2002 to 31 December 2014 were included. RESULTS: Of the 34 patients with methemoglobinemia, 15 ingested dapsone (14 with acute overdose and one with chronic therapeutic use) and 19 had been exposed to other toxic agents, such as sodium nitrites, indoxacarb, primaquine, and lidocaine. The clinical characteristics and the course of dapsone-induced and other toxic-agent-induced methemoglobinemia were compared. There was no significant difference in clinical presentation and methemoglobin level (38.5% vs. 35.0%, p = 0.456) upon their ED arrival between the two groups. However, the methemoglobin level after use of methylene blue and the total dose of methylene blue were higher in patients with dapsone-induced methemoglobinemia than in those with other agent-induced methemoglobinemia (11.9% vs. 1.7%, p = 0.001, 455 mg vs. 144 mg, p = 0.006). The majority of dapsone-induced methemoglobinemia (93.3%) required more than 72 h for normalization of the methemoglobin level, despite the use of methylene blue. Five of the study patients died due to multiorgan failure, and all of whom were inpatients with dapsone-induced methemoglobinemia. CONCLUSION: The clinical course of dapsone-induced methemoglobinemia was worse than that of other toxic-agent-induced methemoglobinemia despite no significant difference in their initial clinical presentation. Continuous treatment with serial monitoring of the serum methemoglobin is necessary for patients with dapsone-induced methemoglobinemia.
Clinical Toxicology · 2025 · 9 citations · open access
Effectiveness and tolerability of methylthioninium chloride (methylene blue) for the treatment of methemoglobinemia: twenty-four years of experience at a single poison center
AbstractIntroduction Despite the widely accepted use of methylthioninium chloride (methylene blue) to treat methemoglobinemia, data regarding clinical outcomes are sparse. We sought to better elucidate the efficacy and tolerability of methylthioninium chloride.Methods We identified all cases reported to the New York City Poison Center from 2000 to 2024 in which methylthioninium chloride was administered for methemoglobinemia. We extracted clinical data from these cases, which we assessed using primarily descriptive statistics.Results A total of 185 cases were included. The median methemoglobin level was 29% (IQR: 19–42%). Implicated xenobiotics were most frequently volatile nitrites (41%), local anesthetics (15%), and dapsone (11%). The median methylthioninium chloride dose was 1 mg/kg (IQR: 1–2 mg/kg; range: 0.5–4 mg/kg). Multiple doses of methylthioninium chloride were administered in 11% of cases, with a median total dose of 2 mg/kg (IQR: 2–3 mg/kg), the majority of which were associated with volatile nitrites (n = 7) or dapsone (n = 6). Improvement after administration of methylthioninium chloride was reported in 98% of cases (95% CI: 96–100%). Adverse effects attributable to methylthioninium chloride were reported in nine cases (4.9%; 95% CI: 4.6–5.1%), including one instance of hemolysis. Glucose-6-phosphate dehydrogenase activity was found to be deficient in two of seven patients tested, only one of whom did not improve after methylthioninium chloride. Two deaths occurred in this series, both associated with sodium nitrite exposure.Discussion Most patients with methemoglobinemia improved after 1–2 mg/kg of methylthioninium chloride, supporting current treatment recommendations. Despite few instances of glucose-6-phosphate dehydrogenase activity testing, major adverse effects attributable to methylthioninium chloride were extremely rare. A relatively large proportion of cases receiving multiple doses were associated with dapsone exposure.Conclusions In this series, methylthioninium chloride was both efficacious and well tolerated in patients with methemoglobinemia, with a single dose of 1–2 mg/kg being sufficient to treat most patients.
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.
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