DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for metabolic acidosis — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMetabolic acidosis maps to a 4-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 metabolic acidosis 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
carbonic anhydrase 1 (CA1) — CA1 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 phenylsulfonyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7Q0D · 1.24 Å · ligand methyl 4-chloranyl-2-(phenylsulfonyl)-5-sulfamoyl-benzoate (84Z). Experimental structure, not a prediction.
What the evidence adds up to
Metabolic acidosis can be induced by drugs, and the clinical outcomes range from mild to fatal. A 2015 review categorised drug-induced metabolic acidosis by pathophysiological mechanisms and individual drug characteristics, noting that occurrences are usually accompanied by comorbid conditions. In a 2013 case report, a 17-year-old with β-thalassaemia on deferasirox 30 mg/kg daily developed isolated hyperchloraemic metabolic acidosis (bicarbonate 12.9 mM, sodium 137 mM, chloride 111 mM, potassium 3.6 mM). Acidosis resolved after withdrawing deferasirox. The Naranjo adverse drug reaction scale rated the likelihood that deferasirox was responsible as probable. Eight cases of metabolic acidosis had been reported in patients treated with deferasirox, most with further features of renal tubular dysfunction.
A 2023 retrospective cohort study from a Melbourne emergency department examined decompensated metabolic acidosis diagnosed on arterial blood gas in adult patients between July 2011 and September 2020. Sodium bicarbonate therapy was given to a minority of patients and to those with more severe acidaemia. The median number of bicarbonate doses was one, given at a median total dose of 100 mmol and a median of 2.8 hours after the diagnostic blood gas. Only 42% of patients in the bicarbonate group had a subsequent blood gas measured; in those patients there was no significant change in pH, bicarbonate, or base excess. Bicarbonate therapy was not independently associated with mortality. The authors concluded that bicarbonate dose was stereotypical and not tailored to acidosis severity, assessment of effect was infrequent, and no correction of acidosis was seen.
A 2018 prospective observational study of 109 patients undergoing elective and emergency surgeries lasting more than two hours found that duration of surgery was significantly related to incidence of both intraoperative and postoperative metabolic acidosis. Among patients with operative duration greater than five hours, 14 of 16 (87.5%) had metabolic acidosis. Ringer lactate administration had a significant relationship with postoperative metabolic acidosis (p = 0.030), while normal saline did not. Total crystalloid administered had a significant relation to postoperative metabolic acidosis (p = 0.047). Colloid administration was positively related to both intraoperative (p = 0.019) and postoperative metabolic acidosis (p = 0.009).
What is still missing are systematic studies of titrated sodium bicarbonate therapy to inform current practice, as the 2023 study found no evidence that standard fixed-dose bicarbonate corrected acidosis or improved survival. No trial has established whether tailored dosing or earlier intervention changes outcomes. Patient stratification by cause of acidosis, renal function, and severity remains unaddressed in prospective controlled designs. Funding for such trials 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.
F1000Research · 2015 · 45 citations · open access
Drug-Induced Metabolic Acidosis
AbstractMetabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs' characteristics.
Journal of Clinical Pharmacy and Therapeutics · 2013 · 15 citations
Hyperchloraemic metabolic acidosis induced by the iron chelator deferasirox: a case report and review of the literature
AbstractWHAT IS KNOWN AND OBJECTIVE: Deferasirox is a new treatment of iron overload that is administered orally once-a-day, resulting in better acceptance in patients. Deferasirox-induced renal tubular dysfunction has been reported on very rare occasions. CASE SUMMARY: A 17-year-old adolescent with β-thalassaemia on deferasirox 30 mg/kg daily presented with isolated hyperchloraemic metabolic acidosis (bicarbonate 12·9 mM, sodium 137 mM, chloride 111 mM, potassium 3·6 mM). Acidosis resolved after withdrawing deferasirox. Naranjo adverse drug reaction scale suggested that the likelihood that deferasirox was responsible for acidosis was probable. Eight cases of metabolic acidosis have been reported in patients treated with deferasirox. In most cases, acidosis was associated with further features of renal tubular dysfunction. WHAT IS NEW AND CONCLUSION: We describe herein a case of metabolic acidosis in the setting of treatment with the deferasirox. Our case and the literature indicate a potential risk of kidney toxicity on this agent.
Critical Care and Resuscitation · 2023 · 2 citations · open access
Decompensated metabolic acidosis in the emergency department: Epidemiology, sodium bicarbonate therapy, and clinical outcomes
AbstractObjective: This article aims to describe the epidemiology of decompensated metabolic acidosis, the characteristics of sodium bicarbonate (SB) administration and outcomes in emergency department (ED) patients. Design: This is a retrospective cohort study. Setting: ED of a tertiary referral hospital in Melbourne, Australia. Participants: Adult patients presenting to the ED between 1 July 2011 and 20 September 2020 with decompensated metabolic acidosis diagnosed on arterial blood gas (ABG). Main outcome measures: We compared characteristics between those treated with or without SB. We studied SB administration characteristics, change in laboratory variables, factors associated with use and dose, and clinical outcomes. Results: < 0.01). The median number of SB doses in the SB group was one treatment. This was given at a median total dose of 100 mmol and at a median of 2.8 h after the diagnostic blood gas results. Only 42% of patients in the SB group had a subsequent blood gas measured. In such patients, there was no significant change in pH, bicarbonate, or BE. SB therapy was not independently associated with mortality. Conclusions: ABG-confirmed decompensated metabolic acidosis was rare but associated with a high mortality. SB administration occurred in a minority of patients and in more acidaemic patients. However, SB dose was stereotypical and not tailored to acidosis severity. Assessment of SB effect was infrequent and showed no correction of acidosis. Systematic studies of titrated SB therapy are required to inform current practice.
Journal of Evidence Based Medicine and Healthcare · 2018 · 0 citations · open access
STUDY OF METABOLIC ACIDOSIS IN PATIENTS UNDERGOING SURGERIES OF OPERATIVE TIME GREATER THAN 2 HOURS DURATION
AbstractBACKGROUND \nMetabolic acidosis is proven complication of major surgery, but very less significance is given to it. Metabolic acidosis has a \nsignificant effect in postoperative recovery and morbidity of patients undergoing major surgery. Metabolic acidosis has a say in \nproper functioning of cardiovascular, renal and pulmonary system, added to severe stress full condition related to postoperative \nperiod, it bring about major shift in the speedy recovery of patient. It becomes significantly important that metabolic acidosis \nin diagnosed as early as possible and corrective measures are taken immediately. \nMATERIALS AND METHODS \nStudy design is a prospective observational study. 109 patients who underwent elective and emergency surgeries in the \ndepartment of General Surgery, Govt. Medical College Kottayam was studied for a period of 3 months (2016). On arrival of the \npatient, a detailed history of the patient was taken, along with emphasis to the multiple factors in the history which could be \ncontributory to postoperative metabolic acidosis such as diabetic status, drug history, history of respiratory, cardiac and renal \nstatus. Basic preoperative laboratory investigation was carried out and its values were recorded. A preoperative arterial blood \ngas analysis (ABG) of the patient was done before patient was taken for surgery, values of which were recorded and analysed \nto rule out existing acidotic status of patient, if the patient is already having metabolic acidosis he was excluded from the study. \nA second ABG was sent at 2 hours after induction of anaesthesia, values of which was recorded, along with the values of \nintraoperative fluids, preoperative Hb, duration of surgery, type of surgery, blood transfusion and colloid administration given \nduring the time of anaesthesia. A third ABG was sent within six hours of completion of surgery and the values analysed, with \ndue notes on postoperative care done and the days of ICU stay, for analysis and comparison. \nRESULTS \nDuration of surgery was significantly related to incidence of both intraoperative and postoperative metabolic acidosis. When \ncross tabulation was done between operative duration and intra operative metabolic acidosis, it was found that 14(87.5%) \nsubjects of total 16 who had duration of greater than 5 hrs had metabolic acidosis. 10 (62.5%) individuals of operative duration \n2.01-3 hrs., 28 (73.7%) individuals from 3.01-4 hrs. group and 37 (94.9%) individuals from 4.01-5 hrs duration group were \nfound to have intra operative metabolic acidosis. On doing an independent t test for calculating the significance of each of total \ncrystalloid, normal saline and ringer lactate it was found that ringer lactate had a significant relationship with postoperative \nmetabolic acidosis, indicated by a p value of 0.030, while normal saline had no significant relation to postoperative metabolic \nacidosis. Still it is interesting to note that total crystalloid administered had a significant relation to postoperative metabolic \nacidosis indicated by a p value of 0.047. Colloid administration was also found to have a positive relationship with both intra \noperative (p value of 0.019) and postoperative metabolic acidosis (p value of 0.009). \nCONCLUSION \nThis study stresses the need of doing an intra operative blood gas analysis, in all prolonged surgeries, to analyse and begin \ncorrective measures intra operatively itself, such that patient has least postoperative morbidity and speedy recovery.
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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