DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for acromegaly — screening already-approved drugs against its 12-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAcromegaly maps to a 12-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
approvedOctreotideApproved drug
Structures already discussed alongside acromegaly in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
dopamine receptor D4 (DRD4) — DRD4 is one of the genes in this disease's Open Targets module — part of the target space DeCure's repurposing candidates point at. The protein backbone is drawn as a cartoon. The structure has nemonapride bound in it, shown as sticks.
Loading structure…
helix sheet aqddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5WIU · 1.962 Å · ligand Nemonapride (AQD). Experimental structure, not a prediction.
What the evidence adds up to
Octreotide, a somatostatin analogue, was studied in 189 acromegalic patients treated for a median of 24.2 weeks across 23 centres. Clinical response was 88%, irrespective of dose or treatment duration. Serum growth hormone fell in 94% of 182 patients, from a mean of 39.4 µg/L to 12.2 µg/L; levels below 5 µg/L were reached in 45%. IGF-I fell in 92% of 99 patients, from 5.62 U/mL to 2.64 U/mL, with suppression to 2 U/mL or lower in 46%. Pituitary tumour size decreased by more than 20% in 44% of 34 patients studied prospectively. Side effects, mostly transient loose stools, injection-site pain and abdominal discomfort, occurred in 37%; glucose tolerance worsened in 48% of 25 evaluated patients.
Oral octreotide absorption was tested in 75 healthy volunteers. A single 20 mg oral dose produced a mean peak plasma concentration of 3.77 ng/mL and an area under the curve of 16.2 h·ng/mL, comparable to 0.1 mg subcutaneous octreotide (3.97 ng/mL and 12.1 h·ng/mL). The median time plasma concentration stayed above 0.5 ng/mL was 7.67 hours for oral versus 5.88 hours for injection. Basal growth hormone was suppressed by 49% and GHRH-stimulated growth hormone by 80% after the 20 mg oral dose.
Later reviews note that octreotide is a mature drug with a favourable benefit-risk profile, used as adjuvant therapy after neurosurgery or as neoadjuvant treatment. However, some patients maintain disease activity despite available treatments. In a study of 113 acromegaly patients, goiter was found in 75.2%, hypertension in 57.5%, hypercholesterolemia in 51.0%, diabetes in 20.3%, ischaemic heart disease in 15.9%, and hypertriglyceridemia in 13.3%. The prevalence of goiter and diabetes was significantly related to the duration of uncontrolled acromegaly, and after three years the risk of developing at least one of these complications became significant.
What remains missing is a treatment that controls disease in the patients who do not respond to current somatostatin analogues, and a formulation that reduces the burden of injections. New analogues, chimeric compounds binding both somatostatin and dopamine receptors, and growth hormone receptor antagonists are under investigation, but controlled trial data in treatment-resistant patients are still needed. The dissociation between antisecretory and antiproliferative effects of somatostatin analogues also requires clarification.
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 · 1991 · 237 citations
Long-term Treatment of 189 Acromegalic Patients With the Somatostatin Analog Octreotide
AbstractBACKGROUND: We wanted to determine the clinical and biochemical effects of long-term therapy with the somatostatin analog octreotide in 189 acromegalic patients. METHODS: Patients were treated at 23 medical centers for 6 days to 231 weeks (median, 24.2 weeks) with varying octreotide dosages (100 to 1500 micrograms/d; median, 300 micrograms/d). Serum growth hormone and insulin-like growth factor I (IGF-I) concentrations before and at the end of the study were compared, and correlations between the response to treatment with total daily dosage and duration of treatment were sought. RESULTS: The clinical response rate was 88%, irrespective of dosage or treatment duration. Serum growth hormone levels decreased in 172 (94%) of 182 patients and IGF-I levels decreased in 91 (92%) of 99. The mean pretreatment growth hormone level was 39.4 +/- 4.4 micrograms/L and decreased to 12.2 +/- 1.5 micrograms/L. Growth hormone levels decreased to less than 5 micrograms/L in 82 (45%) of 182 patients. The pretreatment IGF-I level was 5.62 +/- 0.41 U/mL and decreased to 2.64 +/- 0.19 U/mL; suppression to 2 U/mL or lower occurred in 46 (46%) of 99 patients. The degree of growth hormone suppression was associated with longer treatment duration but not with the total octreotide dosage per day. In 34 patients studied prospectively, pituitary tumor size decreased by greater than 20% in 15 (44%). Side effects occurred in 37% of patients and were most commonly transient loose alcoholic stools, pain at the injection site, and abdominal discomfort; severity was mild to moderate. Glucose tolerance was unchanged or improved in 52% and declined in 48% of 25 patients evaluated. CONCLUSIONS: Octreotide is an effective treatment for acromegaly that may be used as primary therapy or after surgery and/or pituitary irradiation.
The Journal of Clinical Endocrinology & Metabolism · 2012 · 157 citations · open access
Oral Octreotide Absorption in Human Subjects: Comparable Pharmacokinetics to Parenteral Octreotide and Effective Growth Hormone Suppression
AbstractCONTEXT: Oral administration of a novel octreotide formulation enabled its absorption to the systemic circulation, exhibiting blood concentrations comparable to those observed with injected octreotide and maintaining its biological activity. OBJECTIVES: The aim of the study was to determine oral octreotide absorption and effects on pituitary GH secretion compared to sc octreotide injection. DESIGN: Four single-dose studies were conducted in 75 healthy volunteers. INTERVENTION: Oral doses of 3, 10, or 20 mg octreotide and a single sc injection of 100 μg octreotide were administered. MAIN OUTCOME MEASURE: We measured the pharmacokinetic profile of orally administrated octreotide and the effect of octreotide on basal and stimulated GH secretion. RESULTS: Both oral and sc treatments were well tolerated. Oral octreotide absorption to the circulation was apparent within 1 h after dose administration. Escalating oral octreotide doses resulted in dose-dependent increased plasma octreotide concentrations, with an observed rate of plasma decay similar to parenteral administration. Both 20 mg oral octreotide and injection of 0.1 mg sc octreotide resulted in equivalent pharmacokinetic parameters [mean peak plasma concentration, 3.77 ± 0.25 vs. 3.97 ± 0.19 ng/ml; mean area under the curve, 16.2 ± 1.25 vs. 12.1 ± 0.45 h × ng/ml); and median time ≥ 0.5 ng/ml, 7.67 vs. 5.88 h, respectively). A single dose of 20 mg oral octreotide resulted in basal (P < 0.05) and GHRH-stimulated (P < 0.001) mean GH levels suppressed by 49 and 80%, respectively. CONCLUSIONS: The results support an oral octreotide alternative to parenteral octreotide treatment for patients with acromegaly.
Expert Opinion on Pharmacotherapy · 2013 · 40 citations
Octreotide for acromegaly treatment: a reappraisal
AbstractINTRODUCTION: Acromegaly is a rare disorder characterized by excess secretion of growth hormone (GH) generally caused by a pituitary macroadenoma and associated with reduced life expectancy if the disease is untreated. This article covers the recent available evidences published on octreotide , the first somatostatin analog introduced into clinical practice for the medical treatment of acromegaly. AREAS COVERED: This article discusses i) pharmacology of somatostatin and octreotide; ii) biochemical effects of regular octreotide and long-acting repeatable formulation; iii) tumor shrinkage effects of octreotide in acromegaly; iv) impact of octreotide on acromegalic clinical manifestations and chronic complications; v) safety of octreotide and vi) place of octreotide in the guidelines for acromegaly treatment. Full-text articles in the English language were selected from a PubMed search spanning 1984 - 2013, for keywords including 'octreotide,' 'acromegaly,' 'GH,' 'IGF-I,' and 'tumor shrinkage.' Reference lists in selected papers were also used to broaden the search. EXPERT OPINION: Octreotide is a mature drug with a consolidated favorable benefit versus risks profile in the treatment of acromegaly.
touchREVIEWS in Endocrinology · 2010 · 14 citations · open access
Implications of Somatostatin Analogues in the Treatment of Acromegaly
AbstractOctreotide has an important role in the medical management of acromegaly. Its place in the management of acromegaly as an adjuvant therapy after neurosurgery is well established with a well-demonstrated efficacy. It can also be used in certain clinical conditions as a neoadjuvant treatment. Clinicians and patients should be aware of the possible side effects of octreotide treatment.
Endocrine Connections · 2020 · 13 citations · open access
Novel therapies for acromegaly
AbstractAcromegaly is a systemic disease associated with increased morbidity and mortality. Most of these comorbidities can be prevented or delayed with adequate disease treatment. Although three modalities of treatment (surgery, medical treatment, and radiotherapy) are available and new drugs were approved in the last decades, there are still some patients that maintain disease activity despite treatment. Therefore, there is a need for novel therapies for acromegaly and for that purpose new formulations of currently used drugs and also new drugs are currently under study. In this review, we summarize the novel therapies for acromegaly.
The Journal of Clinical Endocrinology & Metabolism · 2023 · 12 citations · open access
New Treatments for Acromegaly in Development
AbstractAcromegaly treatment has greatly evolved in recent decades, but there are still patients whose acromegaly is not controlled with currently available treatments, and there is a need to improve the treatment burden. Fortunately, there are new treatments under development that may increase treatment efficacy and convenience.
Goiter, cardiovascular and metabolic disorders in patients with acromegaly
AbstractOBJECTIVE: This study evaluated the relationship between selected acromegaly complications such as IGF-1 serum concentrations at diagnosis as well as of controlled and uncontrolled disease. METHODS: A total of 113 acromegaly patients were enrolled to the study and the duration of active and uncontrolled disease was evaluated as a crucial cause of selected complications. RESULTS: Goiter, diabetes, hypercholesterolemia, hypertriglycerydemia, hypertension and ischemic heart disease were diagnosed in 85(75.2 %), 23(20.3 %), 48(51.0 %), 15(13.3 %), 65(57.5 %) and 18(15.9%) patients, respectively. Prevalence of goiter and diabetes was significantly related to the duration of uncontrolled acromegaly (p<0.01) as well as to the prevalence of hypertension and ischaemic heart disease (p0.05). After three years, there was a significant risk of an acromegaly patient being diagnosed at least with one of the above mentioned diseases (p<0.05) and such risk became more significant after four years (p0.05) related to the prevalence of the already mentioned complications. CONCLUSION: The treatment of acromegaly patients should be geared towards fulfilling all criteria for controlled disease, thereby alleviating potential complications and decreasing mortality.
Expert Opinion on Investigational Drugs · 2008 · 11 citations
New directions in pharmacological treatment of acromegaly
AbstractBACKGROUND/OBJECTIVES: The aim of treatment for acromegaly is to control tumour growth, relieve symptoms and ensure biochemical cure. With specific, well-tolerated medication, long-time primary or preoperative treatment should be discussed. METHODS: A PubMed search for literature ('somatostatin' and 'pituitary') was performed to explore different medical treatment options in today's clinics, which often use a combination of modalities. Clinical trial databases (ClinicalTrials.gov) were also searched for current clinical studies on acromegaly in order to reassess new directions in medical treatment. The cornerstone for medical treatment is somatostatin analogues (SAs). SAs control tumour growth and hormone hypersecretion in most patients. There seems, however, to be dissociation between the antisecretory and antiproliferative effects. New analogues with high affinity for other somatostatin receptor (SSTR) subtypes are being investigated. Chimeric compounds, which bind the SSTR as well as the dopamine receptor, are new potential alternatives. Patients not controlled on SAs (or dopamine agonists, or a combination) will be evaluated for treatment with the highly effective growth hormone receptor antagonist, as monotherapy or in combination with SAs. RESULTS/CONCLUSION: With the variety of medications we have today and those expected to come into clinical use in coming years, acromegaly can be controlled in almost all patients. There has already been a drift towards medical treatment also as a primary option, and it is to be expected that this will continue. Treatment should be tailored for the individual case, also taking into account long-term effects, convenience for the patient and costs for society.
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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