Lanreotide: Somatuline, treatment for acromegaly and neuroendocrine tumors
A synthetic hormone shot given monthly that slows excess growth hormone and shrinks certain hormone-releasing tumors; FDA-approved drug.
A researcher, an agent, or an algorithm wrote down the sequence and picked a target to hit.
An AI model like OpenFold3 or AlphaFold built a 3D structure and scored how well it fits the binding site.
A second contributor repeated the computation on their own hardware and the scores matched.
A chemistry service or a researcher ordered the sequence, it was manufactured, and mass spectrometry confirmed the right molecule was produced.
A binding or activity measurement confirmed that it actually does what the computer predicted — or didn't.
What this is
Lanreotide (brand names Somatuline® Depot and Somatuline Autogel®, made by Ipsen) is a monthly or longer-interval injection used to treat acromegaly (a condition of excess growth hormone), certain types of neuroendocrine tumors, and carcinoid syndrome. It is a synthetic peptide that mimics somatostatin — a natural hormone that puts the brakes on several secretory processes in the body. Lanreotide is FDA-approved and EMA-approved for these indications. It is also known by its developmental code BIM-23014. The stored sequence XCYFWKVCT is a standard-letter approximation of the active cyclic molecule; the true structure contains a D-β-naphthylalanine residue at position 1, a D-tryptophan at position 4, a disulfide bridge between cysteines 2 and 7 forming the ring, and a C-terminal amide — none of which are visible in the raw sequence.
History
Lanreotide was developed by Ipsen during the 1980s–90s as a longer-acting alternative to octreotide (developed by Sandoz/Novartis), using β-2-naphthylalanine as a novel pharmacophore modification. An early formulation (BIM23014) had a half-life of approximately 90 minutes (Gomes-Porras and colleagues, International Journal of Molecular Sciences 2020). A sustained-release formulation followed, and then the self-forming Autogel — a supersaturated aqueous gel in which the molecule self-assembles into nanotube structures — extended dosing intervals to monthly or beyond when delivered by deep subcutaneous injection. European approval for acromegaly came in the early 1990s; the FDA approved lanreotide for acromegaly in 2007. The CLARINET Phase 3 trial, published in the New England Journal of Medicine in 2014 (Caplin and colleagues), established lanreotide for unresectable gastroenteropancreatic NETs, demonstrating that it reduced the risk of tumor progression or death by 53% compared with placebo (HR 0.47) — the first large prospective randomized trial to show anti-tumor disease stabilization with a somatostatin analog. FDA approval for GEP-NETs followed in 2014, and for carcinoid syndrome in 2017.
What it does
Lanreotide binds primarily to somatostatin receptor type 2 (SSTR2) and to a lesser extent SSTR5. These receptors are found on pituitary growth-hormone-secreting cells, on enterochromaffin and neuroendocrine tumor cells, and in other tissues. By activating SSTR2, lanreotide suppresses the release of growth hormone (GH) — which in acromegaly reduces elevated IGF-1 levels and reverses the tissue overgrowth, cardiovascular strain, and metabolic effects of the disease. In neuroendocrine tumors, SSTR2 activation slows cell division and reduces blood-vessel formation within the tumor, stabilizing disease without typically causing regression. In carcinoid syndrome, it suppresses release of serotonin and other mediators from enterochromaffin cells, reducing flushing and diarrhea. The Autogel depot formulation is designed to avoid the high concentration peaks associated with other injectable formulations, providing steadier exposure across the dosing interval.
Evidence
- Human: The CLARINET Phase 3 trial (Caplin and colleagues, NEJM 2014) randomized 204 patients with non-functioning well-differentiated gastroenteropancreatic NETs (grade 1 or 2, Ki-67 <10%) to lanreotide 120 mg every 28 days versus placebo; median progression-free survival was not reached in the lanreotide arm versus 18.0 months on placebo (HR 0.47, 95% CI 0.30–0.73, p=0.0002), a 53% reduction in the risk of progression or death. In acromegaly, a meta-analysis of long-acting somatostatin analog therapy reported GH normalization below 2.5 ng/mL in 57–67% of patients on lanreotide and IGF-1 normalization in 60–65% (Freda and colleagues, Journal of Clinical Endocrinology & Metabolism 2005). The ELECT Phase 3 trial (Vinik and colleagues, Endocrine Practice 2016) established carcinoid syndrome symptom control by showing that lanreotide 120 mg every 4 weeks significantly reduced the need for rescue short-acting octreotide compared with placebo over 16 weeks. More recent reviews continue to position lanreotide alongside ¹⁷⁷Lu-DOTATATE in the SSTR2-targeted treatment sequence for pancreatic NETs (Karimi and colleagues, npj Precision Oncology 2025).
- Animal: In SSTR2-positive NET xenograft models, lanreotide reduces tumor growth with confirmed anti-angiogenic effects (VEGF reduction). In a rat prostate tumor model, lanreotide was as effective as castration (Gomes-Porras and colleagues, International Journal of Molecular Sciences 2020), and therapeutic benefit was also observed in the hormone-resistance phase.
- In vitro: Mechanistic studies confirm SSTR2/5 binding and downstream suppression of cyclic AMP, calcium channel activity, and proliferative signaling.
Known effects
- GH/IGF-1 suppression in acromegaly — FDA-approved (normalization in majority of patients)
- GEP-NET disease stabilization — FDA-approved; 53% reduction in progression-or-death risk in CLARINET
- Carcinoid syndrome symptom control — FDA-approved (ELECT trial)
- SSTR2/5 agonism → anti-proliferative cell-cycle effects — established in clinical and preclinical data
- Flexible dosing interval (monthly to trimonthly) — in patients with stable disease on standard dosing
Safety signals
The safety profile of lanreotide closely resembles that of octreotide, as expected from the shared SSTR2/5 mechanism. Gallstone formation (cholelithiasis) is the most prominent long-term signal: a comparative pharmacovigilance analysis of the FDA Adverse Event Reporting System (Scientific Reports 2025) found a strong disproportionality signal for cholelithiasis with lanreotide (Reporting Odds Ratio 12.03, 95% CI excluding 1), and long-term clinical follow-up describes cholelithiasis in roughly 20–33% of lanreotide-treated patients (Gomes-Porras and colleagues, International Journal of Molecular Sciences 2020). Gastrointestinal symptoms — diarrhea, abdominal pain, loose stools, nausea — are common and were more frequently associated with lanreotide than with octreotide in the same FAERS analysis. Injection-site reactions occur with the deep subcutaneous Autogel formulation. Bradycardia and mild hyperglycemia (somatostatin suppresses insulin secretion) have also been reported. The same FAERS analysis found lanreotide carries comparatively lower cardiovascular and neoplastic safety signals than octreotide, and long-term tolerability over several years of treatment is generally considered acceptable.
Regulatory status
- US: Prescription-only. FDA-approved for acromegaly (Somatuline Depot® 60/90/120 mg SC, 2007), unresectable well-differentiated GEP-NETs (2014), and carcinoid syndrome (2017). Three separate approved indications.
- EU: EMA-approved as Somatuline Autogel® for acromegaly and NETs.
- WADA: Somatostatin analogs are not listed on the WADA Prohibited List for general sport; their use in medical indications does not require a Therapeutic Use Exemption.
Related peptides
- Octreotide (/card/pep-10808) — the first marketed SSTR2/5 analog; available as octreotide LAR for monthly injection; same mechanism and primary indications.
- Somatostatin-14 (/card/pep-10641) — the endogenous parent hormone; short half-life (1–3 min) makes it unsuitable for chronic use, which drove the development of lanreotide and octreotide.
- Somatostatin-28 (/card/pep-10642) — the extended endogenous form with a longer sequence; also acts at SSTR2 but with different receptor subtype distribution.
- Pasireotide — pan-SSTR agonist (SSTR1/2/3/5); approved for Cushing's disease; broader receptor profile than lanreotide with distinct metabolic side-effect profile.
Mechanism
Lanreotide's full chemical name reflects a ring structure: [D-β-2-Nal¹]-Cys²-Tyr³-D-Trp⁴-Lys⁵-Val⁶-Cys⁷-Thr⁸-NH₂, with a disulfide bridge between Cys2 and Cys7. The β-2-naphthylalanine at position 1 provides hydrophobic stacking with SSTR2 and SSTR5 transmembrane helices, conferring nanomolar affinity (SSTR2 IC₅₀ ~0.5 nM). Upon SSTR2 binding, the receptor couples to Gi/o proteins, reducing intracellular cyclic AMP (cAMP), closing voltage-gated calcium channels, and blocking secretory vesicle exocytosis — the mechanism by which GH, serotonin, and other hormones are suppressed. The anti-proliferative effect operates through a separate pathway: SSTR2 activates protein tyrosine phosphatases (SHP1/PTP-η), which attenuate Ras/MAPK signaling and induce G1-phase cell cycle arrest by reducing CDK2/4 activity. The Autogel formulation disperses the peptide in a polysorbate/carmellose microsphere matrix; once injected deep subcutaneously, slow aqueous dissolution of the depot produces a flat pharmacokinetic profile across the monthly dosing interval, avoiding the concentration peaks associated with bolus injection.
Open questions
- Whether the progression-free survival benefit demonstrated in CLARINET translates to an overall survival benefit — extended follow-up data show a trend but no definitive OS signal.
- Whether lanreotide provides anti-tumor benefit in higher-grade (Ki-67 > 10%) G2/G3 NETs beyond hormonal symptom control.
- The role of lanreotide in SSTR2-negative tumors that emerge after progression, and optimal sequencing with mTOR inhibitors (everolimus) or peptide receptor radionuclide therapy (PRRT, e.g., ¹⁷⁷Lu-DOTATATE).
Research directions for this peptide, selected from the current sources — hypotheses you can explore and model. None of it is proven yet; tap any one to see the full thinking.
Does long-term lanreotide treatment reliably prevent growth of small pancreatic tumors in people with a hereditary tumor syndrome, and does this protection last beyond two years?
People with MEN1 syndrome develop multiple pancreatic tumors across their lifetime and often face repeated surgeries. If lanreotide can hold small tumors stable for many years, some patients might avoid or substantially delay operations, improving quality of life considerably.
Is lanreotide's exceptional binding strength mostly due to its pre-shaped ring structure rather than the usual flexible lock-and-key process?
If rigidity is the key, drug designers could copy that ring-constraining trick to make other peptide drugs bind more tightly and specifically, potentially reducing side effects and enabling lower doses in future somatostatin-targeting medicines.
Does the bulkier chemical group at position 1 in lanreotide make it grab onto one receptor subtype more tightly than octreotide does, creating different patient response patterns?
Many acromegaly patients do not fully respond to either drug. If this structural difference predicts who benefits from which agent, doctors could match patients to the right medicine from the start, saving months of ineffective treatment.
Does the amide group capping the tail of lanreotide make a specific contact with the somatostatin-2 receptor that is absent at the somatostatin-5 receptor?
If this end-cap is responsible for receptor selectivity, chemists could tune it to create drugs that hit only the desired receptor, reducing off-target effects and potentially improving efficacy in specific tumor types that express one subtype more than the other.
Could the tiny tubes that lanreotide naturally forms in solution be used to package and slowly release other cancer drugs at a tumor site?
If lanreotide can act as its own delivery vehicle, oncologists might one day inject a single preparation that both controls tumor secretion and delivers a targeted cancer-killing agent, without needing to develop an entirely new drug carrier from scratch.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.9837395548820496 | boltz-2 |
| ranking score | 0.800366222858429 | boltz-2 |
▸3-letter notation
▸recipeboltz-2 2.2.1
| parameter | value |
|---|---|
| model | boltz-2 2.2.1 |
| weights | — |
| hardware | vast_v100_32gb |
| mlx version | — |
| python | — |
| random seed | 1 |
| msa strategy | colabfold_local |
| runtime | — |
| predicted by | — |
| predicted at | 2026-05-22 |
▸citationbibtex
@peptide{pep10981,
sequence = {XCYFWKVCT},
target = {sstr2},
author = {peptidemodel},
year = {2026},
status = {computed}
}