Pasireotide
Also known as: Pasireotide Diaspartate · Pasireotide Pamoate · SOM230 · Signifor (brand) · Signifor LAR (brand)
Pasireotide is a synthetic cyclohexapeptide somatostatin analog with a substantially broader somatostatin receptor binding profile than Octreotide (also built on this site), including notably high affinity for somatostatin receptor subtype 5 (SSTR5). At Verified Peptides, we think this broader receptor profile is directly why Pasireotide was FDA-approved in December 2012 (as Signifor) as the first medication specifically approved for Cushing's disease — corticotroph pituitary tumors predominantly express SSTR5 rather than the SSTR2 subtype that Octreotide preferentially targets. A real Phase III trial (Colao et al. 2012, PMID 22397653, New England Journal of Medicine) found urinary cortisol normalization in 15-26% of patients depending on dose, a modest but clinically meaningful response given the disease's severity and limited alternatives. We also want to be direct about a substantial, well-documented tradeoff: hyperglycemia occurred in the majority of treated patients, a mechanistically explainable consequence of Pasireotide's broader receptor activity also suppressing insulin secretion more strongly than Octreotide. Research-grade material sold here is a separate product intended solely for laboratory research.
What is Pasireotide?
Pasireotide is a synthetic cyclohexapeptide somatostatin analog, originally developed by Novartis under the research code SOM230, designed to achieve a substantially broader somatostatin receptor binding profile than earlier somatostatin analogs like Octreotide, also built on this site. While Octreotide binds predominantly to somatostatin receptor subtype 2 (SSTR2) with secondary SSTR5 activity, Pasireotide binds with high affinity to four of the five human somatostatin receptor subtypes (SSTR1, SSTR2, SSTR3, and SSTR5, with no meaningful SSTR4 affinity), and notably shows approximately 40-fold greater affinity for SSTR5 than other somatostatin analogs.
At Verified Peptides, we want to directly explain why this receptor-binding difference matters clinically: Pasireotide was FDA-approved in December 2012 (as Signifor, subcutaneous injection) specifically for Cushing's disease in patients for whom pituitary surgery is not an option or has failed — making it the first medication ever specifically approved for this disease. This approval is directly attributable to Pasireotide's strong SSTR5 activity, since ACTH-secreting corticotroph pituitary tumors (the underlying cause of Cushing's disease) predominantly express SSTR5 rather than the SSTR2 subtype that Octreotide targets, which is why Octreotide itself is not an effective treatment for Cushing's disease despite being an effective somatostatin analog for other indications. A long-acting release formulation (Signifor LAR) was subsequently approved in December 2014 for acromegaly specifically in patients with an inadequate response to surgery.
Chemically, Pasireotide has molecular formula C58H66N10O9, molecular weight approximately 1047.23 g/mol, CAS number 396091-73-9, PubChem CID 9941444.
Pasireotide is marketed in two distinct salt/formulation forms depending on indication: pasireotide diaspartate (Signifor), a twice-daily subcutaneous injection used for Cushing's disease, and pasireotide pamoate (Signifor LAR), a monthly long-acting intramuscular depot formulation used for acromegaly. This dual-formulation approach mirrors a pattern seen with several other peptide drugs in this catalog, where an immediate-release formulation is used for initial or dose-titration purposes while a separately developed long-acting depot formulation is used for maintenance therapy.
Key Benefits & Mechanisms
Mechanism of action
Pasireotide's mechanism, like Octreotide's, involves somatostatin receptor agonism, but its substantially broader receptor-subtype engagement (SSTR1, SSTR2, SSTR3, and especially SSTR5) produces a correspondingly broader physiological effect profile. In Cushing's disease, SSTR5 activation on corticotroph pituitary tumor cells is proposed to directly suppress ACTH secretion, which in turn reduces adrenal cortisol production — the primary therapeutic rationale for its use in this specific disease, distinct from Octreotide's SSTR2-predominant mechanism, which is not effective at suppressing ACTH from these particular tumor cells.
We want to be direct about an important mechanistic tradeoff: this same broader receptor activity, including meaningful SSTR5 engagement on pancreatic islet cells, also more strongly suppresses insulin secretion (and, to a lesser extent, incretin hormone secretion) than Octreotide's more narrowly SSTR2-focused activity does, which is the direct mechanistic basis for Pasireotide's well-documented hyperglycemia risk, discussed further in the research summary below. This is a clear illustration of a broader pharmacological principle: a wider or more potent receptor-engagement profile that confers therapeutic benefit for one indication (Cushing's disease, via SSTR5) can simultaneously produce an unwanted effect via the same broad engagement acting on an unrelated tissue (pancreatic islets).
Pasireotide's insulin-suppressing effect operates through at least two distinct mechanisms: direct inhibition of insulin secretion from pancreatic beta cells via somatostatin receptors expressed on those cells, and suppression of incretin hormones (including GLP-1 and GIP, the same hormone pathway targeted therapeutically by GLP-1 receptor agonists like Exenatide, also built elsewhere in this catalog) that normally amplify glucose-stimulated insulin release. This dual mechanism helps explain why Pasireotide's hyperglycemic effect is both rapid in onset and difficult to fully counteract with standard antidiabetic approaches that rely on intact incretin signaling.
Research Summary
At Verified Peptides, we think Pasireotide has a real, rigorous, but honestly modest-in-magnitude efficacy evidence base for its primary approved indication, alongside a substantial and well-documented safety tradeoff. The pivotal citation is Colao et al. (2012, New England Journal of Medicine, PMID 22397653), the PASPORT-CUSHINGS trial, a double-blind Phase III study randomly assigning 162 adults with Cushing's disease across more than 60 sites internationally to receive subcutaneous pasireotide at 600 μg or 900 μg twice daily. At 6 months, urinary free cortisol normalized without dose adjustment in 15% of patients on the lower dose and 26% on the higher dose. We want to be direct that this normalization rate, while real and statistically robust, is more modest than some other pivotal trial results cited elsewhere in this catalog (for example, Octreotide's 55-68% IGF-1 normalization in acromegaly) — a difference we think reflects Cushing's disease's genuine treatment difficulty and the limited prior availability of any approved medical therapy, rather than any flaw in the trial itself.
We also want to be fully transparent about a substantial, well-documented safety tradeoff: in the pivotal trial population, hyperglycemia-related adverse events occurred in a majority of patients (68.4-73.0% in the Cushing's disease trials specifically), with grade 3 or 4 hyperglycemia in 13% and diabetes mellitus in 7% of patients, and hyperglycemia-related treatment discontinuation in 5.3-6% of patients. Nearly all patients, including those with normal glucose status at baseline, showed some degree of worsening glycemic control within the first two weeks of treatment. FDA labeling specifically recommends assessing glycemic status before starting treatment and intensifying antidiabetic therapy first in patients with poorly controlled diabetes, reflecting how seriously this mechanistically explainable risk is managed in clinical practice.
At Verified Peptides, we sell research-grade Pasireotide exclusively for laboratory research, and we think this compound is a genuinely useful illustration of how receptor-binding breadth can be a double-edged pharmacological property — conferring efficacy for a previously untreatable disease while simultaneously introducing a substantial, mechanistically related new risk.
We also want to note that the PASPORT-CUSHINGS trial's design included a specific dose-escalation feature reflecting real clinical practice: patients whose urinary free cortisol did not adequately decline by month 3 received an additional 300 μg twice daily on top of their randomized dose, meaning the reported 15% and 26% normalization rates reflect outcomes under a realistic, clinically responsive dosing protocol rather than a single fixed dose maintained regardless of response — a methodological detail relevant to interpreting how these efficacy figures would translate to real-world clinical use.
- A 12-month phase 3 study of pasireotide in Cushing's disease (2012) PubMed · PMID 22397653
Common Stacks
Lesser-Known Facts About Pasireotide
Pasireotide's cyclohexapeptide structure, incorporating non-standard amino acids including phenylglycine derivatives, represents a structurally distinct design approach from Octreotide's more directly somatostatin-sequence-derived octapeptide structure, reflecting a deliberate later-generation medicinal chemistry effort to engineer a specific, broader receptor-binding profile rather than simply further stabilizing the original somatostatin sequence.
Pasireotide's status as the first medication specifically approved for Cushing's disease reflects a broader pattern in rare and orphan disease drug development: prior to its 2012 approval, treatment for Cushing's disease relied entirely on pituitary surgery, radiation, or off-label use of other medications not specifically studied or approved for this indication, illustrating how a receptor-binding-profile difference discovered through structure-activity research can translate into a genuinely novel treatment option for a disease that previously lacked any dedicated approved pharmacotherapy.
The hyperglycemia risk profile difference between Pasireotide and Octreotide has motivated specific clinical management protocols, including proactive glucose monitoring schedules and preferential use of particular antidiabetic drug classes (such as DPP-4 inhibitors and GLP-1 receptor agonists, which work through incretin-pathway mechanisms less directly opposed by Pasireotide's insulin-suppressing activity) over other options in patients requiring Pasireotide treatment who develop hyperglycemia.
Purity & Sourcing Considerations
At Verified Peptides, we require independent third-party HPLC purity testing and mass spectrometry identity confirmation for every batch of research-grade Pasireotide we offer, with a Certificate of Analysis (COA) available for each lot. Given Pasireotide's inclusion of several non-standard amino acids within its cyclic structure, identity confirmation is particularly important to distinguish authentic Pasireotide from related but distinct somatostatin analogs.
We source exclusively from manufacturers operating under Good Manufacturing Practice (GMP)-aligned quality systems, and every lot is independently verified rather than accepted solely on a supplier's internal documentation. Researchers should always request and review the specific COA for the lot they receive, confirming purity percentage and molecular identity before use in any experimental protocol, and specifically noting which salt form (diaspartate or pamoate) a given lot represents, since these correspond to different clinical formulations with different intended release characteristics.
Storage & Stability
Lyophilized Pasireotide is stable when stored at -20°C, protected from light and moisture. At Verified Peptides, we ship lyophilized peptide with appropriate cold-chain packaging to preserve stability in transit.
Once reconstituted, solution should be stored refrigerated at 2–8°C and used within the timeframe indicated on the product's documentation, avoiding repeated freeze-thaw cycles, consistent with standard handling practices for the other somatostatin-pathway peptides in this catalog.
Frequently asked questions about Pasireotide
What is Pasireotide and how does it differ from Octreotide?
Both are somatostatin analogs, but Pasireotide binds a broader range of somatostatin receptor subtypes (including notably high SSTR5 affinity), while Octreotide binds predominantly SSTR2. This difference is why Pasireotide, but not Octreotide, is effective for Cushing's disease, and also why Pasireotide carries a substantially higher hyperglycemia risk.
Is Pasireotide FDA approved?
Yes. It was approved in December 2012 (as Signifor) for Cushing's disease — the first medication ever specifically approved for this disease — and in December 2014 (as Signifor LAR) for acromegaly.
What evidence supports Pasireotide's efficacy in Cushing's disease?
The pivotal PASPORT-CUSHINGS Phase III trial (Colao et al. 2012, PMID 22397653) in 162 patients found urinary cortisol normalization in 15% (600 μg dose) to 26% (900 μg dose) of patients at 6 months — a modest but clinically meaningful result given the disease's severity and the prior lack of any approved medical therapy.
What is the most significant safety concern with Pasireotide?
Hyperglycemia, occurring in the majority of treated patients (68-73% in Cushing's disease trials), with grade 3/4 hyperglycemia in 13% and diabetes mellitus in 7%. This is directly mechanistically linked to Pasireotide's broader receptor activity also suppressing insulin secretion.
Why does Pasireotide work for Cushing's disease when Octreotide does not?
Corticotroph pituitary tumors that cause Cushing's disease predominantly express somatostatin receptor subtype 5 (SSTR5) rather than SSTR2. Pasireotide has strong SSTR5 affinity, while Octreotide is predominantly SSTR2-selective, explaining the difference in clinical efficacy between the two.
How does Pasireotide compare to Octreotide in acromegaly specifically?
Head-to-head trials have found pasireotide LAR can achieve superior biochemical control compared to octreotide LAR in some acromegaly patient populations, though at the cost of a higher hyperglycemia rate, reflecting the same receptor-breadth tradeoff seen in its Cushing's disease use.
What monitoring is recommended before starting Pasireotide treatment?
FDA labeling recommends assessing glycemic status before starting treatment and intensifying antidiabetic therapy first in patients with poorly controlled diabetes, given the well-documented hyperglycemia risk associated with this compound.
What are the two formulation forms of Pasireotide and when is each used?
Pasireotide diaspartate (Signifor) is a twice-daily subcutaneous injection used for Cushing's disease. Pasireotide pamoate (Signifor LAR) is a monthly long-acting intramuscular depot formulation used for acromegaly.
Through what mechanisms does Pasireotide raise blood glucose?
Through at least two pathways: direct suppression of insulin secretion from pancreatic beta cells via somatostatin receptors, and suppression of incretin hormones (GLP-1 and GIP) that normally amplify glucose-stimulated insulin release, making the hyperglycemic effect both rapid and difficult to fully counteract with standard incretin-based antidiabetic drugs.
Legal & research status: Pasireotide is FDA-approved (as Signifor, since 2012, for Cushing's disease; as Signifor LAR, since 2014, for acromegaly). Material sold as a research compound is offered strictly for laboratory and research use, not for human consumption or therapeutic use.