Peptides›Cognitive, Immune›Cortistatin

Cortistatin

/ Endogenous somatostatin-family neuropeptide; binds somatostatin receptors SSTR1 through SSTR5 with comparable affinity to somatostatin, plus the ghrelin receptor (GHS-R1a) and (in mast cells) MrgX2 — a broader receptor profile than somatostatin

TIER 3 · PreclinicalN = 0 · TESTING PENDING

ALIAS · CST-17 · CST-29 · Cortistatin

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Research use onlyAny dose figures below describe what specific cited studies used, reported factually. Nothing on this page is guidance for human use.READ FIRST →

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§ A · Identity

Primary sequencePCKNFFWKTFSSCK (CST-17 includes additional N-terminal residues)

MW · —CLASS · Endogenous somatostatin-family neuropeptide; binds somatostatin receptors SSTR1 through SSTR5 with comparable affinity to somatostatin, plus the ghrelin receptor (GHS-R1a) and (in mast cells) MrgX2 — a broader receptor profile than somatostatinCATEGORY · Cognitive, Immune

Tier 3. Endogenous somatostatin-family neuropeptide with rodent and in-vitro pharmacology covering sleep modulation, anti-inflammatory effects, and somatostatin-receptor cross-talk. No FDA-approved cortistatin therapeutic; clinical translation has been limited compared to its better-known relative octreotide and the multireceptor analog pasireotide.

§ B · Mechanism of action

Cortistatin shares the C-terminal FWKT motif with somatostatin and binds all five somatostatin receptors with comparable affinity. Distinguishing pharmacology comes from additional binding to the growth hormone secretagogue receptor (GHS-R1a, the ghrelin receptor, with antagonist or weak partial agonist behaviour depending on assay) and to the mast cell receptor MrgX2. In rodent CNS, intracerebroventricular cortistatin produces slow-wave sleep enhancement (the basis for the name, from cortical sleep effects) and locomotor depression that distinguish it from somatostatin. Peripheral effects include anti-inflammatory and immunomodulatory actions in models of sepsis, colitis, and arthritis.

§ C · Human clinical evidence

Tier 3. Rodent literature establishes sleep-modulating, anti-inflammatory, and somatostatin-receptor-related endocrine effects. No published Phase 1 or later human trials of cortistatin as a therapeutic.

§ D · Primary literature

PubMed8622767de Lecea L et al. — A cortical neuropeptide with neuronal depressant and sleep-modulating properties · Nature · in-vitroOriginal isolation and characterisation of cortistatin from rat cortex as a somatostatin-related neuropeptide with cortical sleep-modulating and neuronal depressant activity distinct from somatostatin.Limitations: Discovery paper; rodent CNS and in-vitro electrophysiology only.1996

PubMed21734355Souza-Moreira L et al. — Neuropeptides as pleiotropic modulators of the immune response · Neuroendocrinology · reviewReview of neuropeptide immunomodulation including cortistatin actions in models of sepsis, arthritis, colitis, and autoimmune disease via somatostatin-receptor and ghrelin-receptor pathways.Limitations: Narrative review; preclinical evidence only.2011

§ F · Safety signal

No formal human safety database. Class concerns from somatostatin-receptor agonism (gallbladder motility, glucose tolerance, bradycardia) may apply by analogy; the additional GHS-R1a and MrgX2 engagement adds receptor-axis effects not seen with selective somatostatin analogs.

§ H · Regulatory status

Regulatory status

FDA status:: Not FDA-approved

§ I · Notable gaps and controversies

Cortistatin is sometimes marketed by research-chemical vendors with claims of sleep enhancement or anti-aging effects extrapolated from rodent ICV studies. The translational distance between rodent intracerebroventricular dosing and any peripheral human exposure is large, and no published human PK or PD data exist. The MrgX2 binding observation is mechanistically interesting but raises mast-cell-mediated adverse-event concerns that have not been characterised in vivo.