Gut-hormone fragment for lab research (CCK octapeptide 2-8, desulfated)
A lab-made snippet of the gut hormone CCK, used to study how CCK tells the brain you're full and triggers digestion. Research tool only.
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.
Named peptide fragment — synthesized for research; ClinicalTrials.gov trials registered for parent compound or class
Fork this card to add platform evidence →
Endogenous peptide fragment — receptor binding/activity established in published literature; CT.gov evidence
Fork this card to add platform evidence →
What this is
Cholecystokinin Octapeptide (2-8) (desulfated) is a research-grade laboratory peptide used to study how the gut hormone cholecystokinin (CCK) talks to its two different receptors. CCK is the hormone the small intestine releases after a fatty or protein-rich meal — it triggers gallbladder contraction, drives the pancreas to release digestive enzymes, and signals "I've eaten enough" to the brain via the vagus nerve. This particular molecule is the seven-residue tail end of CCK (YMGWMDF) with one critical modification deliberately missing: the sulfate group that normally decorates the tyrosine. The stored sequence also omits the C-terminal amide (-NH₂) cap that is present on the biologically active form. Because the tyrosine sulfate is what gives native CCK its high-affinity grip on the CCK-1 receptor (the one that drives gallbladder, pancreas, and satiety responses), the desulfated form loses most of that activity while retaining binding at the CCK-2 receptor — making it a useful tool for separating those two pathways in the lab. It is not a therapeutic and has no approved human use (Rehfeld, Frontiers in Endocrinology, 2017; Miller and Desai, Frontiers in Endocrinology, 2021).
History
CCK was identified in 1928 by Ivy and Oldberg as the intestinal factor that contracted the gallbladder — "cholecystokinin" literally meaning "gallbladder-mover." A separate "pancreozymin" activity reported in 1943 was eventually shown to be the same molecule. In the 1960s, Viktor Mutt and Erik Jorpes at the Karolinska Institute sequenced the 33-residue form (CCK-33) after large-scale extraction from porcine small intestine and identified the sulfated C-terminal heptapeptide as the minimal sequence carrying full receptor activity (Reeve and colleagues, Annals of the New York Academy of Sciences, 1994; Chandra and Liddle, Current Opinion in Endocrinology, Diabetes & Obesity, 2007). Subsequent receptor pharmacology in the 1980s and 1990s established that the sulfate on the tyrosine is the primary determinant of CCK-1 receptor potency, while the CCK-2 (gastrin) receptor binds sulfated and desulfated forms with similar affinity (Miller and colleagues, Pharmacology & Therapeutics, 2008). Desulfated heptapeptide fragments like the molecule on this card entered the literature as tool compounds to dissect which CCK actions depend on sulfation (CCK-1) and which do not (CCK-2).
What it does
The native, sulfated heptapeptide reproduces the classical CCK actions — gallbladder contraction, pancreatic enzyme secretion, slowed gastric emptying, and vagal-afferent satiety signaling (Miller and Desai, Frontiers in Endocrinology, 2021). Removing the tyrosine sulfate, as in this card's sequence, collapses high-affinity binding at the CCK-1 receptor while leaving binding at the CCK-2 (gastrin) receptor largely intact (Miller and colleagues, Pharmacology & Therapeutics, 2008; Cawston and Miller, British Journal of Pharmacology, 2010). The practical consequence is that the desulfated heptapeptide is much weaker at producing the satiety, gallbladder, and pancreatic responses driven by CCK-1, and is used instead as a CCK-2-preferring ligand for in vitro and animal studies of receptor-subtype contributions.
Evidence
- Human: No therapeutic role. The only CCK-derived peptide with an approved human indication is sincalide — the sulfated CCK-8 octapeptide, used as a diagnostic agent for gallbladder imaging; it is a distinct molecule from the desulfated heptapeptide on this card (Miller and Desai, Frontiers in Endocrinology, 2021). Human pharmacology of the CCK-2 receptor has been studied with selective small-molecule antagonists rather than this peptide; Grasing and colleagues reported single- and multiple-dose pharmacokinetics and tolerability of the CCK-2 antagonist L-365,260 in healthy volunteers, alongside readouts on anxiety, hunger, and cognition (Journal of Clinical Pharmacology, 1996).
- Animal: The CCK-1/CCK-2 discrimination that distinguishes sulfated from desulfated CCK heptapeptide has been mapped extensively in rodent satiety, gallbladder, and gastric-acid models; mouse CCK-2 receptor structure and expression were characterized by Lay and colleagues (Biochemical and Biophysical Research Communications, 2000).
- In vitro: Sulfated CCK-8 binds the CCK-1 receptor with sub-nanomolar to low-nanomolar affinity; desulfation produces an approximately three-orders-of-magnitude loss of CCK-1 affinity while CCK-2 affinity is essentially preserved (Miller and colleagues, Pharmacology & Therapeutics, 2008; Cawston and Miller, British Journal of Pharmacology, 2010). This differential is the molecular basis for treating the desulfated heptapeptide as a CCK-2-preferring probe.
Mechanism
CCK-1 (CCKAR) and CCK-2 (CCKBR / gastrin receptor) are both Gq-coupled class A G-protein-coupled receptors that signal through phospholipase C, IP₃, intracellular calcium release, and protein kinase C (Miller and colleagues, Pharmacology & Therapeutics, 2008). They diverge sharply in how they read the ligand's N-terminal region: CCK-1 uses a binding pocket that makes direct contact with the sulfated tyrosine, so removing the sulfate severely reduces affinity, whereas CCK-2 does not require the sulfate and binds CCK-8, desulfated CCK-8, the tetrapeptide CCK-4, and gastrin with comparable affinity (Cawston and Miller, British Journal of Pharmacology, 2010; Rehfeld, Frontiers in Endocrinology, 2017). CCK-2 is expressed in the stomach (where it is the gastrin receptor driving acid secretion via histamine release from enterochromaffin-like cells), in brain regions implicated in anxiety, panic, and nociception, and ectopically in several tumor types — properties that have made CCK-2-binding peptide derivatives an active focus for radiolabeled imaging and targeted radiotherapy (Roosenburg and colleagues, Amino Acids, 2011; Fani and Maecke, Theranostics, 2012; Bian and colleagues, Theranostics, 2025). Native CCK peptides — including the heptapeptide — are cleared from circulation in minutes by proteolysis and renal excretion, which is why endogenous CCK acts mainly as a local vagal-paracrine signal rather than a long-range circulating hormone (Reeve and colleagues, Annals of the New York Academy of Sciences, 1994).
Known effects
- CCK-1 receptor binding — Sharply reduced versus the sulfated parent; the desulfated heptapeptide retains only weak CCK-1 activity (Miller and colleagues, Pharmacology & Therapeutics, 2008).
- CCK-2 receptor binding — Largely preserved; useful as a CCK-2-preferring ligand in vitro (Cawston and Miller, British Journal of Pharmacology, 2010).
- Satiety, gallbladder contraction, pancreatic enzyme secretion — Weak compared with sulfated CCK-8, because these effects are CCK-1-dominated (Miller and Desai, Frontiers in Endocrinology, 2021).
- Research scaffold for CCK-2-targeted radiotheranostics — The C-terminal CCK heptapeptide/octapeptide is the structural starting point for CCK-2 receptor imaging agents and targeted radiotherapy candidates against CCK-2-expressing tumors (Roosenburg and colleagues, Amino Acids, 2011; Fani and Maecke, Theranostics, 2012; Bian and colleagues, Theranostics, 2025).
Safety signals
The desulfated CCK heptapeptide has no human therapeutic exposure history of its own. Adjacent safety information in the literature covers the sulfated parent (sincalide — abdominal cramping, nausea, and transient gastrointestinal symptoms during diagnostic infusion) and CCK-2-targeted small-molecule antagonists studied in healthy-volunteer trials (Grasing and colleagues, Journal of Clinical Pharmacology, 1996). No carcinogenicity or chronic-toxicity dataset exists for the desulfated heptapeptide as a discrete agent.
Regulatory status
- US: No FDA-approved use for the desulfated heptapeptide. The only CCK-derived compound with an FDA indication is sincalide (sulfated CCK-8, brand name Kinevac), approved for diagnostic gallbladder scintigraphy and pancreatic exocrine function testing — a different molecule from the one on this card.
- Therapeutic CCK-1 agonists: Multiple development programs for obesity and gastrointestinal disorders reached clinical trials and were discontinued; no CCK-1 agonist has reached approval, with rapid receptor tachyphylaxis and a narrow tolerability window cited as the dominant failure modes (Miller and Desai, Frontiers in Endocrinology, 2021).
- WADA: CCK is not specifically named on the Prohibited List; the S2 category (peptide hormones, growth factors, and their mimetics) is written broadly enough that performance- or appetite-related off-label use of CCK-family peptides could fall within its scope.
Related peptides
- Gastrin — endogenous CCK-2 receptor agonist produced by gastric G-cells; shares the C-terminal Trp-Met-Asp-Phe-NH₂ pharmacophore with CCK, which is the molecular reason CCK-2 is also called the gastrin receptor (Miller and colleagues, Pharmacology & Therapeutics, 2008).
- Sincalide (sulfated CCK-8) — the active hormone analog approved as a diagnostic gallbladder-contraction agent; the direct contrast molecule for this card, with sulfation and the C-terminal amide intact.
- GLP-1 — postprandial gut hormone with overlapping satiety function; succeeded clinically as a weight-loss target where CCK-1 agonism repeatedly failed (Miller and Desai, Frontiers in Endocrinology, 2021).
Open questions
- Whether engineered CCK-2-selective peptide ligands built on the desulfated heptapeptide scaffold can deliver durable, on-target imaging or therapeutic effects against CCK-2-expressing tumors without engaging residual CCK-1 signaling (Roosenburg and colleagues, Amino Acids, 2011; Bian and colleagues, Theranostics, 2025).
- Whether allosteric CCK-1 modulators — distinct from orthosteric agonists like CCK-8 — can separate satiety from tachyphylaxis and tolerability limits, a question raised by repeated failures of full CCK-1 agonist programs (Cawston and Miller, British Journal of Pharmacology, 2010; Miller and Desai, Frontiers in Endocrinology, 2021).
- The relative contribution of central versus peripheral CCK-2 signaling to anxiety, panic, and nociception remains mechanistically implicated but clinically undruggable (Lay and colleagues, Biochemical and Biophysical Research Communications, 2000).
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.
Could swapping the missing sulfate on the end of this modified CCK fragment with a similar but enzyme-resistant chemical group make a stable version that fully activates the hunger-suppressing CCK receptor?
If true, this approach could yield a peptide-based appetite suppressant that works by mimicking a natural fullness signal, potentially offering a new route to treating obesity with fewer side effects than current drugs.
Is the apparent ability of this modified CCK fragment to weakly activate the gallbladder/satiety receptor (CCK-1) merely a result of using too-high concentrations in experiments, rather than a real biological interaction?
If true, results from past studies using this peptide to investigate appetite, anxiety, and digestion would need to be reinterpreted, and researchers could use the compound more confidently to study CCK-2-specific biology, including its roles in the brain's fear and reward circuits.
Could this desulfated gut-hormone fragment, which activates only the brain form of the CCK receptor and not the digestive form, help researchers map the specific brain pathways that cause anxiety and panic attacks?
If true, scientists could use this compound to cleanly study the brain circuits involved in anxiety and panic, without the confusing gut side effects of the natural hormone. This could accelerate development of better anti-anxiety drugs that target the CCK system.
Could this modified gut peptide interact with the main CCK digestion receptor at a completely different binding pocket from where the natural hormone docks, potentially explaining puzzling low-level activity seen in some experiments?
If true, this would reveal a new docking site on an important digestive receptor, potentially enabling chemists to design simpler, non-sulfated drugs that could be taken by mouth to treat obesity, pancreatitis, or irritable bowel syndrome.
▸full evidence table2 metrics
| metric | value | tool |
|---|---|---|
| ipTM | 0.9792879223823547 | boltz-2 |
| ranking score | 0.8055791854858398 | boltz-2 |
▸structural qualityopenfold3
| metric | value | note |
|---|---|---|
| gpde | 0.759 | global PDE — lower = better |
| disorder | NaN | fraction disordered |
▸3-letter notation
▸recipeboltz-2 1.0
| parameter | value |
|---|---|
| model | boltz-2 1.0 |
| weights | — |
| hardware | nvidia_nim_api |
| mlx version | — |
| python | — |
| random seed | — |
| msa strategy | none |
| diffusion samples | 1 |
| runtime | — |
| predicted by | mlx@peptide |
| predicted at | 2026-04-24 |
▸citationbibtex
@peptide{pep10708,
sequence = {YMGWMDF},
target = {cckar},
author = {peptidemodel},
year = {2026},
status = {bioassayed}
}