Corticotropin-like intermediate peptide (CLIP)
The fragment left when ACTH is split into alpha-MSH, mapped in human brain and tumours, studied for REM sleep in rats, and a known source of error in ACTH tests
CLIP is ACTH without its front end: the piece left over when the pituitary's intermediate lobe, or a tumour carrying the enzyme PC2, cuts ACTH into alpha-MSH and CLIP. It cannot stimulate the adrenal gland. In people it has been found in brain, pituitary and ACTH-secreting tumours, where it can distort ACTH tests; in rats it increased REM-type sleep. It has never been given to a person.
No established human dose Details ↓
Recommended Dosing
No established human dose
No study read has given CLIP to a person. The human studies on this page measure the peptide the body or a tumour makes, in brain and pituitary sections, tumour extracts and blood, and the only human work that applied CLIP used fetal adrenal cells and blood cells in a dish.
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What is it?
Corticotropin-like intermediate peptide, almost always shortened to CLIP, is the back end of ACTH, its last 22 amino acids. ACTH is the 39-amino-acid pituitary hormone that drives cortisol release, and it is cut from a larger precursor protein, pro-opiomelanocortin (POMC). In tissues that carry the processing enzyme PC2, ACTH is cut again: its front 13 residues become alpha-MSH and the remainder becomes CLIP. The name comes from where it was first found in quantity, the intermediate lobe of the rodent pituitary, which processes ACTH this way as a matter of course.
There is a numbering wrinkle readers will meet straight away. Most papers, including every study carded here, call the peptide ACTH(18-39): residues 18 to 39 of ACTH, 22 amino acids beginning with arginine. UniProt's record of human POMC (P01189) lists the corticotropin-like intermediary peptide as POMC residues 156 to 176, which is ACTH 19-39, 21 amino acids beginning with proline, because the arginine at position 18 is part of the cleavage site. This page gives the UniProt sequence as its formula basis and shows the 22-residue ACTH(18-39) form beside it, since that is the molecule the research used.
CLIP lacks the part of ACTH that switches on the adrenal gland. That piece sits at the front of the hormone, and in the studies read CLIP did not raise steroid output from human fetal adrenal cells or aldosterone in sheep. In blood and pituitary extracts, a CLIP fraction reacted with ACTH antibodies but had very little adrenal activity. Corticotropin has its own entry on this site; studies that gave or measured ACTH itself are carded there, not here.
In people, CLIP has been measured in tissue rather than studied as a hormone in its own right. It has been mapped by antibody staining through the human hypothalamus, limbic system, brainstem and spinal cord, and it sits in the same anterior pituitary cells as delta sleep-inducing peptide. In healthy adult pituitary and in most pituitary tumours that cause Cushing's disease, little ACTH is converted to CLIP. Tumours elsewhere in the body that make ACTH, the cause of ectopic ACTH syndrome, can process it further, and in some of them CLIP is the main ACTH-derived product. Those tumours carry PC2, and pituitary tumours that make only ACTH do not.
That processing difference has a practical consequence. Many hospital ACTH tests use two antibodies, one aimed at each end of the hormone. A tumour that turns most of its ACTH into CLIP and alpha-MSH can upset those tests, and a review of POMC research warns that this can lead to misdiagnosis. The same problem has a large veterinary literature: horses with pituitary pars intermedia dysfunction, the equine form of Cushing's, make plenty of CLIP, and their CLIP binds the capture antibody of a common ACTH test, especially in autumn. A point-of-care assay that measures ACTH and CLIP together was validated in horses in 2026.
Most of what is known about CLIP's own actions comes from rats. Injected into the brain ventricles, it selectively increased paradoxical (REM-type) sleep while leaving slow-wave sleep alone, and the effect was traced to a part of the dorsal raphe nucleus in the brainstem that carries CLIP fibres. After restraint stress, rats slept more, and a phosphorylated form of CLIP rose in the same brain regions, which led one French group to argue that CLIP links stress to the sleep rebound that follows it. In other rat studies it raised hippocampal excitability, increased eating after a fast, blunted a prolactin surge and released digestive enzyme from pancreatic tissue in a dish.
Shorter pieces of CLIP have their own small literature. A fragment of residues 22 to 39 was identified in obese mice as an insulin-releasing factor called beta-cell-tropin, and the five-residue piece ACTH 20-24 lengthened REM episodes in rats. Those are different molecules, so their studies are listed under References and not carded.
CLIP has never been a medicine. No study read gave it to a person, and no human dose exists. The only human work that applied the peptide used cells in a dish. Drugs@FDA holds no record for it. It is a natural cleavage product of ACTH, a research reagent and an analyte that can confuse ACTH testing.
Mechanism of Action
CLIP is cut from ACTH by the enzyme PC2 and keeps none of the region that activates the adrenal gland; in rats it acts in the brain, most clearly on REM-type sleep, by a route that is not the melanocortin-4 receptor.
Cut from ACTH by PC2
Where PC2 is present, as in the rodent intermediate lobe and many ectopic ACTH tumours, ACTH is split into alpha-MSH and CLIP; pituitary tumours without PC2 release intact ACTH.
No adrenal action
CLIP lacks ACTH's front end, and in the studies read it did not raise cortisol, DHA or aldosterone.
REM-type sleep in rats
Injected into the brain, it increased paradoxical sleep through its N-terminal residues and the dorsal raphe nucleus; this has not been tested in people.
Published Research
These are studies of CLIP itself, read from their PubMed abstracts: measurements in human brain, pituitary, tumours and blood, three experiments on human or rat tissue in a dish, rat and sheep experiments that gave the peptide, a review and two equine assay studies. No study read gave CLIP to a person. Studies of ACTH are carded on the corticotropin entry, and studies of shorter CLIP fragments are listed under References.
Found in tumours behind ectopic ACTH syndrome
Ratter and colleagues used radioimmunoassays with chromatography to sort the ACTH-related peptides in human plasma, spinal fluid and tumour tissue. CLIP did not show up in the blood or spinal fluid profiles, but it was present, together with alpha-MSH, in tumours taken from patients whose Cushing's syndrome came from ACTH made outside the pituitary. Pituitary tumours studied in culture released ACTH and related peptides instead.
No steroid boost in human fetal adrenal cells
Human fetal adrenal cells were grown in culture and given a panel of hormones, CLIP among them, at concentrations well above those that work for ACTH in the same system. CLIP did not raise cortisol or DHA output. Given alongside an ACTH fragment, it slightly lowered cortisol production, which was one of only a few interactions the authors found.
Released digestive enzyme from rat pancreas
Isolated lobules of rat pancreas were exposed to synthetic CLIP across a thousand-fold concentration range. It increased the release of amylase and of newly made protein in step with the concentration, about as strongly as secretin or a cholinergic drug, without changing how much protein the cells made. A shorter piece lacking CLIP's first seven residues did not reproduce the effect, and the rat pancreas itself held material that ran with synthetic CLIP on chromatography.
More dreaming sleep in rats, unlike ACTH
This short French report compared ACTH with two of its fragments injected into the brain ventricles of rats. ACTH itself left the sleep-wake cycle unchanged. One fragment, des-acetyl-alpha-MSH, lengthened slow-wave sleep, while CLIP selectively increased paradoxical sleep, the stage linked with rapid eye movements and dreaming.
Blunted the prolactin rise caused by beta-endorphin
In rats, beta-endorphin injected into a brain ventricle raises blood prolactin sharply. Giving CLIP at the same time cut the peak by between about two-fifths and a half, depending on the amount, and alpha-MSH did so more strongly. Together the two fragments had an additive effect. The authors suggested that the way the pituitary cuts its precursor protein could tune prolactin release.
No effect on aldosterone in sheep
Sheep with an adrenal gland moved to the neck so its artery could be infused were given several peptides cut from POMC, CLIP included. ACTH roughly doubled aldosterone secretion. CLIP and the other fragments did nothing measurable to aldosterone in conscious animals with normal sodium intake, though the authors left open a longer-term role.
Shares cells with DSIP in the human pituitary
Human pituitary glands and stalks were stained for CLIP and for delta sleep-inducing peptide. About three-quarters of the CLIP-stained cells in the anterior lobe and in what remains of the intermediate lobe also held DSIP. Few CLIP fibres reached the posterior lobe. The authors proposed that the two peptides might work together on the sleep-wake cycle.
Mapped through the human brain
A monoclonal antibody against CLIP was used on human brain tissue. Stained cell bodies clustered in the base of the hypothalamus, and fibres spread through the hypothalamus, preoptic area, septum, amygdala, brainstem and spinal cord, with dense networks around the periaqueductal grey. The pattern matched earlier animal maps, and the authors linked these areas to sleep, pain and breathing and heart control.
Raised excitability in the rat hippocampus
Recordings from the hippocampus of freely moving rats showed that CLIP given into a brain ventricle doubled the size of the population spike in a key output region of the hippocampus. Once raised, the response could not be pushed higher by electrical tetanus, though long-term potentiation still appeared after the stimulus was turned down. ACTH and saline caused no such change.
A minor, low-activity fraction in pituitary and blood
Pituitaries from accident victims and plasma from patients with Nelson's syndrome were separated by HPLC and each fraction tested for both ACTH immunoreactivity and adrenal-stimulating activity. Full-length ACTH accounted for about four-fifths of the activity. A fraction that ran with CLIP reacted with the antibodies but had very little adrenal activity, consistent with CLIP lacking ACTH's steroid-releasing region.
Changed growth of activated human blood cells
Human peripheral blood mononuclear cells activated with a plant lectin were exposed to ACTH and several of its fragments, with and without dexamethasone. Without the steroid, ACTH(18-39) was the only peptide that changed how much the cells multiplied. In T cells activated another way, it deepened dexamethasone's suppression. IL-2 levels did not move.
Increased paradoxical sleep, through its front end
Rats injected into a brain ventricle just before an eight-hour recording spent about a fifth more time in paradoxical sleep after CLIP. Its N-terminal pieces had a similar effect, while its C-terminal piece did not, and slow-wave sleep was unchanged throughout. The authors concluded that the sleep effect sits in CLIP's first few residues.
Acted on a sleep centre in the brainstem
To find where CLIP acts, researchers injected it into the dorsal raphe nucleus of rats and used radiolabelled peptide to confirm it stayed there. It lengthened paradoxical sleep, but only when placed in the dorsolateral part of the nucleus, the part that carries CLIP-containing fibres. VIP worked across the nucleus and DSIP not at all.
Phosphorylated CLIP in pituitary and ectopic tumours
An HPLC method separated ACTH, CLIP and the forms of each carrying a phosphate on serine 31. In two of three tumours causing ectopic ACTH syndrome, CLIP forms outnumbered ACTH, while in five pituitary tumours causing Cushing's disease ACTH predominated. Phosphorylated forms made up a large share in both, and the phosphate did not disturb several commercial ACTH assays.
Tumours that make CLIP carry the enzyme PC2
Five human ACTH-secreting tumours outside the pituitary, in which CLIP made up 40 to 95 percent of the C-terminal ACTH material, all expressed messenger RNA for the processing enzyme PC2. Three pituitary tumours that made intact ACTH and no CLIP lacked it, as did a lung cancer cell line that left the precursor uncut. The finding fits the rodent pattern, where PC2 is what splits ACTH into alpha-MSH and CLIP.
Stress raised phosphorylated CLIP in sleep regions
Rats restrained for an hour at the start of their active period then slept more, with paradoxical sleep up by more than half over the next 12 hours. Right after the stress, phosphorylated CLIP in the dorsal raphe nucleus rose by about 95 percent, and four hours later it was up in the arcuate nucleus. Blood ACTH-and-CLIP immunoreactivity rose more than threefold with the restraint and returned to baseline by four hours.
Increased eating in fasted rats
ACTH and several of its pieces were injected into the brain ventricles of rats. ACTH and alpha-MSH reduced eating, while ACTH 18-39 and a shorter C-terminal piece produced a lasting rise in food intake, but only in rats that had fasted. In cells carrying the melanocortin-4 receptor, these C-terminal pieces neither activated it nor blocked ACTH, so the feeding effect runs through some other route.
A warning for ACTH testing
Lowry's review of six decades of POMC research covers how the same precursor is cut differently in different tissues. It closes with a caution relevant to patients: tumours that cause ectopic ACTH syndrome can process ACTH only partly and release large amounts of alpha-MSH and CLIP, which can interfere with two-site ACTH immunoassays and lead to misdiagnosis.
Equine CLIP binds a common ACTH test antibody
Horses with pituitary pars intermedia dysfunction are diagnosed partly by blood ACTH. Using mass spectrometry, this study showed that synthetic CLIP, like ACTH, bound the capture antibody of a widely used chemiluminescent ACTH assay, and that the horse's own CLIP, found in pony plasma taken in autumn, could be recovered from that antibody. CLIP may therefore inflate measured ACTH in horses.
A bedside test that measures ACTH and CLIP together
A point-of-care immunoassay that reads ACTH and CLIP at the same time was compared with the reference ACTH laboratory test in 28 horses over a year, including after TRH stimulation. Agreement was good overall, with correlation of 0.94 or better, but the gap between methods grew in autumn and at higher hormone levels. The device's within-run and between-run variation were about 8 and 14 percent.
No Established Human Dose
No study read has given CLIP to a person. The human studies on this page measure the peptide the body or a tumour makes, in brain and pituitary sections, tumour extracts and blood, and the only human work that applied CLIP used fetal adrenal cells and blood cells in a dish. Every experiment that gave the peptide to a living animal used rats, sheep or mice, so there is no human preparation and no human dose to state.
What this rests on: PMID 1849784, PMID 7962350, PMID 6270171, PMID 8402922.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Corticotropin-like intermediate peptide (CLIP) is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of Corticotropin-like intermediate peptide (CLIP) has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Corticotropin-like intermediate peptide (CLIP), before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Corticotropin-like intermediate peptide (CLIP) stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Corticotropin-like intermediate peptide (CLIP). What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
Unknown: no cited half-life and no label or trial duration on this page says how long Corticotropin-like intermediate peptide (CLIP) lasts or how long it was given. Results reported in the studies are under Published Research.
Side effects, and when to stop or get help
From the Side Effects section: The human studies read measured CLIP in tissue and blood; none gave it (PMIDs 1849784, 7962350); Human cells exposed to it in a dish were fetal adrenal cells and blood mononuclear cells (PMIDs 6270171, 8402922). Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Corticotropin-like intermediate peptide (CLIP). Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“CLIP has not been given to people, so no human side effects are known”).
Interactions
Unknown: a PubMed search for human interaction studies of Corticotropin-like intermediate peptide (CLIP) (reviewed 2026-11-03) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Corticotropin-like intermediate peptide (CLIP) products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Corticotropin-like intermediate peptide (CLIP)'s expected mass, 2,309.5 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a medicine: CLIP has been measured in human tissue and tumours (PMID 7921221) and given only to animals and cells, never to a person). Sport: Not on the 2026 List.
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
CLIP has not been given to people, so no human side effects are known.
Contraindications & Cautions
No product label exists. These cautions follow from the evidence.
Legal Status
CLIP is a natural cleavage product of ACTH and a research peptide; it is not approved as a medicine in any source read.
Frequently Asked Questions
?What is CLIP?
Corticotropin-like intermediate peptide: the C-terminal part of ACTH, left when ACTH is cut into alpha-MSH and CLIP. Most papers call it ACTH(18-39).
?Is CLIP the same as ACTH?
No. It is a piece of ACTH that lacks the front end needed to stimulate the adrenal gland, and in the studies read it did not raise cortisol or aldosterone. ACTH has its own entry.
?Why do some sources say 18-39 and others 19-39?
Research papers number it ACTH(18-39), starting at an arginine. UniProt lists it as ACTH 19-39, treating that arginine as part of the cut site. Both describe the same fragment.
?Does CLIP affect sleep?
In rats, injected into the brain, it increased REM-type (paradoxical) sleep. No study read tested this in people.
?Why does CLIP matter for ACTH blood tests?
Some tumours turn most of their ACTH into CLIP and alpha-MSH, which can upset two-antibody ACTH tests. In horses, CLIP binds a common ACTH test antibody, so a combined ACTH-and-CLIP assay has been developed.
?Is this the CLIP in immunology or cell biology?
No. The class II-associated invariant chain peptide of immune cells and the CLIP-170 microtubule protein share the abbreviation only; this page covers the ACTH fragment.
?Can you take CLIP?
No. It has never been given to a person in any study read, and no medicine contains it.
References
- [pubmed] Ratter SJ, et al. "Pars intermedia peptides: studies in adult humans." Ciba Found Symp, 1981;81:224-43. PMID: 6268379.
- [pubmed] Fujieda K, et al. "The control of steroidogenesis by human fetal adrenal cells in tissue culture. III. The effects of various hormonal peptides." J Clin Endocrinol Metab, 1981;53(4):690-3. PMID: 6270171.
- [pubmed] Beloff-Chain A, et al. "Evidence that the insulin secretagogue, beta-cell-tropin, is ACTH22-39." Nature, 1983;301(5897):255-8. PMID: 6296695.
- [pubmed] Marshall JB, et al. "Effect of corticotropin-like intermediate lobe peptide on pancreatic exocrine function in isolated rat pancreatic lobules." J Clin Invest, 1984;74(5):1886-9. PMID: 6209301.
- [pubmed] Chastrette N, et al. "[Hypnogenic effects of des-acetyl-alpha-MSH and CLIP (ACTH 18-39) in the rat]." C R Acad Sci III, 1985;301(10):527-30. PMID: 3004676.
- [pubmed] Wardlaw SL, et al. "Antagonism of beta-endorphin-induced prolactin release by alpha-melanocyte-stimulating hormone and corticotropin-like intermediate lobe peptide." Endocrinology, 1986;119(1):112-8. PMID: 3013583.
- [pubmed] McDougall JG, et al. "Effects of POMC-derived peptides on aldosterone secretion in vivo." Clin Exp Pharmacol Physiol, 1987;14(8):673-8. PMID: 3440325.
- [pubmed] Vallet PG, et al. "Distribution and colocalization of delta sleep inducing peptide (DSIP) with corticotropin-like intermediate lobe peptide (CLIP) in the human hypophysis." Neurosci Lett, 1988;90(1-2):78-82. PMID: 2842706.
- [pubmed] Zaphiropoulos A, et al. "Immunohistochemical distribution of corticotropin-like intermediate lobe peptide (CLIP) immunoreactivity in the human brain." Brain Res Bull, 1991;26(1):99-111. PMID: 1849784.
- [pubmed] Seidenbecher T, et al. "Neuronal transmission of hippocampal CA1 neurones is modulated by corticotropin-like intermediate lobe peptide [CLIP; ACTH(18-39)]." Peptides, 1993;14(6):1221-4. PMID: 8134304.
- [pubmed] Goverde HJ, et al. "Multiple forms of bioactive and immunoreactive adrenocorticotropin in human pituitary and blood of patients with Nelson's syndrome." J Clin Endocrinol Metab, 1993;77(2):443-7. PMID: 8393886.
- [pubmed] Pepper GM, et al. "The biologic activity of ACTH and related peptides on peripheral blood mononuclear cells is altered by the presence of dexamethasone." Cell Immunol, 1993;151(1):110-7. PMID: 8402922.
- [pubmed] Massias JF, et al. "Phosphorylated forms of adrenocorticotropin and corticotropin-like intermediary lobe peptide in human tumors." Eur J Endocrinol, 1994;131(4):341-6. PMID: 7921221.
- [pubmed] Vieau D, et al. "Expression of the prohormone convertase PC2 correlates with the presence of corticotropin-like intermediate lobe peptide in human adrenocorticotropin-secreting tumors." J Clin Endocrinol Metab, 1994;79(5):1503-6. PMID: 7962350.
- [pubmed] Wetzel W, et al. "Effects of CLIP (corticotropin-like intermediate lobe peptide) and CLIP fragments on paradoxical sleep in rats." Peptides, 1994;15(2):237-41. PMID: 8008628.
- [pubmed] el Kafi B, et al. "Is the nucleus raphe dorsalis a target for the peptides possessing hypnogenic properties?." Brain Res, 1994;637(1-2):211-21. PMID: 8180798.
- [pubmed] Bonnet C, et al. "Influence of a 1 h immobilization stress on sleep states and corticotropin-like intermediate lobe peptide (CLIP or ACTH18-39, Ph-ACTH18-39) brain contents in the rat." Brain Res, 1997;751(1):54-63. PMID: 9098568.
- [pubmed] Wetzel W, et al. "Effects of the CLIP fragment ACTH 20-24 on the duration of REM sleep episodes." Neuropeptides, 1997;31(1):41-5. PMID: 9574836.
- [pubmed] Al-Barazanji KA, et al. "C-terminal fragments of ACTH stimulate feeding in fasted rats." Horm Metab Res, 2001;33(8):480-5. PMID: 11544562.
- [pubmed] Lowry P. "60 YEARS OF POMC: Purification and biological characterisation of melanotrophins and corticotrophins." J Mol Endocrinol, 2016;56(4):T1-T12. PMID: 26643914.
- [pubmed] Knowles EJ, et al. "Short Communication: Identification of equine corticotropin-like intermediate lobe peptide (CLIP) binding to an adrenocortipcotrophic hormone (ACTH) assay capture antibody." Domest Anim Endocrinol, 2023;83:106785. PMID: 36745973.
- [pubmed] Hart KA, et al. "Validation of a point-of-care assay for simultaneous quantification of equine adrenocorticotropic hormone and corticotropin-like intermediate peptide." J Vet Intern Med, 2026;40(5). PMID: 42858361.
- [other] UniProt P01189 (COLI_HUMAN), pro-opiomelanocortin; peptide 156-176 is the corticotropin-like intermediary peptide (PVKVYPNGAEDESAEAFPLEF), ACTH residues 19-39. Read November 3, 2026. https://www.uniprot.org/uniprotkb/P01189/entry
Sources & Citations
Every study on this page was read from its PubMed record on November 3, 2026. The sequence and precursor positions come from UniProt P01189; formula and mass are computed from the sequence; regulatory status comes from Drugs@FDA (openFDA), read the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.