Prokineticin 2
An endogenous neuropeptide (Bv8) that signals through the prokineticin receptors; its loss causes Kallmann syndrome in people, and it also tunes the body clock, feeding and pain — a research peptide, not a drug
Prokineticin 2 (PROK2), also known as Bv8, is a small human peptide with an unusually wide reach. It belongs to the AVIT family — named for the conserved amino acids at its start — and works through two receptors, PROKR1 and PROKR2. Its best-defined role in people is in development: when the PROK2 or PROKR2 gene is broken, the GnRH neurons that drive puberty fail to migrate into the brain properly, causing Kallmann syndrome — absent puberty and a reduced or absent sense of smell. Beyond that, prokineticin 2 is a core signal of the body clock, carrying the daily rhythm out of the brain’s master clock, and it shapes neurogenesis, feeding and energy balance, pain, mood and the growth of new blood vessels. PROK2 is an endogenous peptide studied as a research tool and drug target; it is not an approved medicine and has not been given to people as a treatment.
No established human dose Details ↓
Recommended Dosing
No established human dose
Prokineticin 2 is an endogenous human peptide that has never been given to people as a treatment. The human evidence is genetic (mutations that cause Kallmann syndrome) and observational (blood levels), not administration; the interventional work is in animals and cells.
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What is it?
Prokineticins are a small family of secreted peptides — prokineticin 1 and prokineticin 2 — first recognised from frog-skin and snake-venom relatives and named for their ability to drive gut muscle movement. PROK2 (the mammalian version of the frog peptide Bv8) is about 81 amino acids long, held in a rigid shape by five disulfide bridges, and it signals through two closely related receptors, PROKR1 and PROKR2.
PROK2’s clearest role in humans comes from what happens when it is missing. Mutations that disable PROK2 or its receptor PROKR2 are a recognised cause of Kallmann syndrome — a developmental disorder in which the neurons that make gonadotropin-releasing hormone (GnRH) fail to migrate into the brain during development, so puberty does not start (hypogonadotropic hypogonadism) and the sense of smell is reduced or absent (because the olfactory bulbs are underdeveloped). The same migration machinery builds other parts of the brain: in mice, losing PROK2 or PROKR2 wrecks the migration of interneurons into the olfactory bulb, cutting their number by about three-quarters.
The inheritance of this is unusual and instructive. Many Kallmann patients carry only a single mutated copy of PROK2 or PROKR2, with incomplete penetrance — relatives with the same mutation can range from no symptoms to full-blown disease — and some cases are ‘digenic’, needing a second hit in another gene. A 2025 study that recalled carriers of rare PROK2/PROKR2 variants from a large hospital biobank confirmed the reproductive link and uncovered a new one: carriers of a common founder variant were more likely to have lower-gastrointestinal problems, fitting the peptide’s original role in gut muscle.
Away from reproduction, prokineticin 2 is a central signal of the circadian clock, relaying the daily rhythm out of the brain’s master clock to control sleep and activity; variants in its receptor have been associated with mood disorders such as depression and bipolar disorder in human genetic studies, in line with the clock’s link to mood. The pathway also regulates feeding and energy balance — changes in the PROK2 system shift food intake and insulin sensitivity, and circulating PROK2 has been tied to cardiometabolic risk and type 2 diabetes — as well as pain perception, including a recently described role in carrying pleasant-touch signals.
Because the PROK2 system touches so many tissues, its receptors are studied as drug targets in several directions at once — pain, the immune response, and cancer, where the Bv8 form drives new blood vessels and tumour growth. Those efforts use PROKR agonists and antagonists as tools; PROK2 itself is not being developed as a therapy.
Prokineticin 2 is an endogenous human peptide and a research and drug-target tool, not a medicine. No published study has given PROK2 to people as a treatment — the human evidence is genetics and blood levels — it is approved nowhere, and material sold online as ‘prokineticin 2’ or ‘Bv8’ is an unregulated research chemical. Nothing here is a dose or a therapy; this page records what the published science says about the peptide.
Mechanism of Action
Prokineticin 2 is an AVIT-family peptide that works through two receptors, PROKR1 and PROKR2. Through them it guides GnRH-neuron and brain-cell migration in development, carries the circadian rhythm, and tunes feeding, pain and mood — which is why its loss causes Kallmann syndrome and its receptors are drug targets.
PROKR1 and PROKR2 receptors
PROK2 (and its sister PROK1) signal through the G-protein-coupled receptors PROKR1 and PROKR2, widely expressed in brain and peripheral tissues — the two receptors through which its many effects run (PMID 36289651).
GnRH-neuron and brain migration
Loss-of-function mutations in PROK2 or PROKR2 disrupt GnRH-neuron migration and olfactory-bulb development, causing human Kallmann syndrome — absent puberty and anosmia (PMID 21037178) — and in mice wreck olfactory-interneuron migration (PMID 31132148).
Clock, mood and metabolism
PROK2 relays the circadian rhythm out of the master clock; its receptor is associated with mood disorders in human genetics (PMID 19544013), and the pathway regulates feeding, energy balance and cardiometabolic risk (PMID 33932486).
Published Research
These are studies of prokineticin 2 read from their PubMed abstracts on November 6, 2026. They include a 2025 human recall-by-genotype cohort of PROK2/PROKR2 variant carriers, reviews of the pathway in reproduction (Kallmann syndrome), energy metabolism and male infertility, a mouse study of its role in brain-interneuron migration, and a human genetic association with mood disorders. Prokineticin 2 has not been given to people as a treatment in any published study; the human evidence is genetic and observational.
PROK2/PROKR2 variants in a human biobank cohort
Carriers of rare PROK2/PROKR2 variants (25 carriers, 24 controls) recalled from a large hospital biobank underwent detailed evaluation. Male variant carriers were more likely to have sought fertility evaluation, and carriers of a common founder PROKR2 variant were more likely to have lower-gastrointestinal problems — a novel association fitting prokineticin 2’s known role in intestinal smooth-muscle function. The study confirmed the reproductive link and added a gastrointestinal one in the general population.
The prokineticin 2 pathway in human reproduction
A review of how PROK2 and PROKR2 control reproduction. Both PROK2- and PROKR2-deficient mice reproduce the human Kallmann-syndrome phenotype, and PROK2/PROKR2 mutations are found in people with Kallmann syndrome — implicating the pathway in GnRH-neuron migration — and also in normosmic GnRH deficiency. Mutations are usually heterozygous with incomplete penetrance or a ‘second hit’ (oligogenicity), and the pathway has pleiotropic roles in pain, circadian rhythms, blood-cell formation and immunity.
Prokineticin 2 in energy metabolism
A review of PROK2 in food intake and energy balance. The peptide is expressed in peripheral tissues and the brain and acts through PROKR1 and PROKR2; disturbing the pathway changes food intake, feeding behaviour and insulin sensitivity in preclinical models. In humans, PROK2/PROKR2 mutations (Kallmann syndrome) can be accompanied by obesity, and circulating PROK2 has been linked to cardiometabolic risk factors and type 2 diabetes — marking it as a regulator of energy homeostasis.
PROK2/PROKR2 and brain-interneuron migration
In mice, the PROK2/PROKR2 pathway was shown to be required for the migration of olfactory-bulb interneurons. Neural-stem-cell-derived neuroblasts travel from the subventricular zone to the olfactory bulb, and in PROK2 or PROKR2 mutant mice severe migration defects caused the loss of about three-quarters of the bulb’s GABAergic interneurons — the same machinery whose failure underlies the olfactory defects of human Kallmann syndrome.
PROKR2 and mood disorders
A case-control study in a Japanese population (151 bipolar, 319 major-depressive and 340 control subjects) found a significant association between the prokineticin 2 receptor gene (PROKR2) and both major depressive disorder and bipolar disorder, consistent with animal data linking PROK2 and its receptor to circadian and sleep regulation. The authors noted the sample was small and called for replication — an association, not proof of cause.
Prokineticin 2 and male infertility
A review of the prokineticin system in male reproduction. PROK1 and PROK2 act through PROKR1 and PROKR2 to regulate many functions — gut motility, circadian rhythm, neurogenesis, angiogenesis, pain and mood — and the system is important in the development and maturation of reproductive organs. The review frames PROK2 as a candidate marker and potential therapeutic target in male infertility, including azoospermia.
No Established Human Dose
Prokineticin 2 is an endogenous human peptide that has never been given to people as a treatment. The human evidence is genetic (mutations that cause Kallmann syndrome) and observational (blood levels), not administration; the interventional work is in animals and cells. No regulator has approved any dose, and the animal studies used PROK2 or receptor ligands at experimental amounts that do not carry over to people, so no amount is printed here.
What this rests on: PMID 40498399, PMID 21037178, PMID 31132148.
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 Prokineticin 2 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 Prokineticin 2 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 Prokineticin 2, 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 Prokineticin 2 stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Prokineticin 2. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
How long it stays in the body: a half-life of not established for humans; an endogenous signalling peptide. After about five half-lives almost none is left.
When effects appear: unknown; no source on this page gives a time to effect for Prokineticin 2. Results reported in the studies are under Published Research.
Source: half-life: PMID 40498399.
Side effects, and when to stop or get help
From the Side Effects section: No human adverse-event data exist: no published study has administered prokineticin 2 to people; In people, loss-of-function mutations in PROK2 or PROKR2 cause Kallmann syndrome — absent puberty and reduced smell (PMIDs 21037178, 40498399); The pathway influences pain, mood, feeding and blood-vessel growth, so its receptors are studied as drug targets in both directions (PMIDs 19544013, 33932486); Material sold online as ‘prokineticin 2’ or ‘Bv8’ is an unregulated research chemical of unverified content. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Prokineticin 2. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Prokineticin 2 is an endogenous peptide that has not been given to people as a drug, so there is no human safety profile; the points below reflect that research status”).
Interactions
Unknown: a PubMed search for human interaction studies of Prokineticin 2 (reviewed 2026-11-06) 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 Prokineticin 2 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. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a drug: Drugs@FDA and the openFDA label endpoint hold no record, and FDA GSRS and ChEMBL hold no substance record for prokineticin 2 (searched November 6, 2026)). 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
Prokineticin 2 is an endogenous peptide that has not been given to people as a drug, so there is no human safety profile; the points below reflect that research status.
Contraindications & Cautions
Prokineticin 2 has no approved use and no label. These points reflect its endogenous, research status.
Legal Status
Prokineticin 2 (Bv8) is an endogenous human peptide studied as a research compound and drug target; it is not a drug and is not approved in any country.
Frequently Asked Questions
?What is prokineticin 2?
An endogenous human peptide, also called Bv8, of the AVIT family. It is about 81 amino acids long and signals through two receptors, PROKR1 and PROKR2; it has wide roles in development, the body clock, feeding, pain and mood.
?What does it do?
In development it guides the migration of GnRH neurons and brain cells — when PROK2 or PROKR2 is broken, people get Kallmann syndrome (absent puberty and reduced smell) (PMID 21037178). It also carries the circadian rhythm and tunes feeding, pain and mood (PMIDs 33932486, 19544013).
?Is it a treatment for anything?
No. Prokineticin 2 is a research peptide and its receptors are drug targets — studied in pain, metabolism and cancer — but PROK2 itself is not given as a therapy. No human trial has administered it, and it is approved nowhere.
?Is it approved or available to buy?
No. Prokineticin 2 is not a medicine, has no FDA application or label, and is approved nowhere. Material sold online as prokineticin 2 or Bv8 is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source; this page records the published science.
References
- [mechanism] Stamou MI, et al. "Expanding the phenotypic spectrum of PROK2/PROKR2: a recall-by-genotype study." Hum Genet, 2025;144(7):761-773. PMID: 40498399.
- [review] Martin C, et al. "The role of the prokineticin 2 pathway in human reproduction: evidence from the study of human and murine gene mutations." Endocr Rev, 2011;32(2):225-46. PMID: 21037178.
- [review] Magnan C, et al. "Pleiotropic effects of prokineticin 2 in the control of energy metabolism." Biochimie, 2021;186:73-81. PMID: 33932486.
- [animal] Wen Y, et al. "The PROK2/PROKR2 signaling pathway is required for the migration of most olfactory bulb interneurons." J Comp Neurol, 2019;527(18):2931-2947. PMID: 31132148.
- [mechanism] Kishi T, et al. "Possible association of prokineticin 2 receptor gene (PROKR2) with mood disorders in the Japanese population." Neuromolecular Med, 2009;11(2):114-22. PMID: 19544013.
- [review] Petrella C, et al. "Prokineticin 2/PROK2 and Male Infertility." Biomedicines, 2022;10(10). PMID: 36289651.
- [other] UniProt Q9HC23 (PROK2_HUMAN), read November 6, 2026: prokineticin 2 is the product of the PROK2 gene, a secreted ~81-amino-acid peptide of the AVIT family (a conserved AVITGA N-terminus and five disulfide bridges); it signals through the G-protein-coupled receptors PROKR1 and PROKR2. https://www.uniprot.org/uniprotkb/Q9HC23/entry
- [other] Prokineticin 2, the mammalian homolog of the frog peptide Bv8, was characterized in the early 2000s as one of two AVIT-family prokineticins (with prokineticin 1) acting on the receptors PROKR1 and PROKR2; its biology and its role in Kallmann syndrome are set out in the reviews carded on this page (read November 6, 2026).
- [other] US FDA, Drugs@FDA and the drug label endpoint (openFDA), searched November 6, 2026: no application and no label record for prokineticin 2. It is an endogenous human peptide, not a registered drug; FDA GSRS and ChEMBL hold no substance record for it.
Sources & Citations
The six studies carded above were read from their PubMed records on November 6, 2026. Identity comes from UniProt (Q9HC23, gene PROK2); prokineticin 2’s AVIT-family structure, its PROKR1/PROKR2 receptors and its role in Kallmann syndrome are from the reviews and human genetic studies carded here; the absence of US approval and of a drug substance record from Drugs@FDA, openFDA, FDA GSRS and ChEMBL was checked 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.