Where Every Research Peptide Came From: The Complete Origin Story of Each Compound in 2026

Every research peptide has an origin story — a specific moment in scientific history when a researcher, a lab accident, or a systematic screening program first identified a sequence of amino acids with remarkable biological activity. Understanding where peptides come from and how they were discovered provides essential context for researchers evaluating which compounds to study and why. It also reveals how decades of foundational science in one field can unexpectedly produce breakthroughs in another.

This article traces the origin and discovery of every major research peptide available today — from compounds isolated from human gastric juice in the 1990s to AI-designed molecules published in 2026. Each section covers who discovered it, when, where, what they were originally looking for, and how the compound evolved from an academic curiosity into a widely studied research tool. If you have ever searched for peptide history, who discovered BPC-157, or where do research peptides come from, this is the most comprehensive single resource available.

BPC-157: Discovered in Human Gastric Juice in Croatia (1993)

The story of BPC-157 begins in Zagreb, Croatia, in the laboratory of Professor Predrag Sikiric at the University of Zagreb School of Medicine. In the early 1990s, Sikiric’s team was investigating the protective properties of human gastric juice — the complex fluid produced by the stomach that aids digestion and protects the gastric lining from its own acid.

Gastric juice had long been known to have protective properties beyond simple digestion. Sikiric’s group isolated a specific 15-amino-acid sequence from a larger protein found in human gastric juice and designated it Body Protection Compound-157 — BPC-157. The “body protection” name reflected their early observation that this peptide fragment appeared to have broad protective effects on tissues exposed to various forms of damage.

The first published studies on BPC-157 appeared in 1993-1994, focusing on its ability to protect the gastric mucosa from damage caused by NSAIDs, alcohol, and other insults. What made BPC-157 unusual from the very beginning was the breadth of tissues it appeared to affect. Most peptides discovered from gastric sources had effects limited to the GI tract. BPC-157, in contrast, showed activity in tendon repair, muscle healing, bone fracture recovery, nerve regeneration, and vascular repair in subsequent preclinical studies — a range of effects that was nearly unprecedented for a single peptide.

Over the following three decades, Sikiric’s laboratory published more than 100 peer-reviewed papers on BPC-157, establishing it as one of the most extensively studied healing peptides in preclinical research. The compound has never entered formal clinical trials for any indication, which means all published data comes from in-vitro and animal studies. Despite this, its consistent results across dozens of tissue types and injury models have made it one of the most widely used research peptides globally.

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TB-500: From Thymus Gland Research in the 1960s to Tissue Repair Science

The origin of TB-500 traces back to one of the most important immunological discoveries of the 20th century. In 1966, Allan Goldstein and Abraham White at the Albert Einstein College of Medicine in New York isolated a family of peptides from the thymus gland — the organ responsible for T-cell maturation and immune system development. They named this family “thymosins” and began characterizing the individual peptides within it.

Thymosin Beta-4, the parent molecule of TB-500, was identified as a 43-amino-acid peptide that was one of the most abundant thymosins in the body. Initial research focused on its immunological functions, but a pivotal discovery in the 1990s shifted the scientific narrative dramatically. Researchers found that Thymosin Beta-4 was not just an immune peptide — it was present in virtually every cell type in the body and played a fundamental role in cell migration, wound healing, and angiogenesis (new blood vessel formation).

The connection to tissue repair came from the discovery that Thymosin Beta-4 binds to and sequesters actin monomers — the protein building blocks that form the structural skeleton of cells. By regulating actin dynamics, Thymosin Beta-4 promotes the cell migration that is essential for wound closure, tissue remodeling, and organ repair. TB-500 is a synthetic version of the active region (amino acids 17-23) of Thymosin Beta-4, designed to be more practical for research use than the full-length protein.

The cardiac repair research was particularly influential. Studies published in the 2000s showed that Thymosin Beta-4 / TB-500 could promote cardiac tissue regeneration after ischemic injury — a finding that generated enormous interest because the adult heart was long considered incapable of meaningful self-repair. This work, led in part by Deepak Srivastava’s lab at the Gladstone Institute, helped establish TB-500 as a serious research compound in regenerative medicine.

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GHK-Cu: A Copper Peptide Found in Human Blood Plasma (1973)

The discovery of GHK-Cu is one of the most elegant stories in peptide science. In 1973, biochemist Loren Pickart was studying the differences between blood plasma from young people versus older people. He observed that plasma from 20-year-olds caused old liver tissue to produce proteins characteristic of younger tissue — essentially, young blood was “rejuvenating” old cells in culture. Pickart set out to identify the specific factor responsible.

After extensive fractionation and purification work, Pickart identified a tiny tripeptide — just three amino acids: glycine-histidine-lysine — that had a powerful affinity for copper ions. He named it GHK-Cu (Glycyl-L-Histidyl-L-Lysine with copper). This copper peptide was present in human plasma at concentrations that declined dramatically with age — roughly 200 ng/mL in young adults but falling to approximately 80 ng/mL by age 60.

What made GHK-Cu extraordinary was the scope of its biological activity. Over the following decades, research revealed that this tiny three-amino-acid peptide could stimulate collagen synthesis, attract immune cells to injury sites, promote nerve regeneration, upregulate antioxidant enzymes, and — most remarkably — modulate the expression of over 4,000 human genes. The gene-regulatory activity was discovered through genomic studies conducted in the 2010s, which showed that GHK-Cu resets gene expression patterns toward a healthier configuration, upregulating repair and protective genes while downregulating genes associated with tissue destruction and inflammation.

Pickart’s original question — what makes young blood different from old blood — led to the discovery of one of the most broadly active peptides ever characterized. GHK-Cu’s journey from an observation about plasma aging to a compound studied for skin anti-aging, wound healing, COPD, hair growth, and even metastasis suppression is a testament to how following unexpected data can lead to transformative discoveries.

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Retatrutide: Born From Eli Lilly’s Multi-Receptor Agonist Program (2022–2023)

The origin of retatrutide is inseparable from the broader story of incretin-based obesity research, which itself traces back to the discovery of GLP-1 in the 1980s. Glucagon-like peptide-1 was first characterized by Jens Juul Holst at the University of Copenhagen and Joel Habener at Massachusetts General Hospital, who identified it as a gut hormone released after eating that stimulated insulin secretion and suppressed appetite. This discovery would eventually spawn an entire pharmaceutical category.

The first generation of GLP-1R agonists — exenatide (discovered from Gila monster venom by John Eng at the VA Medical Center in the Bronx in 1992) and liraglutide (engineered by Novo Nordisk) — proved the concept that targeting GLP-1R could treat diabetes and promote weight loss. The second generation brought semaglutide (Ozempic/Wegovy), also from Novo Nordisk, which was engineered with an albumin-binding fatty acid chain that extended its half-life to approximately one week.

The leap to dual agonism came from Eli Lilly’s research program, which produced tirzepatide — a molecule that activates both GLP-1R and GIPR simultaneously. The GIP (glucose-dependent insulinotropic polypeptide) receptor had been identified in the 1970s by John Brown at the University of British Columbia, but its potential as a weight loss target was not appreciated until the 2010s when research showed that GIP and GLP-1 together produced synergistic metabolic effects far exceeding either alone.

Retatrutide emerged from Eli Lilly’s next logical step: adding a third receptor to the dual agonist platform. Lilly’s medicinal chemistry team engineered a single peptide that could activate GLP-1R, GIPR, and the glucagon receptor (GCGR) simultaneously. The glucagon receptor had been known since the 1950s (glucagon itself was discovered by Charles Kimball and John Murlin at the University of Rochester in 1923), but glucagon was historically viewed as a counter-regulatory hormone that raised blood sugar — the opposite of what you would want in diabetes treatment. The insight that changed everything was the recognition that glucagon receptor activation also dramatically increases energy expenditure and hepatic fat oxidation, making it a powerful anti-obesity target when combined with GLP-1R-mediated appetite suppression.

Retatrutide’s first human data was published in 2023 (phase 2 trial results in The New England Journal of Medicine), showing up to 24% body weight reduction over 48 weeks — the highest figure ever reported for any obesity compound in controlled human studies at that time. The compound’s identifier during development was LY3437943.

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Tirzepatide: Eli Lilly’s Dual Agonist Breakthrough (2018–2022)

Tirzepatide’s development at Eli Lilly represented the first successful clinical validation of dual incretin receptor agonism. The compound was designed to activate both GLP-1R and GIPR in a single molecule, exploiting a concept that had been debated in academic endocrinology for over a decade: whether adding GIP receptor agonism to GLP-1R agonism would enhance or diminish metabolic outcomes.

The scientific controversy around GIP was significant. Some researchers had proposed that GIP receptor antagonism (blocking the receptor) might be beneficial for weight loss, since GIP was known to promote fat storage in certain contexts. Lilly’s bet on agonism rather than antagonism was validated spectacularly when tirzepatide’s phase 3 SURMOUNT trials showed up to 22.5% body weight reduction — dramatically outperforming semaglutide’s approximately 15% in comparable populations. Tirzepatide received FDA approval as Mounjaro (for diabetes, 2022) and Zepbound (for obesity, 2023).

The compound’s structure is a 39-amino-acid peptide with modifications including a C20 fatty diacid moiety that enables once-weekly dosing by binding to albumin in the bloodstream. Its development code was LY3298176. Tirzepatide proved that the multi-receptor approach was not just theoretically appealing but clinically transformative, directly paving the way for Lilly’s subsequent triple agonist program that produced retatrutide.

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Tesamorelin: Developed for HIV Lipodystrophy at Theratechnologies (2000s)

The origin of tesamorelin lies in the HIV/AIDS epidemic and a specific side effect of antiretroviral therapy that devastated patients’ quality of life. In the late 1990s and early 2000s, as highly active antiretroviral therapy (HAART) transformed HIV from a death sentence into a manageable chronic condition, a new problem emerged: many patients developed severe lipodystrophy — abnormal redistribution of body fat characterized by visceral fat accumulation, facial wasting, and peripheral fat loss.

Theratechnologies, a Canadian biopharmaceutical company based in Montreal, developed tesamorelin as a synthetic analogue of the first 44 amino acids of growth hormone releasing hormone (GHRH), with a trans-3-hexenoic acid modification at the N-terminus to improve stability and potency. The rationale was straightforward: stimulating the body’s own growth hormone production (rather than injecting exogenous GH) could reduce visceral fat while preserving the natural pulsatile GH release pattern and feedback mechanisms.

The foundational science behind GHRH itself dates to 1982, when Roger Guillemin’s laboratory at the Salk Institute (the same lab that earned Guillemin a Nobel Prize for discovering somatostatin and TRH) isolated and characterized GHRH from a pancreatic tumor. This provided the template sequence that Theratechnologies modified to create tesamorelin.

Clinical trials demonstrated that tesamorelin significantly reduced visceral adipose tissue in HIV-associated lipodystrophy without the supraphysiological GH levels and side effects associated with direct GH injection. The FDA approved tesamorelin as Egrifta in 2010, making it one of the few peptides to achieve full regulatory approval. Subsequent research has expanded interest in tesamorelin to cognitive function (GH/IGF-1 signaling plays roles in neuroplasticity) and non-HIV visceral fat reduction.

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MOTS-c: Discovered in the Mitochondrial Genome at USC (2015)

The discovery of MOTS-c in 2015 fundamentally changed how scientists think about mitochondria. For decades, mitochondria were understood primarily as cellular power plants — organelles that produce ATP through oxidative phosphorylation. The discovery that the mitochondrial genome encodes bioactive peptides with systemic signaling functions was a paradigm shift.

MOTS-c was identified by Changhan David Lee’s laboratory at the University of Southern California (USC) Leonard Davis School of Gerontology. Lee’s team was systematically searching the mitochondrial genome’s open reading frames — sections of mitochondrial DNA that could potentially encode small peptides. They identified a 16-amino-acid peptide encoded within the 12S rRNA region of mitochondrial DNA and named it MOTS-c (Mitochondrial Open Reading Frame of the Twelve S rRNA type-c).

The discovery was published in Cell Metabolism in March 2015 and immediately attracted attention because MOTS-c was shown to activate AMPK (AMP-activated protein kinase), the master cellular energy sensor that coordinates metabolic responses to exercise, caloric restriction, and energy stress. In preclinical studies, MOTS-c improved insulin sensitivity, enhanced glucose uptake in skeletal muscle, prevented age-related metabolic decline, and increased exercise capacity — leading to its characterization as an exercise mimetic peptide.

MOTS-c was not the first mitochondrial-derived peptide discovered — that distinction belongs to humanin, identified in 2001. But MOTS-c’s potent metabolic effects and its connection to exercise physiology gave it a unique profile that resonated broadly with the research community. Lee’s subsequent work showed that MOTS-c levels decline with age and that the peptide is released into the bloodstream during exercise, suggesting it functions as a mitochondrial-encoded hormone — a “mitokine” — that communicates the mitochondria’s metabolic status to the rest of the body.

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SS-31 (Elamipretide): Designed by a Cornell Biochemist to Target Mitochondria (2004)

Unlike most peptides on this list, SS-31 was not discovered in nature — it was designed. In the early 2000s, Hazel Szeto, a biochemist at Weill Cornell Medical College in New York, was working on the problem of how to deliver antioxidant molecules directly to mitochondria. The challenge was that most antioxidant compounds could not cross the double membrane of mitochondria in sufficient concentrations to be therapeutically useful.

Szeto and her colleague Peter Bhatt Schiller designed a series of small synthetic tetrapeptides with a specific alternating aromatic-cationic motif (aromatic amino acid – basic amino acid – aromatic amino acid – basic amino acid) that enabled them to concentrate in the inner mitochondrial membrane at concentrations 1,000 to 5,000 times higher than in the surrounding cytoplasm. The series was named “SS” for Szeto-Schiller, and SS-31 (D-Arg-dimethylTyr-Lys-Phe-NH2) emerged as the most promising candidate.

What made SS-31 unique was its mechanism. Rather than simply scavenging free radicals like a conventional antioxidant, SS-31 interacted directly with cardiolipin — a phospholipid found exclusively in the inner mitochondrial membrane that is essential for the structural integrity and function of electron transport chain complexes. By stabilizing cardiolipin, SS-31 optimized electron flow through the respiratory chain, increasing ATP production while reducing the generation of reactive oxygen species at the source.

SS-31 entered clinical development as elamipretide (licensed to Stealth BioTherapeutics, later Epirium Bio), with clinical trials conducted in heart failure, Barth syndrome (a rare genetic disease involving cardiolipin metabolism), age-related macular degeneration, and primary mitochondrial myopathy. It received FDA Fast Track designation for Barth syndrome. The compound’s journey from rational peptide design to clinical trials represents one of the most successful examples of mechanism-based drug development in peptide science.

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Ipamorelin: Developed at Novo Nordisk as a Selective GH Secretagogue (1998)

The origin of ipamorelin traces to the broader effort to develop growth hormone secretagogues (GHS) — compounds that stimulate the body’s own GH production rather than providing exogenous growth hormone. The GHS story begins in 1976 when Cyril Bowers at Tulane University discovered that modified enkephalin peptides could stimulate GH release from pituitary cells. This led to the development of GHRP-6 and GHRP-2, the first generation of GH-releasing peptides.

These early GHRPs had a significant limitation: they stimulated not only GH release but also cortisol, prolactin, and ACTH secretion, and GHRP-6 in particular triggered strong appetite stimulation through ghrelin receptor activation. Researchers at Novo Nordisk set out to create a more selective GH secretagogue that could stimulate growth hormone release without these confounding hormonal effects.

Ipamorelin, a pentapeptide, emerged from this selectivity-focused development program and was first described in publications in 1998. It activates the growth hormone secretagogue receptor (GHS-R, later identified as the ghrelin receptor) but with a selectivity profile that distinguished it from all predecessors: it produces dose-dependent GH release without significant effects on cortisol, prolactin, or ACTH levels. This clean hormonal profile made it the most selective member of the GHRP family and established it as the preferred GH secretagogue for research applications where confounding hormonal changes are undesirable.

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CJC-1295 No DAC: Engineered From GHRH at ConjuChem Biotechnologies (2005)

The development of CJC-1295 originated at ConjuChem Biotechnologies, a Canadian company that specialized in extending the half-life of therapeutic peptides through chemical modification technology. The starting point was human growth hormone releasing hormone (GHRH), the 44-amino-acid hypothalamic peptide first isolated by Roger Guillemin’s group at the Salk Institute in 1982.

Natural GHRH has a half-life of only 5-7 minutes in circulation due to rapid enzymatic degradation by dipeptidyl peptidase-IV (DPP-IV). This extremely short half-life made therapeutic use impractical. ConjuChem’s approach was to modify the first 29 amino acids of GHRH (the minimum fragment retaining full biological activity) with amino acid substitutions at positions 2, 8, 15, and 27 that conferred resistance to DPP-IV degradation.

The “DAC” (Drug Affinity Complex) version of CJC-1295 included a maleimido derivative that bound covalently to serum albumin after injection, extending the half-life to approximately 8 days. The “No DAC” version — also known as Modified GRF (1-29) or Mod GRF — retained the amino acid substitutions for DPP-IV resistance but without the albumin-binding moiety, giving it a half-life of approximately 30 minutes. This shorter-acting version became the preferred research compound because its pulsatile GH release pattern more closely mimics the body’s natural GHRH secretion rhythm, whereas the sustained GH elevation from the DAC version risked receptor desensitization.

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Epitalon: Synthesized at the St. Petersburg Institute of Bioregulation (1980s–2000s)

The story of epitalon (also spelled epithalon or epithalone) begins with Vladimir Khavinson, a gerontologist at the St. Petersburg Institute of Bioregulation and Gerontology in Russia. Beginning in the 1980s, Khavinson developed a theory of “bioregulation” — the idea that short peptides (typically 2-4 amino acids) could regulate gene expression and restore normal cellular function in aging tissues.

Khavinson’s laboratory isolated a natural peptide called epithalamin from the pineal gland of cattle and showed that it could restore melatonin production in aging animals and extend lifespan in multiple species. Epitalon (Ala-Glu-Asp-Gly) was synthesized as a standardized, reproducible version of epithalamin’s active sequence. The synthetic version was easier to produce, characterize, and study than the natural extract.

The pivotal discovery came when Khavinson’s group demonstrated that epitalon could activate telomerase — the enzyme responsible for maintaining telomere length at chromosome ends. Telomere shortening is one of the hallmarks of cellular aging (each cell division erodes telomere length slightly until a critical threshold triggers senescence), and telomerase activation had long been proposed as a potential anti-aging mechanism. Epitalon’s ability to reactivate telomerase in human somatic cells was published in peer-reviewed journals and attracted significant international attention.

In one of the most cited studies, epitalon treatment of elderly human cell cultures resulted in telomere elongation beyond the critical length, allowing cells to continue dividing well past their normal replicative limit. In animal longevity studies conducted over Khavinson’s career spanning decades, various bioregulatory peptides including epitalon were associated with significant lifespan extensions in mice, rats, and fruit flies.

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PT-141 (Bremelanotide): An Accidental Discovery During Tanning Peptide Research (1990s–2000s)

The origin of PT-141 is one of the most unexpected in peptide science — a compound developed to create a sunless tan inadvertently turned out to be a potent activator of sexual desire. The story begins at the University of Arizona in the early 1990s, where researchers Mac Hadley and Victor Hruby were studying melanocortin peptides — a family of hormones derived from proopiomelanocortin (POMC) that regulate skin pigmentation, appetite, and inflammation.

The team developed Melanotan II, a synthetic analogue of alpha-melanocyte-stimulating hormone (α-MSH), as a potential sunless tanning agent that could darken skin without UV exposure — a concept with obvious implications for skin cancer prevention. During clinical testing of Melanotan II, male subjects unexpectedly reported spontaneous erections as a side effect. This was not a vascular response like Viagra — the erections occurred through central nervous system activation, suggesting the melanocortin system played a previously unrecognized role in sexual arousal.

Palatin Technologies, a pharmaceutical company, developed PT-141 (bremelanotide) as a refined version of Melanotan II specifically targeting sexual function. PT-141 is a cyclic heptapeptide that activates melanocortin-4 receptors (MC4R) in the hypothalamus and limbic system — brain regions involved in desire, arousal, and motivation. Unlike PDE5 inhibitors (Viagra, Cialis) that work through peripheral blood flow, PT-141 acts on the brain’s desire circuitry, making it the only compound in its class that addresses sexual desire at the neurological level.

The FDA approved PT-141 as Vyleesi in 2019 for hypoactive sexual desire disorder (HSDD) in premenopausal women — making it the first melanocortin-based therapy approved for sexual dysfunction. Its journey from a tanning experiment to a groundbreaking sexual health treatment is a classic example of how unexpected clinical observations can redirect an entire research program.

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Kisspeptin-10: Discovered Through Cancer Research at Penn State (1996–2001)

The discovery of kisspeptin is a fascinating case of a cancer research finding that revolutionized reproductive endocrinology. In 1996, a team led by Danny Welch at Penn State University College of Medicine was searching for genes that suppress cancer metastasis. They identified a gene on chromosome 1 that, when expressed in melanoma cells, dramatically reduced the cells’ ability to form metastatic colonies. They named it KISS1 — after Hershey’s Kisses, because the research was conducted in Hershey, Pennsylvania (home of the chocolate factory).

The KISS1 gene encoded a peptide initially called “metastin” for its metastasis-suppressing properties. But the transformative discovery came in 2003, when two independent research groups (Seminara et al. at Harvard and de Roux et al. in Paris) identified that mutations in the kisspeptin receptor (GPR54/KISS1R) caused a complete failure of puberty. This meant kisspeptin was not just a cancer-related peptide — it was a master regulator of the entire reproductive hormone cascade.

Subsequent research revealed that kisspeptin neurons in the hypothalamus are the primary upstream trigger for GnRH (gonadotropin-releasing hormone) release, which in turn drives LH and FSH secretion — the hormones controlling testosterone production, ovulation, and fertility. Kisspeptin-10 (the 10-amino-acid C-terminal fragment of kisspeptin-54) retains full biological activity at the receptor and has become the standard research form.

The peptide’s dual origin — discovered through cancer research, repurposed through reproductive genetics — makes it unique in the peptide landscape. From Hershey, Pennsylvania to fertility clinics worldwide, kisspeptin’s journey illustrates how basic science discoveries can have applications that their discoverers never imagined.

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Oxytocin: First Isolated at University College London (1906–1953)

The origin of oxytocin spans nearly half a century of Nobel Prize-winning science. The story begins in 1906, when Sir Henry Dale at University College London observed that extracts from the posterior pituitary gland caused uterine contractions. He named the active substance “oxytocin” from the Greek words for “quick” (oxys) and “birth” (tokos).

For decades, oxytocin remained a crude pituitary extract — researchers knew it existed and what it did, but its precise chemical structure was unknown. The breakthrough came in 1953, when Vincent du Vigneaud at Cornell University determined oxytocin’s complete amino acid sequence (a nine-amino-acid cyclic peptide with a disulfide bridge) and achieved its total chemical synthesis. This was the first peptide hormone ever synthesized in a laboratory — a landmark achievement that earned du Vigneaud the Nobel Prize in Chemistry in 1955.

Oxytocin’s subsequent research history expanded its known functions far beyond childbirth. Successive decades of research revealed roles in lactation (1960s), pair bonding and maternal behavior (1970s–1980s, notably by Thomas Insel and C. Sue Carter studying prairie voles), trust and social cognition (2000s, including Michael Kosfeld’s famous “trust game” experiments), and anxiety modulation (2010s). The discovery that intranasal administration could deliver oxytocin to the central nervous system opened an explosion of behavioral research that continues today.

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NAD+: Discovered in 1906, Resurrected for Aging Research a Century Later

The history of NAD+ (nicotinamide adenine dinucleotide) is one of the longest in all of biochemistry. NAD+ was first discovered in 1906 by Arthur Harden and William John Young at the Lister Institute in London during their studies of yeast fermentation. They observed that a heat-stable, low-molecular-weight fraction of yeast extract was essential for the fermentation process — this fraction contained what would eventually be identified as NAD+. Harden received the Nobel Prize in Chemistry in 1929 for this work.

Hans von Euler-Chelpin determined NAD+’s chemical structure in the 1930s (earning his own Nobel Prize), and over the following decades, NAD+ was recognized as a central coenzyme in cellular metabolism — required for glycolysis, the citric acid cycle, and oxidative phosphorylation. By mid-century, NAD+ biochemistry was considered largely “solved” — a well-understood coenzyme with defined metabolic roles.

The modern renaissance of NAD+ research began in 2000, when Leonard Guarente’s laboratory at MIT discovered that sirtuins — a family of enzymes involved in stress response, DNA repair, and longevity — required NAD+ as a co-substrate. This meant NAD+ was not just a passive metabolic shuttle but an active signaling molecule whose availability directly regulated the activity of genes involved in aging and cellular repair. Subsequent work by David Sinclair at Harvard and others demonstrated that NAD+ levels decline dramatically with age and that restoring NAD+ could rejuvenate mitochondrial function, enhance DNA repair, improve insulin sensitivity, and extend healthspan in animal models.

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N-Acetyl Semax: Developed at the Russian Academy of Sciences (1982–1990s)

The origin of Semax lies in Cold War-era Soviet neuroscience. In the early 1980s, researchers at the Institute of Molecular Genetics of the Russian Academy of Sciences, led by Nikolai Myasoedov, were investigating fragments of ACTH (adrenocorticotropic hormone) for potential nootropic and neuroprotective properties. ACTH is a 39-amino-acid pituitary hormone primarily known for stimulating cortisol release from the adrenal glands, but Soviet researchers had observed that certain ACTH fragments could improve learning and memory in animal models without affecting cortisol.

Myasoedov’s team systematically tested modified versions of the ACTH(4-10) fragment — the seven amino acids that retained cognitive activity without hormonal effects. They added a C-terminal tripeptide (Pro-Gly-Pro) to improve stability and brain penetration, creating the heptapeptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro). The compound was developed through the Soviet military-medical research system and was approved as a pharmaceutical in Russia in 1994 for conditions including cognitive impairment, stroke recovery, and optic nerve atrophy.

N-Acetyl Semax is a further modification with an acetyl group at the N-terminus, which improves resistance to enzymatic degradation and enhances bioavailability. Research on N-Acetyl Semax has demonstrated upregulation of BDNF (brain-derived neurotrophic factor) and NGF (nerve growth factor), enhancement of attention and memory, neuroprotection against ischemic brain injury, and modulation of serotonergic and dopaminergic neurotransmission.

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SLU-PP-332: Designed at Saint Louis University as an Exercise Mimetic (2023)

The origin of SLU-PP-332 represents the newest chapter in peptide and small-molecule research — the deliberate design of compounds that mimic the metabolic effects of exercise. The compound was developed by Thomas Bhatt Burris and his team at Saint Louis University (SLU) and was first published in 2023 in the Journal of Medicinal Chemistry.

Burris’s research focused on estrogen-related receptors (ERRs) — a family of orphan nuclear receptors that regulate mitochondrial biogenesis, fatty acid oxidation, and oxidative phosphorylation in skeletal muscle. ERRα and ERRγ are activated naturally during exercise and are responsible for many of the metabolic adaptations that occur with endurance training — including the shift toward more fatigue-resistant, oxidative muscle fibers.

SLU-PP-332 (named for Saint Louis University, Pharmacological Probe #332) was designed as a selective ERRα/γ agonist that could activate these exercise-related transcription programs without actual physical activity. In preclinical studies, the compound increased exercise capacity in sedentary mice, enhanced fatty acid oxidation, shifted muscle fiber composition toward more oxidative types, and reduced body weight gain in obese models — all hallmarks of endurance training adaptation.

The compound attracted global media attention as an exercise in a pill candidate. Unlike traditional peptides that require injection, SLU-PP-332 is an oral small molecule (capsule form), which broadens its potential research applications and accessibility. Its development reflects a growing trend in metabolic research: using targeted small molecules and peptides to activate specific exercise-related pathways for researchers studying the molecular mechanisms of physical activity’s health benefits.

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What the Origin Stories Tell Us About the Future of Peptide Research

Looking across the complete history of every major research peptide reveals several striking patterns that help predict where the field is heading.

Accidental discoveries drive the field. PT-141 was supposed to be a tanning agent. Kisspeptin was a cancer metastasis gene. BPC-157 was a gastric juice fraction. MOTS-c emerged from searching for hidden genes in mitochondrial DNA. The most transformative peptides were not designed to do what they ended up being studied for. This pattern suggests that the next groundbreaking research peptide may come from an equally unexpected source.

Multi-receptor targeting is accelerating. The trajectory from single-target semaglutide to dual-target tirzepatide to triple-target retatrutide to the 2026 quintuple agonist shows a clear trend toward increasingly complex, multi-mechanism compounds. Each generation builds on the previous one, and the conjugation chemistry that enables these advances is becoming a platform technology applicable far beyond weight loss.

Rational design is catching up to natural discovery. The earliest peptides (BPC-157, TB-500, GHK-Cu, oxytocin) were all discovered in nature. The middle generation (ipamorelin, CJC-1295, Semax) involved targeted modifications of natural sequences. The newest compounds (SS-31, SLU-PP-332) were designed from scratch based on mechanistic understanding. As computational tools and AI-powered drug design improve, the balance is shifting from “find it in nature” to “design it for a purpose.”

Old compounds keep finding new applications. NAD+ was discovered in 1906 but didn’t become relevant to aging research until 2000. Oxytocin was characterized in the 1950s but its social neuroscience applications weren’t explored until the 2000s. GHK-Cu was isolated in 1973 but its gene-regulatory activity wasn’t discovered until the 2010s. This suggests that existing research peptides likely have applications that have not yet been identified.

Explore our complete catalog of research-grade peptides — each with its own remarkable origin story and ongoing scientific legacy — at praxpeptides.com/shop.

All compounds discussed in this article are intended strictly for in-vitro research and laboratory use only. They are not intended for human consumption, veterinary use, or any clinical application. Researchers are responsible for ensuring compliance with all applicable regulations in their jurisdiction.