Description

Retatrutide (LY3437943) is a lipidated 39-amino-acid peptide that activates three receptors in one molecule: GIP, GLP-1 and glucagon. The fatty-acid side chain binds albumin, which gives it a long half-life. It is one of the most closely followed metabolic peptides in current research.

Overview of published research

The discovery paper described retatrutide's balanced activity at all three receptors and reported weight loss and improved glucose control in obese mice, together with early clinical pharmacology [1].

In diet-induced obese male rats, daily retatrutide combined with cagrilintide reduced body weight and food intake more than either compound alone, and improved cholesterol, triglycerides and insulin [2]. In mouse and hamster models of fatty liver disease, retatrutide improved several metabolic and liver markers [3].

References

1. Coskun T, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Cell Metab. 2022. PMID 35985340
2. Petersen J, et al. Cagrilintide and retatrutide combination therapy enhances weight loss and metabolic outcomes in obese male rats. Nat Metab. 2026. PMID 42744908
3. Briand F, et al. Retatrutide Shows Multiple Metabolic Benefits in Diet-Induced Obese MASH Mouse and Hamster Models. Obesity (Silver Spring). 2026. PMID 41741376

Description

GHK-Cu is the copper(II) complex of the tripeptide glycyl-L-histidyl-L-lysine, first isolated from human plasma. GHK binds copper with high affinity, and the complex has been studied for four decades in models of connective-tissue formation and wound repair.

Overview of published research

In a rat wound-chamber model, injections of GHK-Cu increased the accumulation of new connective tissue, including collagen and glycosaminoglycans, compared with saline [1]. A follow-up study in the same model found that GHK-Cu changed the glycosaminoglycan and small-proteoglycan make-up of the healing tissue [2].

Not every model shows an effect: in irradiated rat skin flaps, a topical GHK-Cu gel applied for 10 days made no measurable difference to flap ischaemia, blood-vessel count or VEGF expression [3].

References

1. Maquart FX, et al. In vivo stimulation of connective tissue accumulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ in rat experimental wounds. J Clin Invest. 1993. PMID 8227353
2. Siméon A, et al. Expression of glycosaminoglycans and small proteoglycans in wounds: modulation by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu(2+). J Invest Dermatol. 2000. PMID 11121126
3. Parker NP, et al. Effects of topical copper tripeptide complex on wound healing in an irradiated rat model. Otolaryngol Head Neck Surg. 2013. PMID 23744835

Description

Melanotan II (MT-II) is a cyclic heptapeptide analogue of α-melanocyte-stimulating hormone (α-MSH). The ring structure makes it far more stable than the native hormone, and it activates several melanocortin receptors (MC1R, MC3R, MC4R), which makes it a standard tool for studying the melanocortin system.

Overview of published research

Given centrally to rats, MT-II reduced food intake and also changed drinking, body temperature and activity [1]. Given peripherally, it produced a marked drop in food intake, and the study mapped which brain regions were activated [2].

In rats made obese by a high-fat diet, six days of MT-II infusion reduced body weight and visceral fat and increased thermogenesis, even though melanocortin receptor expression in these animals was reduced [3].

References

1. Murphy B, et al. Centrally administered MTII affects feeding, drinking, temperature, and activity in the Sprague-Dawley rat. J Appl Physiol. 2000. PMID 10904062
2. Trivedi P, et al. Exploring the site of anorectic action of peripherally administered synthetic melanocortin peptide MT-II in rats. Brain Res. 2003. PMID 12834882
3. Li G, et al. Unabated anorexic and enhanced thermogenic responses to melanotan II in diet-induced obese rats despite reduced melanocortin 3 and 4 receptor expression. J Endocrinol. 2004. PMID 15225137

Description

Ipamorelin is a synthetic pentapeptide (Aib-His-D-2Nal-D-Phe-Lys-NH₂) that acts on the ghrelin receptor (GHS-R1a). It was described as the first selective growth-hormone secretagogue: it releases growth hormone without the parallel rise in ACTH and cortisol seen with earlier compounds of its class.

Overview of published research

In rat pituitary cells and in anaesthetised rats, ipamorelin released growth hormone with a potency comparable to GHRP-6, while leaving ACTH and cortisol levels largely unaffected [1].

In young rats, ipamorelin increased the longitudinal bone growth rate in a dose-dependent way [2]. In adult female rats given ipamorelin for 12 weeks, bone mineral content rose, driven mainly by larger bone cross-sections rather than denser bone [3].

References

1. Raun K, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998. PMID 9849822
2. Johansen PB, et al. Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth Horm IGF Res. 1999. PMID 10373343
3. Svensson J, et al. The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats. J Endocrinol. 2000. PMID 10828840

Description

Semax is a synthetic heptapeptide (Met-Glu-His-Phe-Pro-Gly-Pro): the ACTH(4-7) fragment of adrenocorticotropic hormone extended with a Pro-Gly-Pro tail that protects it from rapid breakdown. It has no hormonal activity of its own and is studied mainly for its effects on neurotrophins in the brain.

Overview of published research

In rats, Semax bound specifically in the basal forebrain and raised levels of brain-derived neurotrophic factor (BDNF) protein there [1]. A single intranasal dose also increased BDNF and TrkB expression in the rat hippocampus [2].

After experimental cerebral ischaemia in rats, Semax activated the transcription of neurotrophin genes and their receptor genes [3].

References

1. Dolotov OV, et al. Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. J Neurochem. 2006. PMID 16635254
2. Dolotov OV, et al. Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus. Brain Res. 2006. PMID 16996037
3. Dmitrieva VG, et al. Semax and Pro-Gly-Pro activate the transcription of neurotrophins and their receptor genes after cerebral ischemia. Cell Mol Neurobiol. 2010. PMID 19633950

Description

BPC-157 is a synthetic 15-amino-acid peptide (GEPPPGKPADDAGLV) derived from a sequence of a protein found in gastric juice. It is stable in solution and is one of the most widely studied peptides in experimental models of tendon, ligament and soft-tissue repair.

Overview of published research

In rats with a surgically transected Achilles tendon, BPC-157 improved healing across biomechanical, functional and microscopic measures, and in cell culture it stimulated the growth of tendon cells [1].

When the Achilles tendon was detached from the bone, BPC-157 promoted tendon-to-bone healing in rats and counteracted the slower healing seen with a corticosteroid [2]. Follow-up work on rat tendon fibroblasts linked the effect to increased cell outgrowth, survival under oxidative stress and cell migration [3].

References

1. Staresinic M, et al. Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendocytes growth. J Orthop Res. 2003. PMID 14554208
2. Krivic A, et al. Achilles detachment in rat and stable gastric pentadecapeptide BPC 157: Promoted tendon-to-bone healing and opposed corticosteroid aggravation. J Orthop Res. 2006. PMID 16583442
3. Chang CH, et al. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration. J Appl Physiol. 2011. PMID 21030672