Peptides Studied for Immune Function

Octreotide is a synthetic 8-amino-acid cyclic peptide (MW ~1019.2 g/mol) that mimics the pharmacological actions of natural somatostatin but with a significantly longer half-life. It was the first somatostatin analog approved by the FDA (1988) and is available as both an immediate-release subcutaneous injection (Sandostatin) and a long-acting intramuscular depot formulation (Sandostatin LAR). Octreotide is FDA-approved for acromegaly, severe diarrhea associated with carcinoid tumors, and VIPomas (vasoactive intestinal peptide-secreting tumors).

Lanreotide is a synthetic 8-amino-acid cyclic somatostatin analog (MW ~1096.3 g/mol) available as a long-acting deep subcutaneous depot injection (Somatuline Depot/Autogel). It is FDA-approved for acromegaly and for the treatment of unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Lanreotide self-assembles into nanotubes at high concentration, enabling sustained drug release over 4 weeks from a single injection.

Romiplostim is a peptide-Fc fusion protein (peptibody) with a molecular weight of approximately 59,000 g/mol that acts as a thrombopoietin (TPO) receptor agonist. It was FDA-approved in August 2008 (Nplate) for the treatment of chronic immune thrombocytopenia (ITP) in adults with an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Romiplostim consists of an IgG1 Fc domain fused to a peptide sequence that binds and activates the TPO receptor (c-Mpl) on megakaryocytes, stimulating platelet production.

Enfuvirtide is a 36-amino-acid synthetic peptide (MW ~4492 g/mol) that inhibits HIV-1 entry into host cells by blocking the fusion of viral and cellular membranes. It was FDA-approved in March 2003 (Fuzeon), making it the first HIV fusion inhibitor approved for clinical use. Enfuvirtide is indicated for treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy, and is administered as a twice-daily subcutaneous injection.

Icatibant is a synthetic 10-amino-acid peptidomimetic (MW ~1304.5 g/mol) that acts as a selective, competitive antagonist of the bradykinin B2 receptor. It was FDA-approved in August 2011 (Firazyr) for the treatment of acute attacks of hereditary angioedema (HAE) in adults. Icatibant contains five non-natural amino acids that confer resistance to enzymatic degradation and selectivity for the B2 receptor, and is self-administered as a subcutaneous injection.

Thymosin beta-4 (Tβ4) is a naturally occurring 43-amino acid protein found in virtually all human and animal cells. It is the most abundant member of the beta-thymosin family and plays fundamental roles in cell migration, wound healing, and tissue repair. Tβ4 is distinct from TB-500, which is a synthetic peptide containing only the active heptapeptide region (Ac-LKKTETQ) of Tβ4. The full-length protein is being developed as RGN-259 (RegeneRx Biopharmaceuticals) eye drops for dry eye, neurotrophic keratopathy, and other ophthalmic conditions, with multiple Phase II/III clinical trials completed or ongoing.

Larazotide (AT-1001) is a synthetic 8-amino acid peptide that acts as a tight junction regulator. It is being developed as an oral adjunct therapy for celiac disease, designed to reduce intestinal permeability ("leaky gut") triggered by gluten exposure. It is the first drug in its class and has completed Phase II clinical trials and a Phase III trial (INN-202, also called CeDLara). Larazotide works locally in the gut lumen without significant systemic absorption. It was originally developed by Alba Therapeutics and later acquired by Innovate Biopharmaceuticals (now 9 Meters Biopharma).

Substance P is an 11-amino-acid neuropeptide (sequence: Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2, MW ~1347.6 g/mol) belonging to the tachykinin family. It is widely distributed in the central and peripheral nervous systems, where it functions as a neurotransmitter and neuromodulator involved in pain transmission, inflammation, and emesis. Substance P is the primary endogenous agonist of the neurokinin-1 receptor (NK1R) and is the pharmacological target of the antiemetic drug aprepitant (Emend).

Vasoactive Intestinal Peptide (VIP) is a 28-amino-acid neuropeptide (MW ~3326.8 g/mol) widely distributed in the central and peripheral nervous systems, lungs, and gastrointestinal tract. It is a potent vasodilator, bronchodilator, and immunomodulator. The synthetic form aviptadil (RLF-100) was investigated for COVID-19-associated acute respiratory distress syndrome (ARDS) and has been studied in pulmonary arterial hypertension. VIP is also used diagnostically in VIPoma identification.

Bradykinin is a 9-amino-acid vasoactive peptide (sequence: Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg, MW ~1060.2 g/mol) generated by the kallikrein-kinin system through proteolytic cleavage of high-molecular-weight kininogen by plasma kallikrein. It is a potent endogenous vasodilator, pain mediator, and inflammatory agent with no approved therapeutic use as an exogenous drug. It is the primary target of ACE inhibitor-mediated cough and angioedema.

Glutathione is a tripeptide (Glu-Cys-Gly, MW ~307.3 g/mol) and the most abundant intracellular antioxidant in mammalian cells. It is critical for Phase II detoxification, free radical scavenging, immune function, and cellular redox homeostasis. Injectable (SC/IV) glutathione bypasses the poor oral bioavailability (~3%) issue and achieves clinically meaningful plasma levels. It has been studied for conditions ranging from non-alcoholic fatty liver disease to Parkinson disease.

BPC-157 is a synthetic 15-amino-acid peptide (sequence: Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val, MW ~1419.5 g/mol) derived from a protein found in human gastric juice. It has demonstrated robust regenerative and cytoprotective effects across hundreds of animal studies spanning tendon, ligament, muscle, bone, nerve, GI tract, and blood vessel healing. However, human clinical data is extremely limited — only three pilot studies have examined BPC-157 in humans as of 2025 (knee pain n=16, interstitial cystitis n=12, IV safety n=2). The FDA classifies it as Category 2, prohibiting compounding, and WADA bans its use in sports.

Thymosin alpha-1 (Ta1) is a clinically proven, 28-amino-acid peptide (MW ~3,108 g/mol, Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-Asp-Leu-Lys-Glu-Lys-Lys-Glu-Val-Val-Glu-Glu-Ala-Glu-Asn-OH) naturally produced by the thymus gland. A synthetic version (thymalfasin, marketed as Zadaxin) is approved in over 35 countries for treating hepatitis B and C and as an immune adjuvant. It modulates rather than simply boosts immunity, making it unique among immune therapies. Clinical trials involving thousands of patients show robust safety data, with an FDA orphan drug designation for hepatitis B in the US. A 2024 study showed potential in restoring T-cell counts in immunological non-responder HIV patients.

ARA-290 (cibinetide) is a synthetic 11-amino-acid peptide (MW ~1257 g/mol) derived from the helix B surface of erythropoietin (EPO). Unlike recombinant EPO, ARA-290 does not bind the classical EPO receptor homodimer and therefore does not stimulate erythropoiesis (red blood cell production), avoiding the thrombotic and cardiovascular risks of EPO. Instead, it selectively activates the innate repair receptor (IRR), a heterodimer of EPOR and β-common receptor (CD131), expressed on tissues undergoing stress or damage. ARA-290 received FDA Orphan Drug Designation for treatment of sarcoidosis-associated small fiber neuropathy. Multiple Phase II clinical trials have been completed demonstrating improvements in neuropathic pain, autonomic function, and corneal nerve fiber regeneration.

Pemvidutide (ALT-801) is a dual GLP-1/glucagon receptor agonist being developed by Altimmune for the treatment of obesity and nonalcoholic steatohepatitis (NASH/MASH). It is a once-weekly injectable peptide designed to combine GLP-1-mediated appetite suppression with glucagon-mediated increases in energy expenditure and hepatic fat reduction. Phase II trials (MOMENTUM and IMPACT) have been completed, showing promising weight loss and liver fat reduction. Phase III development is anticipated.

Cotadutide (MEDI0382) is a dual GLP-1/glucagon receptor agonist developed by AstraZeneca (originally MedImmune). It is a once-daily injectable peptide designed to combine GLP-1 receptor-mediated glucose lowering and appetite suppression with glucagon receptor-mediated hepatic fat oxidation and energy expenditure. Phase II trials have been completed in type 2 diabetes, obesity, and NASH/MASH. Development status is uncertain after mixed Phase II results and AstraZeneca portfolio prioritization.

Thymulin (FTS) is a 9-amino-acid zinc metallopeptide (sequence: pyroGlu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn, MW ~858 g/mol) secreted exclusively by thymic epithelial cells. It requires zinc binding for biological activity and plays a central role in T-cell differentiation and maturation. Thymulin serum levels decline with age and thymic involution, and it has been investigated as an immunomodulator in immunodeficiency states and aging.

Pexiganan (MSI-78) is a 22-amino-acid synthetic analog of magainin 2, an antimicrobial peptide originally isolated from the skin of the African clawed frog (Xenopus laevis). It has broad-spectrum bactericidal activity and was developed as a topical cream (Locilex) for infected diabetic foot ulcers. Despite reaching Phase III clinical trials, pexiganan was not approved by the FDA, which determined it was not superior to existing treatments.

Omiganan (MBI 226) is a 12-amino-acid synthetic cationic antimicrobial peptide (sequence: ILRWPWWPWRRK-NH2, MW ~1779 g/mol) derived from indolicidin, a natural antimicrobial peptide from bovine neutrophils. It has been investigated in Phase III clinical trials for prevention of catheter-related infections and topical treatment of rosacea (as CLS001), but has not received regulatory approval for either indication.

Brilacidin (PMX-30063) is a synthetic small-molecule defensin-mimetic (MW ~564 g/mol) developed by Innovation Pharmaceuticals (formerly Cellceutix). It is a peptidomimetic, not a true peptide, designed to mimic the amphipathic structure and antimicrobial mechanism of host defense peptides (defensins). Brilacidin has been investigated in Phase II clinical trials for acute bacterial skin and skin structure infections (ABSSSI) and oral mucositis, and was explored for COVID-19.