Immune

ARA-290 (international nonproprietary name: cibinetide) is a synthetic 11-amino acid peptide derived from the tissue-protective domain of erythropoietin (EPO). It was deliberately engineered to preserve EPO's non-hematopoietic, tissue-protective signaling while completely eliminating erythropoietic activity. The N-terminal pyroglutamate (pGlu) modification confers enzymatic stability and contributes to receptor specificity. The compound has been most extensively studied for sarcoidosis-associated small fiber neuropathy (SFN), with two published randomized controlled trials in humans. It is investigational only — not approved by the FDA or EMA for any indication — and is available exclusively through clinical trials.

Crystagen is a synthetic tripeptide Glu-Asp-Pro (EDP), which is the primary active fraction of Thymalin — a heterogeneous polypeptide extract derived from calf thymus. It acts as an immune-modulating bioregulator, functioning as part of the KNDy-equivalent system for immune regulation in the Khavinson bioregulator framework. **Vendor mislabeling warning:** Many research peptide vendors incorrectly label Crystagen as an "eye" or "vision/lens" peptide. This is factually incorrect. Crystagen (EDP) is an immune/thymus bioregulator. The eye-related peptide in Khavinson's bioregulator system is Retinalamin (also called Visoluten or Retinalamin complex) — a distinct compound from bovine retinal tissue. Crystagen has no published evidence for ophthalmic applications.

Glutathione (GSH) is a tripeptide composed of glutamate, cysteine, and glycine, linked by an unusual gamma peptide bond between the gamma-carboxyl group of glutamate and the amino group of cysteine. It is the most abundant non-protein thiol in mammalian cells, with intracellular concentrations ranging from 1-10 mM. Present in virtually every cell in the body, it functions as the principal intracellular antioxidant and plays critical roles in detoxification, immune function, and cellular homeostasis. Unlike most peptides discussed in research databases, glutathione is an endogenous compound with well-established biochemistry. Its clinical relevance stems from the observation that glutathione levels decline with age and are depleted in numerous disease states including HIV/AIDS, liver disease, neurodegenerative disorders, and pulmonary conditions. Exogenous supplementation strategies — including direct administration, precursor supplementation (NAC), and liposomal delivery — are areas of active clinical investigation.

KPV (Lys-Pro-Val) is a naturally occurring tripeptide corresponding to the C-terminal fragment (residues 11-13) of alpha-melanocyte-stimulating hormone (α-MSH). Despite being only three amino acids, KPV retains the potent anti-inflammatory activity of the full 13-amino acid α-MSH peptide while lacking its melanogenic (tanning) and hormonal effects. This dissociation of anti-inflammatory activity from melanocortin receptor-mediated effects makes KPV an attractive candidate for inflammatory conditions where pigmentation changes would be an unwanted side effect. KPV has been studied primarily in the context of intestinal inflammation and skin disorders, with preclinical data showing efficacy in colitis models and dermatitis. Its small molecular size (342 Da) offers practical advantages — oral bioavailability, skin penetration, and low manufacturing cost relative to larger peptides. The peptide is part of a broader research effort to identify the minimal active fragments of endogenous anti-inflammatory peptides for therapeutic development.

LL-37 is the sole cathelicidin antimicrobial peptide in humans, produced primarily in neutrophils, mast cells, epithelial cells, and macrophages. It is generated by proteolytic cleavage of the hCAP18 (18 kDa) precursor protein by proteinase 3 or elastase. The designation "LL-37" refers to the two N-terminal leucines and the 37-amino acid length of the mature peptide. LL-37 is a constitutive component of innate immunity, acting as a first-responder defense against a broad spectrum of pathogens while simultaneously orchestrating inflammatory, wound-healing, and tissue-regenerative responses. The peptide is endogenously expressed and regulated by immune activation, hypoxia, and vitamin D signaling — the latter making it a mechanistic link between vitamin D status and infection susceptibility. Its expression is notably deficient in chronic venous leg ulcers, providing rationale for topical therapeutic applications.

PNC-27 is a synthetic 32-amino acid chimeric peptide designed as a targeted anticancer agent. It consists of two functional domains: an N-terminal sequence corresponding to amino acids 12-26 of the HDM-2 (MDM2) binding domain of the p53 tumor suppressor protein, fused to a C-terminal membrane-residency peptide (MRP) derived from the penetratin sequence of Drosophila antennapedia homeodomain. The fusion of a p53-mimetic HDM-2 binding domain with a membrane-inserting sequence creates a compound that selectively targets and kills cancer cells through a membrane-based, p53-independent mechanism. PNC-27 has no published human clinical trials. All efficacy data is from in vitro cell culture experiments and ex vivo studies of patient-derived tumor cells. It is a research compound available through peptide vendors with no regulatory approval.

Thymalin (Russian brand: Timalin) is a heterogeneous polypeptide extract from calf thymus gland, containing a complex mixture of peptides with molecular weights between 1,000 and 10,000 Da. It is an approved pharmaceutical in Russia for immune deficiency states. Its active fractions have been identified and synthesized as distinct short peptides: Crystagen (EDP tripeptide), Vilon (KE dipeptide), and Thymogen (EW dipeptide) — all studied individually by Khavinson's group. Thymalin occupies an unusual position in the peptide research landscape: it has human observational data from a 6–8 year study of 266 elderly patients that is exceptional in scope for this class of compound, while simultaneously lacking the randomized controlled trial design that Western regulatory bodies require. It is not approved by the FDA or EMA. In Western research peptide markets, Thymalin is sold as a lyophilized powder with limited standardization. Molecular weight and formula fields are not applicable — Thymalin is a complex polypeptide mixture, not a single defined compound.

Thymosin Alpha-1 (Tα1) is a 28-amino acid peptide originally isolated from thymic tissue (Thymosin Fraction 5) by Allan Goldstein at George Washington University in the 1970s. It is an N-terminally acetylated peptide that plays a central role in T-cell maturation and immune system regulation. The synthetic form, marketed as thymalfasin (Zadaxin), is approved in over 35 countries for the treatment of chronic hepatitis B and as an immune adjuvant, though it does not have FDA approval in the United States. Tα1 occupies a distinctive position in peptide therapeutics as one of the few immunomodulatory peptides with extensive clinical trial data and regulatory approval in multiple jurisdictions. It has been studied in over 4,400 patients across clinical trials for hepatitis B, hepatitis C, certain cancers, HIV/AIDS, and vaccine enhancement in immunocompromised populations. Its mechanism of action involves enhancement of innate and adaptive immunity through dendritic cell maturation and T-cell differentiation, while simultaneously promoting immune tolerance through separate regulatory pathways.

Thymulin (originally named Facteur Thymique Sérique, or Serum Thymic Factor) is a nonapeptide exclusively produced by thymic epithelial cells, discovered by Jean-François Bach at the Hôpital Necker in Paris in the 1970s. It is unique among thymic peptides in its absolute requirement for zinc — the apo-peptide (without zinc) is biologically inactive, and only the zinc-coordinated form can bind to its receptor and exert immunomodulatory effects. The zinc ion is coordinated by the asparagine, serine, and glutamine residues in the C-terminal portion of the molecule. Thymulin levels in circulation decline dramatically with age, paralleling the involution of the thymus gland. Peak levels occur during puberty and decrease to near-undetectable concentrations by age 60. This decline correlates with the age-related deterioration of T-cell-mediated immunity (immunosenescence), making thymulin a biomarker of thymic function and a candidate therapeutic for restoring immune competence in aging. Its zinc dependency also connects thymulin biology to the well-documented effects of zinc deficiency on immune function.

Vasoactive Intestinal Peptide (VIP) is an endogenous 28-amino acid neuropeptide belonging to the secretin/glucagon superfamily, produced throughout the central and peripheral nervous systems, immune cells, and gastrointestinal tract. It was initially characterized as a vasodilator and gastrointestinal motility regulator but has since been established as a pleiotropic signaling molecule with potent immunomodulatory, neuroprotective, and autonomic regulatory functions. VIP signals through three G protein-coupled receptors: VPAC1 (expressed in brain, lung, liver, lymphocytes), VPAC2 (expressed in brain, pancreas, smooth muscle, mast cells), and PAC1 (primarily targeted by PACAP). The wide distribution of these receptors explains VIP's diverse physiological and pathological roles. VIP is an investigational agent with no FDA approval for any therapeutic use; its short plasma half-life (~1-2 minutes) and broad receptor distribution have historically limited clinical development.