Peptide Database
265 therapeutic peptides with research summaries, clinical findings, and regulatory status.
Ziconotide (Prialt)
A synthetic 25-amino acid peptide identical to omega-conotoxin MVIIA, a neurotoxin found in the venom of the marine cone snail Conus magus. Ziconotide selectively and reversibly blocks N-type voltage-gated calcium channels (Cav2.2) in the dorsal horn of the spinal cord, inhibiting neurotransmitter release from primary afferent nociceptive neurons. It provides analgesia without opioid receptor activation, tolerance development, or respiratory depression.
Difelikefalin (Korsuva)
A selective kappa-opioid receptor (KOR) agonist peptide that does not cross the blood-brain barrier, providing peripheral analgesia and anti-pruritic effects without central opioid side effects such as euphoria, dysphoria, sedation, or addiction. Difelikefalin activates kappa receptors on peripheral sensory neurons and immune cells to reduce itch signaling and inflammation. Its restricted CNS penetration is a deliberate design feature to avoid abuse potential.
ARA-290
A synthetic 11-amino acid peptide derived from the structure of erythropoietin (EPO) that selectively activates the innate repair receptor (IRR), a heteromer of the EPO receptor and the beta common receptor (CD131). Unlike EPO, ARA-290 does not stimulate erythropoiesis or promote thrombosis. It produces cytoprotective, anti-inflammatory, and tissue-reparative effects by activating the IRR on neurons, immune cells, and endothelial cells.
Palmitoylethanolamide (PEA)
An endogenous fatty acid amide belonging to the N-acylethanolamine family, naturally produced by cells in response to tissue damage and inflammation. PEA acts primarily through peroxisome proliferator-activated receptor alpha (PPAR-alpha), downregulating mast cell activation and pro-inflammatory mediator release. It also modulates the endocannabinoid system via the entourage effect, enhancing anandamide activity at CB1/CB2 receptors and TRPV1 channels without directly binding cannabinoid receptors.
Dynorphin A
Dynorphin A is an endogenous opioid peptide of 17 amino acids that preferentially binds to and activates kappa-opioid receptors, though it also has affinity for mu and delta receptors at higher concentrations. It is derived from the precursor protein prodynorphin and plays a complex role in pain modulation, stress responses, and dysphoria. Unlike mu-opioid agonists, kappa receptor activation can produce analgesia without typical euphoria but may induce aversive psychological effects. Dynorphin also has non-opioid actions at high concentrations, including NMDA receptor modulation.
Leu-Enkephalin
Leu-enkephalin is a pentapeptide (Tyr-Gly-Gly-Phe-Leu) that functions as an endogenous opioid agonist with preferential activity at delta-opioid receptors and moderate affinity for mu receptors. It is derived from the precursor proenkephalin and is widely distributed in the central and peripheral nervous systems. The peptide modulates nociceptive transmission and contributes to endogenous analgesia. Leu-enkephalin is rapidly degraded by peptidases, limiting its duration of action.
Met-Enkephalin
Met-enkephalin is a pentapeptide (Tyr-Gly-Gly-Phe-Met) that differs from leu-enkephalin only in its C-terminal amino acid. It acts as an endogenous opioid with preferential delta-opioid receptor activity and also binds mu-opioid receptors. Derived from proenkephalin, met-enkephalin is involved in pain modulation, stress responses, and immune regulation. Like other enkephalins, it is subject to rapid enzymatic degradation by aminopeptidases and enkephalinases.
Endomorphin-1
Endomorphin-1 is a tetrapeptide (Tyr-Pro-Trp-Phe) that exhibits highly selective agonist activity at the mu-opioid receptor, the primary target for analgesic opioids. It is one of two endomorphin isoforms and represents the most selective endogenous mu-opioid ligand identified to date. Endomorphin-1 is distributed in pain-processing regions of the central nervous system. Its selective mu receptor activity theoretically offers potent analgesia with a potentially different side effect profile compared to less selective opioids.
Endomorphin-2
Endomorphin-2 is a tetrapeptide (Tyr-Pro-Phe-Phe) that, like endomorphin-1, demonstrates highly selective agonism at mu-opioid receptors. The two endomorphins differ by a single amino acid but share similar receptor selectivity and analgesic properties. Endomorphin-2 is found in spinal and supraspinal sites involved in nociception. Its unique selectivity profile has generated interest in developing analogs that retain efficacy while minimizing respiratory depression and other opioid side effects.
Nociceptin / Orphanin FQ
Nociceptin, also known as orphanin FQ, is a 17-amino acid peptide that acts as the endogenous ligand for the nociceptin/orphanin FQ peptide (NOP) receptor, a member of the opioid receptor family with distinct pharmacology. Despite structural similarity to dynorphin A, nociceptin does not bind classical opioid receptors. Its effects on pain are complex and context-dependent, producing analgesia at the spinal level but pronociceptive or hyperalgesic effects at supraspinal sites. The peptide also modulates stress, anxiety, and reward pathways.
Conantokin-G
Conantokin-G is a 17-amino acid peptide originally isolated from the venom of the cone snail Conus geographus. It acts as a selective antagonist of N-methyl-D-aspartate (NMDA) receptors containing the NR2B subunit, which are implicated in chronic pain, neuropathic pain, and central sensitization. The peptide contains gamma-carboxyglutamic acid residues that are critical for its activity and metal ion binding. Conantokin-G represents a novel class of non-opioid analgesics targeting glutamatergic neurotransmission.
Dermorphin
Dermorphin is a heptapeptide opioid agonist originally isolated from the skin of South American Phyllomedusa frogs. It exhibits high selectivity and affinity for the mu-opioid receptor, with potency approximately 30 to 40 times greater than morphine in animal models. The unique D-alanine residue at position 2 confers resistance to peptidase degradation and contributes to its prolonged analgesic activity. Its potent receptor binding has made it a valuable research tool for studying opioid receptor pharmacology.
Deltorphin
Deltorphin is a heptapeptide opioid agonist also derived from Phyllomedusa frog skin secretions, characterized by high selectivity for delta-opioid receptors. Like dermorphin, it contains an unusual D-amino acid residue that enhances metabolic stability and receptor affinity. Deltorphin exhibits analgesic properties distinct from mu-opioid agonists, with reduced respiratory depression and addiction liability in animal models. It has served as a pharmacological tool to elucidate delta-opioid receptor physiology and potential therapeutic roles.
Neuropeptide FF
Neuropeptide FF (NPFF) is an octapeptide belonging to the RFamide family, characterized by an arginine-phenylalanine-amide motif at the C-terminus. It acts on two G protein-coupled receptors, NPFF1 and NPFF2, and modulates opioid-induced analgesia, tolerance, and hyperalgesia. NPFF is widely distributed in the central nervous system and participates in pain modulation, opioid tolerance mechanisms, and cardiovascular regulation. Its dual role as both a pronociceptive and anti-opioid peptide has generated interest in targeting its receptors for chronic pain management.