methionine enkephalin (STAT-401) / Biostax Corp, Statera BioPharma - LARVOL DELTA

Synthesis, Structure-Activity Studies, and Therapeutic Potential of Met-enkephalin Derivatives. (PubMed, Curr Top Med Chem) - "We highlight OGF and its derivatives in anticancer, analgesic, and immunomodulatory studies, and the potential for use in the treatment of other diseases, such as neurodegenerative (Alzheimer's, Parkinson's), diabetes, and viral diseases. The therapeutic potential of OGF is very large; therefore, it can be expected that the synthesis of new analogues and conjugates with used chemotherapeutic agents will be continued."

Journal • Alzheimer's Disease • CNS Disorders • Diabetes • Infectious Disease • Metabolic Disorders • Movement Disorders • Oncology • Pain • Parkinson's Disease

Heat and cold stresses exert disparate effects on expression of proenkephalin, and concentrations of Met-enkephalin in the hypothalamus, pituitary and adrenal glands, plasma concentrations Met-enkephalin, Leu-enkephalin, β-endorphin and corticosterone and opioid receptor binding in chickens. (PubMed, Poult Sci) - "Heat and, to a less extent, cold stressed pullets had decreased concentrations of Met-enkephalin in hypothalamic, anterior pituitary and adrenal tissues but increased concentrations of total Met-enkephalin (enzymically released) and proenkephalin (PENK) expression. There were also effects of heat- or cold- stress on delta (Δ), kappa (K) and mu (M) opioid receptor binding in the hypothalamus, anterior pituitary and adrenal glands."

Journal • PENK

Simulation of peptide retention on dual reversed phase: strong cation exchange functionalized stationary phase gradients. (PubMed, J Chromatogr A) - "Experimental retention data for four representative peptides (valine-tyrosine-valine, methionine enkephalin, leucine enkephalin, and angiotensin II) were collected using uniform C4 and strong cation exchange columns to establish accurate fit parameters for the linear solvent strength and ionic exchange models, respectively. For the conditions tested, the resulting analysis confirmed that a resolution of 2.5 for all critical pairs could be achieved within 15 min across various gradient combinations. The resulting simulations indicate a strong potential for utilizing small, strategic segments of functionalization on stationary phase gradients to significantly enhance separations using traditional mobile phase gradients."

Journal

Mucins and neuromodulators involved in mucus secretion in the alimentary canal of Siluriformes. (PubMed, Tissue Cell) - "In addition, an immunohistochemical protocol was used employing 5 antibodies against molecules involved in mucus secretion, namely choline acetyltransferase, serotonin, galanin, and leu- and met-enkephalin...The significant differences observed in the sugar residues between the two species could be related to their specific feeding ecology, carnivorous for S. glanis and omnivorous for A. melas. The presence of plant polysaccharides in the black bullhead diet needs more complex mucosal components than the wels catfish diet which involves reduced fermentative processes."

Journal • CHAT • GAL

Enteric neurons modulate colorectal cancer cell cycle through a PCSK1 - Methionine-Enkephalin Axis. (PubMed, bioRxiv) - "Effects of dexamethasone and liraglutide on PCSK1 expression in ENS-containing murine tissue were evaluated. These findings define a previously unrecognized ENS-derived neuro-oncologic pathway that is associated with reduced CRC cell proliferation and identify the GR/GLP1R-PCSK1-M-ENK axis as a potentially actionable therapeutic node. This study identifies a neuronal PCSK1 - M-ENK pathway in the ENS that directly suppresses colorectal cancer growth through local OGFr activation, revealing a previously unrecognized neuropeptidergic mechanism of tumor control within the intestinal microenvironment."

Journal • Addiction (Opioid and Alcohol) • Colorectal Cancer • Oncology • Solid Tumor • KRAS • PCSK1 • PENK

Immunohistochemical Staining of the Brain of the Tuatara Sphenodon punctatus. (PubMed, Brain Behav Evol) - "These markers include leucine-enkephalin, the preproenkephalin-derived neuropeptide methionine-enkephalin-arg-phe, the preproenkephalin-derived neuropeptide peptide E, substance P, tyrosine hydroxylase, LANT6, neuropeptide Y, glutamic acid decarboxylase, serotonin, vasoactive intestinal polypeptide, luteinizing hormone releasing hormone, and cholecystokinin-8. To show its value, we provide here an overview of the labeling obtained with each antibody, highlighting forebrain and midbrain, which shows remarkable resemblance to that reported in turtles. Images of the labeling will be made available at Brainmaps.org, and the slides will be banked at the Museum of Comparative Zoology at Harvard University, where they can be analyzed in greater depth by interested investigators."

Journal • PENK

Endogenous opioid peptides in trichotillomania: An exploratory analysis of focused and automatic hair-pulling subtypes. (PubMed, Psychoneuroendocrinology) - "These findings provide the first evidence of reduced peripheral endogenous opioid levels in TTM and suggest subtype-specific differences in opioid system functioning. Alterations in endogenous opioids may be associated with reward- and stress-related mechanisms underlying hair-pulling behavior, particularly in the focused subtype. Further longitudinal and multimodal studies are warranted to clarify the role of opioid signaling in TTM."

Journal • Behavior Disorders • Mental Retardation • Mood Disorders • Psychiatry

Unraveling the role of iodide in photosensitized oxidation of Met-Enkephalin. (PubMed, J Photochem Photobiol B) - "Stable products resulting from the oxidation of MetEnk by 33CB* complements previous works on MetEnk irradiations, showing formation of products on Met and Tyr side chains (CBH-adducts to Met and diTyr). The presence of iodide anions protected the MetEnk from oxidation due to competitive quenching of 33CB* and no new products have been identified as the action of iodide anions."

Journal

Neutrophil Formyl Peptide Receptor-1 Activation Triggers Endogenous Opioid Release for Local, Non-addictive Analgesia (IMMUNOLOGY 2026) - "Among these mediators, endogenous opioid peptides (e.g., Met-enkephalin) can provide potent peripheral analgesia without central nervous system toxicity... Small-molecule activation of neutrophil FPR1 can elicit endogenous opioid peptide secretion, revealing a neuroimmune pathway for site-specific analgesia. By leveraging innate immune trafficking and secretory programs, this approach may enable peripherally acting, opioid-mediated pain relief while minimizing systemic adverse effects, motivating in vivo efficacy and safety studies."

Addiction (Opioid and Alcohol) • CNS Disorders • Depression

Editorial: Lifetime achievements in avian physiology. (PubMed, Front Physiol) - No abstract available

Journal

Enkephalin Gates D2-MSN Disinhibition of the Ventral Pallidum During Cocaine Abstinence. (PubMed, bioRxiv) - "Application of exogenous met-enkephalin inhibited GABA release in D2-PenkKO slices but not in cocaine-abstinent controls, because GABA release was already suppressed in control mice...Our findings identify D2-MSNs as the source and enkephalin as the opioid responsible for this striatal circuit plasticity. More broadly, this suggests a synaptic mechanism by which synthetic opioids may potentiate cocaine seeking and promote opioid-cocaine polysubstance use."

Journal • DRD2 • PENK

Mechanistic insights into the therapeutic properties of delta opioid receptor. (PubMed, Sci Adv) - "The endogenous agonist, met-enkephalin, not only stabilizes the active-state conformation but also catalyzes transitions between the active and inactive states. These results reveal how ligand-specific interactions and receptor dynamics can govern pharmacological profiles and provide a framework for developing DOR-targeted therapeutics."

Journal • CNS Disorders • Depression • Mood Disorders • Pain • Psychiatry

Met-enkephalin and other opioid peptides in the stress response of chickens: lessons from laboratory animals and livestock. (PubMed, Front Physiol) - No abstract available

Journal • PENK

Discovery and dynamic pharmacology of µ-opioid receptor positive allosteric modulators. (PubMed, bioRxiv) - "Opioid agonists such as morphine and fentanyl exert analgesic effects by binding and activating the µ-opioid receptor (µOR), yet agonism of the µOR causes a slate of serious side effects...The most effective of these compounds enhanced the activity of all orthosteric opioid agonists tested, including the native opioid peptide met-enkephalin...To that end, we used single-molecule fluorescence resonance energy transfer experiments to detail the impact that our novel µOR PAM has on the dynamic activation behavior of a key region on the intracellular face of the receptor. Our results here provide both a new chemical scaffold that acts as a µOR PAM and detailed pharmacological and dynamic insights into its mechanism of action."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Pain • Psychiatry

Met-enkephalin modulates the stress responses of plasma concentrations of corticosterone, delta opioid receptor binding, pro-enkephalin expression, and processing in chickens. (PubMed, Front Physiol) - "There were negative relationships between plasma concentrations of corticosterone and Met-enkephalin and between those of native Met-enkephalin and total Met-enkephalin. The ability of Met-enkephalin to attenuate the stress response of corticosterone, and probably other glucocorticoids, is novel and opens up several new lines of inquiry, including its site of action and its source."

Journal • PENK

Peptide chirality and opioid receptor modulation: Hepatoprotective effect of d-Met-enkephalin in acetaminophen-induced liver injury. (PubMed, Acta Pharm) - "l-Met-enkephalin is a neuropeptide known to exert protective effects in various experimental models of autoimmune and inflammatory diseases. This preservation of biological activity may be attributed to the presence of the achiral amino acid glycine at positions 2 and 3, which maintains the functional conformation of the d-enantiomer. The role of opioid receptor involvement was further examined through direct receptor blockade using naltrexone and indirect inhibition with the antisense peptide IPPKY."

Journal • Addiction (Opioid and Alcohol) • Hepatology • Immunology • Inflammation • Liver Failure

Methionine enkephalin upregulates toll-like receptors in macrophages to suppress severe fever with thrombocytopenia syndrome virus infection. (PubMed, Front Immunol) - "Compared with the TLR7 agonist imiquimod (IMQ), MENK demonstrated a greater advantage in modulating macrophages to resist SFTSV infection. MENK upregulated the expression levels of the pattern recognition receptors and cytokine receptors; promoted the nuclear transcription to modulate cellular immune responses; and increased the levels of the cytokines to induce inflammatory responses against SFTSV infection. Notably, MENK possessed unique advantages and exhibited efficacy comparable to IMQ in restoring antiviral immunity, suggested that MENK emerged as a promising host-directed therapeutic candidate or vaccine prototype against SFTSV infection, warranting further preclinical and clinical investigation."

IO biomarker • Journal • Hematological Disorders • Infectious Disease • Inflammation • Thrombocytopenia • CXCL10 • IL17A • IL17RA • IL1B • TLR3 • TLR8 • TLR9 • TNFA

Metabolic Shifts Induced by Treatment with Statin Influences Circulating Concentrations of the Stress Hormone, Cortisol, but Has Different Effects on Selected Cytokines, Adipokines and Neuropeptides in Lean and Fat Lines of Young Pigs. (PubMed, Metabolites) - "There were also decreases in the plasma concentrations of visfatin, cortisol, Met-enkephalin and endothelin-1...Statin treatment was associated with increased concentrations of TNFα in epicardial adipose tissue and of IL-6 in visceral adipose tissue in both lean and fat breeds of pigs. It is concluded that statins cause shifts in the expression and/or concentrations of both adipokines and inflammatory cytokines in adipose tissue."

Journal • Oncology • EDN1 • IL6 • LEP • NAMPT • PENK • RETN • TNFA

Extracellular processing of proopiomelanocortin generates short beta endorphin that regulates rat keratinocytes via the delta opioid receptor. (PubMed, Sci Rep) - "Functional assays showed β-END(1-9) reduced cAMP levels via DOR signaling, acting as a full agonist with about half the potency of methionine-enkephalin...Differential gene expression analysis revealed modulation of genes involved in collagen maturation and hyaluronic acid synthesis, suggesting roles in skin barrier function. Collectively, these findings suggest that POMC is processed into β-END(1-9) in atopic-inflammatory skin, and this peptide acts via DOR expressed in keratinocytes to promote the expression of skin-protective factors."

Journal • Preclinical • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • POMC-null Obesity • Pruritus

Metabolic syndrome reduces but does not eliminate the cardioprotective effect of adaptation to hypoxia: the link with changes in the opioid system. (PubMed, Pflugers Arch) - "Endomorphin-2, β-endorphin, dynorphin A (1-13), and met-enkephalin content in myocardial tissue was increased in response to CCH...A correlation was identified between plasma and myocardial tissue opioid peptide levels and the extent of myocardial injury, as well as between myocardial opioid peptide content and contractility. Furthermore, CCH and MS caused a reduction in the expression of δ- (DOR) and κ- (KOR) opioid receptors, and also an increase in µ- (MOR) opioid receptor expression. These findings suggest that a decrease in opioid peptide content could impair adaptive cardioprotection in MS."

Journal • Cardiovascular • Coronary Artery Disease • Metabolic Disorders • Myocardial Ischemia • Reperfusion Injury

The Involvement of the Peptidergic Systems in Breast Cancer Development. (PubMed, Cancers (Basel)) - "Breast cancer cells overexpress peptide receptors; at the same time they are known to interact with peptides that (a) exert an oncogenic action (adrenomedullin 2, endothelin, gastrin-releasing peptide, neurokinin A, neuromedin, neuropeptide Y, neurotensin, substance P, vasoactive intestinal peptide), (b) exert an anticancer action (angiotensin (1-7), ghrelin, peptide YY) or (c) exert dual oncogenic and anticancer effects (adrenomedullin, angiotensin II, bradykinin, corticotropin-releasing factor, β-endorphin, glucagon-like peptide 1, gonadotropin-releasing hormone, kisspeptin, methionine-enkephalin, oxytocin)...Future lines of research are suggested in breast cancer using promising anti-breast-cancer peptide receptor antagonists (HOE-140, exendin (9-39), bosentan, macitentan, PD168,368, CGP71,683A, SR48,692, aprepitant) or agonists (FR190,997, semaglutide, exendin 4, goserelin) mentioned in this review...Taken together, the available data highlight the enormous promise..."

Journal • Review • Breast Cancer • Oncology • Solid Tumor • GRP-10

Constructing Generalized Sample Transition Probabilities with Biased Simulations. (PubMed, J Chem Theory Comput) - "The proposed algorithm is validated on model systems such as a harmonic oscillator, Müller-Brown potential system, alanine dipeptide in vacuum, and met-enkephalin in solvent. The results demonstrate that GSTP effectively recovers the unbiased eigenvalues and eigenstates from the biased data. GSTP provides a general framework for analyzing kinetic information in complex systems, where biased simulations are necessary to access longer time scales."

Journal

Mechanism(s)-of-Action for Arginine Therapy in Children with Sickle Cell Disease and Vaso-Occlusive Pain: Results of a Pharmacokinetics/Pharmacodynamics Study (ASH 2023) - "Its nociceptive effects are through induction of Met-enkephalins release in the brain... A total of 13 patients (age 13±3 years, 56% male, 88% Hb-SS, 85% on hydroxyurea) were enrolled... IV Arg therapy increased plasma arginine concentration 2-5 times above baseline at presentation for VOE, and GABR also increased as expected in this pharmacokinetics study with both reaching a maximum concentration within 1 hour of infusion initiation in all dosing schemes. IV Arg supplementation increases plasma NOx levels suggesting a role for vasodilation as a potential mechanism-of-action during SCD-VOE. Exhaled NO also increased significantly, consistent with previous reports."

Clinical • PK/PD data • Genetic Disorders • Hematological Disorders • Musculoskeletal Pain • Pain • Sickle Cell Disease

Unveiling Dopamine and Met-Enkephalin Dynamics: Simultaneous Co-Detection in Rat Striatum. (PubMed, Anal Chem) - "Finally, a series of experiments combined solid-phase extraction with liquid-chromatography mass spectrometry to independently verify ENK release. The findings provide direct evidence to support widely held assumptions regarding neuropeptide release, and they demonstrate how different classes of signaling molecules can potentially affect distinct cellular populations in striatum─even when released at the same site."

Journal • Preclinical • Addiction (Opioid and Alcohol) • Pain • PENK

Effects of two structurally diverse positive allosteric modulators on signaling bias at the μ-opioid receptor. (PubMed, Mol Pharmacol) - "We determined the potency and efficacy of 6 orthosteric agonists (DAMGO, fentanyl, methadone, morphine, Met-enkephalin, and SR17018) with and without BMS-986187 or BMS-986122, and determined bias factors for the agonists themselves and in the presence of a modulator. SIGNIFICANCE STATEMENT: Biased agonism and positive allosteric modulation at the μ-opioid receptor have been suggested as approaches to improve the therapeutic index of opioid agonists. This work shows how allosteric modulation alters the bias signaling profile of μ-opioid agonists."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Pain • Psychiatry