RPEP-02507 · 2014The bioimplant consisting of polycaprolactone scaffold filled with PuraMatrix peptide hydrogel and seeded with adipose tissue-derived progenitor cells successfully integrated with injured myocardium in mice. Bioluminescence tracking showed de novo and progressive increases in cardiac-specific promoter expression, indicating stem cell differentiation toward cardiac lineages. Functional blood vessels traversed the myocardium-implant interface. Echocardiography revealed a detectable positive effect on cardiac function compared to controls.
Soler-Botija, Carolina; Bagó, Juli R; Llucià-Valldeperas, Aida; Vallés-Lluch, Ana; Castells-Sala, Cristina; Martínez-Ramos, Cristina; Fernández-Muiños, Teresa; Chachques, Juan Carlos; Pradas, Manuel Monleón; Semino, Carlos E; Bayes-Genis, Antoni ·
RPEP-02517 · 2014In this substudy of the SENIORS trial examining 106 elderly heart failure patients, nebivolol did not produce statistically significant changes in natriuretic peptides (NT-proBNP, pro-ANP), cytokines (TNF-α, sFas, sFas-L), or nitric oxide markers (ADMA, SDMA, arginine, citrulline) compared to placebo over 12 months.
However, left ventricular ejection fraction improved significantly in the nebivolol group (from 35% to 43%) compared to placebo (35% to 34%, P=0.01). NT-proBNP showed a non-significant trend toward increase in the nebivolol group (P=0.08), while soluble Fas trended upward in the placebo group (P=0.08).
Taneja, Anil K; Gaze, David; Coats, Andrew J S; Dumitrascu, Dan; Spinarova, Lenka; Collinson, Paul; Roughton, Michael; Flather, Marcus D · Randomized Controlled Trial
RPEP-02518 · 2014Neuropeptide Y (NPY) acting through Y1 receptors in the spinal cord inhibits the release of substance P, a key pain-signaling molecule. This anti-pain effect was significantly enhanced during inflammation — Y1 receptor signaling increased after inflammatory injury, with higher receptor-G protein coupling affinity in inflamed animals compared to uninjured controls.
Specifically, NPY decreased capsaicin-evoked substance P release in spinal cord microdialysate and reduced NK1 receptor internalization (a marker of substance P release) triggered by non-painful stimulation after carrageenan-induced inflammation. After complete Freund's adjuvant (CFA) inflammation, a Y1-selective agonist reduced pain-evoked NK1R internalization in inflamed rats but not in uninjured controls, indicating that inflammation itself enhances the pain-inhibitory capacity of the NPY-Y1 system.
Taylor, B K; Fu, W; Kuphal, K E; Stiller, C-O; Winter, M K; Chen, W; Corder, G F; Urban, J H; McCarson, K E; Marvizon, J C · Animal Study
RPEP-02520 · 2014Anti-doping laboratories have developed multiple analytical methods to detect a wide range of peptide drugs in athlete samples. These include chromatographic-mass spectrometric, electrophoretic, immunological, and combined approaches capable of identifying peptides across all molecular sizes.
Low-molecular-weight peptides detected include growth hormone-releasing peptides (GHRPs), ARA-290, TB-500, AOD-9604, CJC-1295, desmopressin, LH-releasing hormones, and synacthen. Intermediate-sized peptides include insulins, IGF-1 and analogs, mechano growth factor, growth hormone, hCG, and erythropoietin. Larger peptides like stamulumab can also be detected.
However, a significant gap remained between what was technically possible in research settings and what could be reliably implemented in routine daily testing of athlete samples.
Thevis, Mario; Thomas, Andreas; Schänzer, Wilhelm · Review
RPEP-02531 · 2014Fulvestrant (FUL) vs placebo in postmenopausal women produced paradoxical mixed effects:
Estrogen-like actions: Fasting GH increased from 0.096 to 0.23 μg/L (p=0.033), IGFBP-3 increased from 3.6 to 4.0 mg/L (p=0.041). FUL potentiated GH responses to L-arginine/saline (p=0.007), L-arginine/ghrelin (p=0.008), and L-arginine/GHRH+ghrelin (p=0.031), but not L-arginine/GHRH alone.
Anti-estrogen actions: Prolactin decreased from 7.1 to 5.5 μg/L (p=0.05), IGFBP-1 decreased from 44 to 27 μg/L (p=0.048).
Neutral effects: Testosterone, estradiol, estrone, SHBG, IGF-I, LH, and FSH were unaffected.
Veldhuis, Johannes D; Yang, Rebecca J; Wigham, Jean R; Erickson, Dana; Miles, John C; Bowers, Cyril Y ·
RPEP-02535 · 2014A functionalized self-assembling peptide nanofiber scaffold containing link protein N-terminal peptide (link N) significantly promoted bone marrow stem cell (BMSC) adhesion and stimulated the production of type II collagen and aggrecan — the two key structural molecules of cartilage-like tissue found in spinal discs.
The functionalized scaffold (LN-NS, built on the RADA16 self-assembling peptide platform) outperformed the plain RADA16 scaffold in cell adhesion and cartilage matrix production, though it did not increase BMSC proliferation. This suggests the link N peptide directs stem cells toward a cartilage-producing phenotype (chondrogenesis) rather than simply making them multiply faster.
Wang, Baichuan; Sun, Caixia; Shao, Zengwu; Yang, Shuhua; Che, Biao; Wu, Qiang; Liu, Jianxiang · In Vitro
RPEP-02536 · 2014The researchers used NMR temperature coefficients to rapidly identify exposed amide bonds in cyclic peptides — the spots most vulnerable to water and therefore most in need of protection. By selectively N-methylating these positions, they created peptides with improved membrane permeability.
Five leucine-rich peptide scaffolds were tested with various N-methylation patterns. The most promising derivative (peptide 15) achieved 33% oral bioavailability in a rat model, validated through in vivo testing. The approach was further validated by explaining the known oral bioavailability of a somatostatin analog. Membrane permeability was confirmed using both parallel artificial membrane permeability assay (PAMPA) and Caco-2 cell assays before moving to animal testing.
Wang, Conan K; Northfield, Susan E; Colless, Barbara; Chaousis, Stephanie; Hamernig, Ingrid; Lohman, Rink-Jan; Nielsen, Daniel S; Schroeder, Christina I; Liras, Spiros; Price, David A; Fairlie, David P; Craik, David J ·
RPEP-02544 · 2014Nociceptive free-nerve endings and substance P-staining nerve fibers were identified in multiple joint structures: accessory ligaments, synovium (joint lining), subchondral bone (bone beneath cartilage), menisci, and periosteum (bone covering). Calcitonin gene-related peptide (CGRP) was also present in these tissues.
The vasculature may contribute to pain through vasospasm or ischemia, though this mechanism remains unproven. Joint denervation procedures can relieve pain — confirming that articular nerves carry pain signals — but cannot pinpoint the specific tissue source. The review concludes that the primary anatomical source of OA pain remains unclear and likely varies between patients and joints.
Witt, Kevin L; Vilensky, Joel A ·
RPEP-02548 · 2014Among five treatment groups, mice receiving the combination of dexamethasone (DXM) and thymosin alpha-1 (Tα1) timed to dendritic cell number changes had the highest survival rate. Tα1 increased dendritic cell numbers in vivo while DXM reduced them — when combined in a timed approach, they normalized DC numbers during endotoxemia. The combination therapy decreased bacterial translocation to extra-intestinal organs and enhanced clearance of secondary infections. Neither drug alone significantly changed DC capacity to activate T cells or expression of MHCII/CD86.
Xiang, Xiao-song; Li, Ning; Zhao, Yun-zhao; Li, Qiu-rong; Li, Jie-shou ·
RPEP-02558 · 2014The 99mTc-peptide-ZHER2:342 molecular probe was successfully synthesized and labeled with technetium-99m at 98.10 ± 1.73% efficiency. The probe remained highly stable in vitro and showed clear selective imaging: HER2-expressing SKOV-3 tumor xenografts showed high uptake and were clearly visible, while HER2-low MDA-MB-231 xenografts were not detectable at any time point after injection.
The predominant clearance pathway was renal (through the kidneys), which is favorable for imaging because it reduces background signal in the abdomen and allows cleaner tumor visualization.
Zhang, J-M; Zhao, X-M; Wang, S-J; Ren, X-C; Wang, N; Han, J-Y; Jia, L-Z ·
RPEP-02565 · 2014Clinical development of three melanocortin receptor (MCR) agonist peptides has advanced understanding of how the melanocortin pathway regulates sexual function. Melanotan I, melanotan II, and bremelanotide have been studied for treating erectile dysfunction in males and sexual arousal and orgasmic disorders in females.
Unlike phosphodiesterase-5 inhibitors (e.g., sildenafil/Viagra) that act peripherally on nitric oxide/cyclic GMP signaling in genital smooth muscle, MCR agonists target central nervous system pathways involved in mediating arousal and orgasm. The available data support the role of melanocortin pathway activation in regulating both male and female sexual functions, warranting further clinical investigation.
Ückert, Stefan; Bannowsky, Andreas; Albrecht, Knut; Kuczyk, Markus A ·
RPEP-02571 · 2015When TNBS-induced colitis (a model for Crohn's disease) was triggered in VIP knockout mice, they showed a milder clinical profile compared to wild-type mice. Serum levels of TNF-α and IL-6 were lower in VIP-deficient mice. However, colon histopathological scores and local cytokine levels did not differ between the groups, indicating that VIP's absence selectively disrupted certain but not all immunological compartments.
Interestingly, splenocytes from TNBS-treated VIP knockout mice showed enhanced proliferative responses to T cell stimulation (anti-CD3/CD28), suggesting that while some immune functions were dampened, T cell reactivity was actually increased. This pattern — reduced clinical disease but enhanced T cell responses — mirrors findings in VIP knockout mice with endotoxemia and autoimmune encephalomyelitis.
Abad, Catalina; Cheung-Lau, Gardenia; Coûté-Monvoisin, Anne-Claire; Waschek, James A · Animal Study
RPEP-02579 · 2015In a rigorous head-to-head comparison, oxyntomodulin, GLP-1, glucagon, and GLP-1+glucagon combined all reduced food intake by similar amounts compared to saline (roughly 15-17% reduction). However, combining GLP-1 and glucagon together did not produce an additive effect — the combination was no better than either peptide alone.
The mechanisms differed: oxyntomodulin, GLP-1, and GLP-1+glucagon slowed gastric emptying and reduced appetite scores, while glucagon reduced food intake without affecting either gastric emptying or appetite. No peptide infusion significantly changed resting energy expenditure compared to saline.
Bagger, Jonatan Ising; Holst, Jens Juul; Hartmann, Bolette; Andersen, Birgitte; Knop, Filip Krag; Vilsbøll, Tina · Clinical Trial
RPEP-02582 · 2015The review demonstrates that the endogenous opioid system — operating through mu, delta, and kappa receptors activated by peptide ligands (enkephalins, endorphins, and dynorphins) — and the endocannabinoid system share extensive overlap in brain reward circuitry. Both receptor families are G protein-coupled and expressed throughout reinforcement pathways.
Genetic knockout studies in mice have been instrumental in dissecting the specific roles of each receptor and ligand in reward processing. The evidence points to significant functional interactions between these two systems, meaning manipulating one system can alter the other's effects on reward-related behavior.
Befort, Katia ·
RPEP-02583 · 2015Blocking ghrelin receptors (GHS-R1a) in the rat brain with the peptide antagonist d-Lys-3-GHRP-6 impaired memory encoding in a dose-dependent manner. Post-training injection significantly decreased step-through latency, increased time spent in the dark compartment, and increased the number of entries into the dark compartment — all indicating impaired memory consolidation.
Pre-training injection also impaired memory acquisition, significantly increasing time in the dark compartment in a dose-dependent manner. These results demonstrate that ghrelin receptor signaling in the brain is involved in both the acquisition and consolidation stages of memory formation.
Beheshti, Siamak; Shahrokhi, Shahrzad · Animal
RPEP-02585 · 2015The ELIXA trial enrolled 6,068 patients with type 2 diabetes and recent acute coronary syndrome across 49 countries to evaluate whether the GLP-1 receptor agonist peptide lixisenatide affects cardiovascular outcomes. This paper reports the study design and baseline characteristics: participants had a mean age of 60.3 years, mean BMI of 30.2, and average diabetes duration of 9.3 years. The qualifying event was myocardial infarction in 83% and unstable angina in 17%.
ELIXA was the first major cardiovascular outcomes trial of a GLP-1 receptor agonist, designed to evaluate both safety and potential cardiovascular benefit in a high-risk diabetic population.
Bentley-Lewis, Rhonda; Aguilar, David; Riddle, Matthew C; Claggett, Brian; Diaz, Rafael; Dickstein, Kenneth; Gerstein, Hertzel C; Johnston, Peter; Køber, Lars V; Lawson, Francesca; Lewis, Eldrin F; Maggioni, Aldo P; McMurray, John J V; Ping, Lin; Probstfield, Jeffrey L; Solomon, Scott D; Tardif, Jean-Claude; Wu, Yujun; Pfeffer, Marc A · Rct
RPEP-02587 · 2015Palaeolithic-type meals (fish and plant-rich, high in fibre and phytonutrients) dramatically increased GLP-1 and PYY satiety hormones over 180 minutes compared to a WHO guideline reference meal (p=0.001 and p<0.001 respectively). Satiety scores were correspondingly higher. Surprisingly, these effects occurred even when the Palaeolithic meal was matched for energy, protein, fat, and carbohydrates with the reference meal — suggesting the food composition itself, not just macronutrient ratios, drives the gut hormone response.
GIP (another incretin hormone) was significantly suppressed by the Palaeolithic meals. Blood glucose and insulin responses did not differ between meal types.
Bligh, H Frances J; Godsland, Ian F; Frost, Gary; Hunter, Karl J; Murray, Peter; MacAulay, Katrina; Hyliands, Della; Talbot, Duncan C S; Casey, John; Mulder, Theo P J; Berry, Mark J · Rct
RPEP-02591 · 2015Substance P, a neuropeptide concentrated in specific brain compartments called striosomes, has opposite effects on dopamine release depending on exactly where in the striatum you look. In the center of striosomes, substance P boosted dopamine release. At striosome-matrix borders, it suppressed dopamine. In the surrounding matrix, it had no effect.
This bidirectional modulation creates a "center-surround contrast" pattern — substance P sharpens the dopamine signal by enhancing it in one location while suppressing it nearby. The effects were mediated through neurokinin-1 (NK1) receptors. This resolves a long-standing contradiction in the literature, where different studies reported substance P either increasing or decreasing dopamine, depending on where they happened to record.
Brimblecombe, Katherine R; Cragg, Stephanie J · Basic Science (Ex Vivo Electrophysiology)
RPEP-02596 · 2015Both pGHRH-R (pituitary-type GHRH receptor) and its splice variant SV1 were found to be expressed in normal thyroid and papillary thyroid cancer (PTC) cells. Treatment with the GHRH antagonist MIA-602 reduced MMP-2 activity (a marker of tumor invasion capacity) in cancer cells compared to vehicle-treated controls, while normal thyroid cells showed no change in MMP-2 activity.
Interestingly, MIA-602 increased expression of SV1 and pGHRH-R in tumor cells, which may alter signaling kinase sensitivity. However, the treatment did not affect cell proliferation rates in either tumor or normal cells, indicating anti-invasion rather than anti-proliferation activity in this setting.
Catanuto, Paola; Tashiro, Jun; Rick, Ferenc G; Sanchez, Patricia; Solorzano, Carmen C; Glassberg, Marilyn K; Block, Norman L; Lew, John I; Elliot, Sharon J; Schally, Andrew V ·
RPEP-02598 · 2015Pasireotide, a multi-receptor somatostatin analog peptide with high affinity for SST receptor 5, normalized urinary free cortisol levels in up to 28% of patients with Cushing's disease at doses of 600-1,200 μg twice daily after 3 months. Combining pasireotide with cabergoline increased the normalization rate to 50%, and adding ketoconazole achieved biochemical control in most patients. Treatment improved blood pressure, weight, lipid profile, and quality of life. Hyperglycemia is the main side effect, caused by pasireotide's suppression of insulin and GLP-1 secretion.
Ceccato, Filippo; Scaroni, Carla; Boscaro, Marco ·
RPEP-02601 · 2015Researchers created α/β-peptide foldamers based on a stapled Bim BH3 peptide that could enter cells and block intracellular protein-protein interactions involved in apoptotic signaling — matching the function of the parent stapled α-peptide. Crucially, the α/β-peptide was nearly 100-fold more resistant to proteolytic degradation than the parent stapled α-peptide. This demonstrates that combining backbone modification (α/β substitution) with side chain cross-linking (stapling) produces synergistic benefits for peptide drug design.
Checco, James W; Lee, Erinna F; Evangelista, Marco; Sleebs, Nerida J; Rogers, Kelly; Pettikiriarachchi, Anne; Kershaw, Nadia J; Eddinger, Geoffrey A; Belair, David G; Wilson, Julia L; Eller, Chelcie H; Raines, Ronald T; Murphy, William L; Smith, Brian J; Gellman, Samuel H; Fairlie, W Douglas ·
RPEP-02604 · 2015Thirty days of Peptide 6 treatment (50 nmol/day) in mice with controlled cortical impact TBI produced multiple beneficial effects:
- 80% increase in newborn neurons in the dentate gyrus (hippocampus), specifically mature neurons rather than uncommitted progenitors
- Prevention of neuronal loss in the CA1 region and parietal cortex
- Reversal of TBI-induced dendritic and synaptic density loss
- Increased activity in tri-synaptic hippocampal circuitry
- Improved memory recall on behavioral testing
TBI mice also showed increases in Alzheimer-type hyperphosphorylated tau and amyloid-beta, linking TBI pathology to Alzheimer's disease mechanisms. Peptide 6 addressed both the TBI damage and these Alzheimer-associated biomarkers.
Chohan, Muhammad Omar; Bragina, Olga; Kazim, Syed Faraz; Statom, Gloria; Baazaoui, Narjes; Bragin, Denis; Iqbal, Khalid; Nemoto, Edwin; Yonas, Howard ·
RPEP-02610 · 2015Researchers developed a general synthetic strategy for creating high-affinity peptide ligands that target specific epitopes on protein biomarkers. The method uses synthetic epitope fragments with click chemistry-compatible groups that self-select the best binding peptide from a library. The approach successfully generated epitope-targeted linear and macrocyclic peptide ligands against 12 different diagnostic or therapeutic protein targets, producing small molecule alternatives to monoclonal antibodies.
Das, Samir; Nag, Arundhati; Liang, JingXin; Bunck, David N; Umeda, Aiko; Farrow, Blake; Coppock, Matthew B; Sarkes, Deborah A; Finch, Amethist S; Agnew, Heather D; Pitram, Suresh; Lai, Bert; Yu, Mary Beth; Museth, A Katrine; Deyle, Kaycie M; Lepe, Bianca; Rodriguez-Rivera, Frances P; McCarthy, Amy; Alvarez-Villalonga, Belen; Chen, Ann; Heath, John; Stratis-Cullum, Dimitra N; Heath, James R ·
RPEP-02613 · 2015Researchers designed stapled peptides based on the Cullin3 protein that successfully mimicked the protein-protein interaction between Cul3 and BTB domain-containing proteins. The stapled peptides adopted the correct helical structure (confirmed by CD and NMR), bound to BTB domains of KCTD11 (tetrameric) and KCTD5 (pentameric) with high affinity (~300-600 nM), and showed increased serum stability compared to unstapled peptides. The binding affinity was comparable to that of the full-length Cul3 protein with its natural BTB partners.
de Paola, Ivan; Pirone, Luciano; Palmieri, Maddalena; Balasco, Nicole; Esposito, Luciana; Russo, Luigi; Mazzà, Daniela; Di Marcotullio, Lucia; Di Gaetano, Sonia; Malgieri, Gaetano; Vitagliano, Luigi; Pedone, Emilia; Zaccaro, Laura ·
RPEP-02616 · 2015The chapter covers several computational strategies for cyclic peptide drug design:
- Virtual screening of cyclic peptide libraries can exploit their constrained shape, which is more predictable than flexible linear peptides
- Cyclic peptides, while not traditionally 'druglike' by standard rules, may achieve membrane permeability and proteolytic resistance — overcoming the two main barriers to oral peptide delivery
- Computational approaches include: diverse combinatorial virtual library generation, incorporation of various cyclization strategies and structural modifications, evolutionary algorithms for screening large libraries, machine learning approaches, and bioinformatics-guided library design
- The constrained conformation of cyclic peptides makes them more amenable to structure-based virtual screening than linear peptides
Duffy, Fergal J; Devocelle, Marc; Shields, Denis C ·
RPEP-02617 · 2015Intranasal oxytocin (24 IU) administered after Pavlovian fear conditioning facilitated fear extinction in healthy men. Using fMRI, researchers showed that oxytocin simultaneously dampened amygdala activity (the brain's fear center) while boosting prefrontal cortex signaling (the region responsible for rational control over fear). This dual action matches exactly what neuroscience models predict would be needed to overcome conditioned fear responses.
Specifically, in the early phase of extinction, oxytocin increased skin conductance responses and prefrontal cortex activation to conditioned fear stimuli. In the late phase, oxytocin enhanced the decline of fear responses. The amygdala suppression was present in both phases, suggesting a sustained calming effect on the brain's alarm system.
Eckstein, Monika; Becker, Benjamin; Scheele, Dirk; Scholz, Claudia; Preckel, Katrin; Schlaepfer, Thomas E; Grinevich, Valery; Kendrick, Keith M; Maier, Wolfgang; Hurlemann, René · Randomized Controlled Trial
RPEP-02618 · 2015Dulaglutide demonstrated efficacy across multiple clinical scenarios: as first-line, second-line, and third-line therapy for type 2 diabetes. Key benefits included reductions in HbA1c, fasting plasma glucose, and postprandial glucose levels, along with weight loss.
Additional benefits included improved β-cell function and cardiovascular risk factor improvements (lower blood pressure, improved lipid levels). The drug had a low hypoglycemia risk and an adverse effect profile similar to other GLP-1 RAs, primarily transient gastrointestinal symptoms with a potential risk for pancreatitis.
Edwards, Krystal L; Minze, Molly G ·
RPEP-02624 · 2015In vitro models using human liver microsomes and S9 fractions successfully generated detectable metabolites for all seven peptide hormones tested: desmopressin, TB-500, GHRP-2, GHRP-6, hexarelin, LHRH, and leuprolide. Both endopeptidase and exopeptidase activity was observed across all models.
Comparison between liver and kidney tissue models showed no significant differences in metabolite profiles. Deamidation was not observed in any of the standard models but could be induced using α-chymotrypsin. The authors concluded these in vitro systems are practical tools for forensic and clinical detection of peptide metabolites in biological fluids.
Esposito, Simone; Deventer, Koen; Geldof, Lore; Van Eenoo, Peter ·
RPEP-02630 · 2015The monomeric peptide triagonist demonstrated supraphysiological potency with equally balanced activity at GLP-1, GIP, and glucagon receptors, without cross-reactivity at other related receptors. It proved superior to the best available dual coagonists and monoagonists at reducing body weight, enhancing glycemic control, and reversing hepatic steatosis in rodent models of obesity. Genetic knockout, pharmacological blockade, and selective chemical knockout experiments confirmed that each receptor's activity contributed to the overall effect: glucagon increased energy expenditure, GLP-1 reduced caloric intake and improved glucose control, and GIP potentiated the incretin effect while buffering against glucagon's diabetogenic potential.
Finan, Brian; Yang, Bin; Ottaway, Nickki; Smiley, David L; Ma, Tao; Clemmensen, Christoffer; Chabenne, Joe; Zhang, Lianshan; Habegger, Kirk M; Fischer, Katrin; Campbell, Jonathan E; Sandoval, Darleen; Seeley, Randy J; Bleicher, Konrad; Uhles, Sabine; Riboulet, William; Funk, Jürgen; Hertel, Cornelia; Belli, Sara; Sebokova, Elena; Conde-Knape, Karin; Konkar, Anish; Drucker, Daniel J; Gelfanov, Vasily; Pfluger, Paul T; Müller, Timo D; Perez-Tilve, Diego; DiMarchi, Richard D; Tschöp, Matthias H ·
RPEP-02636 · 2015VIP is widely distributed in the central and peripheral nervous system and is also synthesized by immune cells, which express VIP receptors — creating an autocrine/paracrine immunoregulatory loop. VIP contributes to immune privilege in organs like the CNS (central nervous system) by maintaining immune deviation, and controls acute inflammation in peripheral immune organs.
The review summarizes VIP's broad immunomodulatory effects: it generally suppresses pro-inflammatory responses, shifts T cell differentiation toward regulatory phenotypes, and modulates cytokine production. Both endogenous VIP (naturally produced) and exogenous VIP (administered therapeutically) show potential in inflammatory and autoimmune disorders.
Ganea, D; Hooper, K M; Kong, W ·
RPEP-02638 · 2015A modified version of the melanotropin peptide Melanotan II (MTII) — called F Peptide — showed superpotent and ultra-prolonged pigmentation activity in frogs. The modification involved replacing arginine at position 8 with lysine and adding a glycine at position 10, expanding the cyclic ring. In vivo testing showed the F Peptide matched MTII's melanotropic potency but lasted significantly longer, making it one of the most sustained-action melanocortin agonists reported.
Gao, Liqian; Yu, Zhiqiang; Meng, Dan; Zheng, Fang; Ong, Yong S; Miao, Peng; Lee, Su S; Wen, Longping · Animal Study
RPEP-02640 · 2015Thymosin alpha-1 (Tα1) demonstrates significant potential as an immunotherapeutic agent in cancer treatment when combined with chemotherapy. Preclinical studies in murine models established the efficacy and safety of combining Tα1 with chemotherapy and cytokines, and these findings were confirmed in controlled clinical trials for metastatic melanoma and lung cancer. The peptide's dual action on both immune effector cells and tumor cells directly is considered critical for the success of chemo-immunotherapy protocols.
Garaci, Enrico; Pica, Francesca; Matteucci, Claudia; Gaziano, Roberta; D'Agostini, Cartesio; Miele, Martino Tony; Camerini, Roberto; Palamara, Anna Teresa; Favalli, Cartesio; Mastino, Antonio; Serafino, Annalucia; Sinibaldi Vallebona, Paola ·
RPEP-02642 · 2015The neuropeptide Substance P activates the cancer-driving receptors HER2 and EGFR in breast cancer cells through two pathways requiring c-Src kinase and metalloproteinases (MMPs). Inhibiting c-Src alone prevented Substance P-induced HER2 activation, while MMP inhibition reduced phosphorylation of both HER2 and EGFR. Dual inhibition of both c-Src and MMPs nearly abolished HER2 and EGFR activation and also reduced breast cancer cell viability and migration. These findings reveal that Substance P's tumor-promoting effects in breast cancer depend on both ligand-independent (c-Src) and ligand-dependent (MMP) signaling pathways.
Garcia-Recio, Susana; Pastor-Arroyo, Eva M; Marín-Aguilera, Mercedes; Almendro, Vanessa; Gascón, Pedro ·
RPEP-02646 · 2015Thymosin α1 enhanced HLA-I and HLA-II surface expression and secretion of IL-6, TNF-α, and IL-8 when dendritic cells were stimulated with viral TLR3 and TLR7/8 agonists. In H1N1 influenza A-infected DCs, Thymosin α1 increased maturation markers and type I and III interferon production.
In contrast, following bacterial TLR2 and TLR4 stimulation, as well as upon Bacillus Calmette-Guerin infection, Thymosin α1 drastically lowered DC maturation markers and cytokine production. This reveals a context-dependent dual effect: pro-inflammatory in viral settings and anti-inflammatory in bacterial settings.
Giacomini, Elena; Severa, Martina; Cruciani, Melania; Etna, Marilena Paola; Rizzo, Fabiana; Pardini, Manuela; Scagnolari, Carolina; Garaci, Enrico; Coccia, Eliana Marina ·
RPEP-02655 · 2015Across four AWARD randomized controlled trials with follow-up ranging from 26 to 104 weeks, dulaglutide demonstrated superior or noninferior glycemic control compared to all tested comparators:
• vs exenatide 10 µg twice daily: HbA1c reduction of -1.5% (1.5 mg) and -1.3% (0.75 mg) vs -0.99%
• vs sitagliptin 100 mg daily: -1.22% (1.5 mg) and -1.01% (0.75 mg) vs -0.6%
• vs insulin glargine: -1.08% (1.5 mg) vs -0.63% (significant); -0.76% (0.75 mg) vs -0.63% (not significant)
• vs liraglutide 1.8 mg daily: dulaglutide 1.5 mg was noninferior
More dulaglutide patients achieved HbA1c targets of <7% and ≤6.5%. Weight reduction was greater with dulaglutide than sitagliptin and exenatide. Hypoglycemia was infrequent across all dulaglutide groups.
Gurung, Tara; Shyangdan, Deepson S; O'Hare, Joseph Paul; Waugh, Norman ·
RPEP-02659 · 2015Amylin is a 37-amino acid peptide hormone co-secreted with insulin from pancreatic beta cells. Its receptors are unique multisubunit G protein-coupled receptors formed by combining a core receptor protein with receptor activity-modifying proteins (RAMPs), creating multiple receptor subtypes.
Key roles and findings from 25 years of research:
- Primary function: glucoregulation — amylin helps control blood sugar alongside insulin
- Appetite regulation: acts in circumventricular organs of the brain to reduce food intake
- Metabolic interactions: functionally interacts with cholecystokinin, leptin, and estradiol
- Additional effects: cardiovascular and bone actions have been reported
- Clinical use: pramlintide (amylin analog) is FDA-approved for type 1 and type 2 diabetes
- Obesity potential: clinical studies show amylin agonists promote weight loss, especially in combination therapy
Hay, Debbie L; Chen, Steve; Lutz, Thomas A; Parkes, David G; Roth, Jonathan D ·
RPEP-02660 · 2015This is the first complete two-dimensional map of iris nerve architecture. CGRP-positive nerve fibers constituted approximately 61% of anterior and 69% of posterior iris nerve content, while Substance P-positive fibers made up about 30.5% (anterior) and 20% (posterior). All SP-positive neurons in the trigeminal ganglia were also CGRP-positive, indicating co-expression. The iris has a complex nerve architecture with 4–5 stromal nerve rings, a superficial anterior network, and radial posterior nerve bundles running along the dilator muscle. The pupillary margin had the densest innervation. Non-neuronal SP-positive cells were also found in the anterior stroma.
He, Jiucheng; Bazan, Haydee E P ·
RPEP-02662 · 2015Using a combinatorial library approach with synthesis and deconvolution, researchers identified multiple geometrically diverse cyclic peptide scaffolds with good to excellent passive cell permeability. Experimental and computational analysis of structure-permeability relationships revealed specific structural and conformational factors governing passive membrane diffusion among cyclic peptide diastereomers.
Critically, single-point side-chain diversifications of one scaffold demonstrated that permeability could be maintained while varying the functional groups — meaning these scaffolds can be adapted for bioactivity screening against different targets without losing cell permeability. The results show that the chemical space of cell-permeable cyclic peptides extends far beyond known natural products.
Hewitt, William M; Leung, Siegfried S F; Pye, Cameron R; Ponkey, Alexandra R; Bednarek, Maria; Jacobson, Matthew P; Lokey, R Scott ·
RPEP-02663 · 2015Amylin plays three key roles in glucose homeostasis: suppressing post-meal glucagon release, delaying gastric emptying, and activating satiety centers in the brain to reduce caloric intake. Type 1 diabetes patients have absent amylin response to meals, while insulin-requiring type 2 patients have diminished response proportional to beta-cell impairment.
Pramlintide, the synthetic amylin analog, demonstrated significant HbA1c reductions in both type 1 and type 2 diabetes when added to insulin therapy, with favorable effects on body weight — an important advantage since insulin itself tends to promote weight gain. Key risks include increased hypoglycemia when combined with insulin and gastrointestinal side effects including nausea.
Hieronymus, Laura; Griffin, Stacy · Review
RPEP-02667 · 2015Topical BPC-157 accelerated wound closure in an alkali burn rat model compared to controls. By day 18 post-injury, treated wounds showed superior granulation tissue formation, reepithelialization, dermal remodeling, and collagen deposition on histological examination.
The mechanism was traced to angiogenesis (new blood vessel formation): BPC-157 increased VEGF expression in wounded skin, promoted proliferation and migration of human umbilical vein endothelial cells (HUVECs), and accelerated vascular tube formation in vitro. The ERK1/2 signaling pathway and its downstream targets (c-Fos, c-Jun, Egr-1) were identified as key mediators of these effects.
Huang, Tonglie; Zhang, Kuo; Sun, Lijuan; Xue, Xiaochang; Zhang, Cun; Shu, Zhen; Mu, Nan; Gu, Jintao; Zhang, Wangqian; Wang, Yukun; Zhang, Yingqi; Zhang, Wei ·
RPEP-02677 · 2015Substance P reduced ischemia-related lactate dehydrogenase release (a marker of cell damage) in both isolated heart preparations and hypoxic left ventricular tissue slices. It also reduced both apoptosis (programmed cell death) and necrosis (cell death from damage) in hypoxic tissue. Substance P induced AKT phosphorylation — a key step in cell survival signaling. Both the AKT inhibitor LY294002 and the NK-1 receptor antagonist L732138 blocked AKT phosphorylation and eliminated substance P's cardioprotective effect, confirming the NK-1 receptor/AKT mechanism.
Jubair, Shaiban; Li, Jianping; Dehlin, Heather M; Manteufel, Edward J; Goldspink, Paul H; Levick, Scott P; Janicki, Joseph S ·
RPEP-02680 · 2015Linking two different antimicrobial peptides together through a disulfide bond (heterodimerization) produced a compound that retained strong antibacterial activity while dramatically reducing toxicity to human cells. Specifically, the heterodimer of a lipopeptide (Laur-Orn-Orn-Cys-NH2) and an N-terminal fragment of human lactoferricin was nearly as active against bacteria as the more potent individual monomer, but was much less toxic (less hemolytic).
However, both homo- and heterodimerization reduced or eliminated antifungal activity, suggesting the structural changes that improve the safety profile against bacteria may compromise activity against fungi.
Kamysz, Elżbieta; Sikorska, Emilia; Dawgul, Małgorzata; Tyszkowski, Rafał; Kamysz, Wojciech · In Vitro
RPEP-02681 · 2015Three GHRH agonists — JI-38, MR-356, and MR-409 — reduced myocardial infarct size in rats after four weeks of treatment compared to placebo. The treated hearts showed increased numbers of cardiac c-kit+ progenitor cells (cardiac stem cells), more cellular mitotic divisions (active cell regeneration), and higher vascular density (new blood vessel formation).
One week after heart attack, MR-409 significantly reduced plasma levels of four inflammatory cytokines: IL-2, IL-6, IL-10, and TNF-α compared to placebo. Gene expression analysis revealed that MR-409 treatment inhibited pro-apoptotic molecules (cell death signals) and pro-fibrotic pathways (scarring) while elevating bone morphogenetic proteins involved in tissue repair. In cell culture, GHRH agonists decreased harmful calcium influx and improved cell survival under nutrient deprivation conditions.
Kanashiro-Takeuchi, Rosemeire M; Szalontay, Luca; Schally, Andrew V; Takeuchi, Lauro M; Popovics, Petra; Jaszberenyi, Miklos; Vidaurre, Irving; Zarandi, Marta; Cai, Ren-Zhi; Block, Norman L; Hare, Joshua M; Rick, Ferenc G ·
RPEP-02684 · 2015The NK1R antagonist (L-760735) suppressed Substance P-induced expression of IL-1β, IL-6, and IL-8 in human disc cells in a dose-dependent manner, confirming that NK1R is responsible for Substance P's pro-inflammatory effects in disc tissue.
Substance P stimulation increased phosphorylation of p38-MAPK and ERK1/2 but did not activate NF-κB p65 — a surprising finding since NF-κB is often the assumed inflammatory pathway. Specific inhibitors of p38 (SB203580) and ERK1/2 (PD98059) reduced SP-induced IL-6 production, confirming these pathways as the relevant signaling cascades. All three neurokinin receptors (NK1R, NK2R, NK3R) were detected in both annulus fibrosus and nucleus pulposus disc cells.
Kepler, Christopher K; Markova, Dessislava Z; Koerner, John D; Mendelis, Joseph; Chen, Chiu-Ming; Vaccaro, Alexander R; Risbud, Makarand V; Albert, Todd J; Anderson, D Greg ·
RPEP-02689 · 2015Plasma concentrations of BDNF, ADNP, and VIP in 31 treatment-naïve, newly diagnosed MS patients did not differ significantly from those in 36 healthy controls. Additionally, no correlations were found between these neurotrophic factors and inflammatory cytokines (IL-6, IL-10, TNF-α), C-reactive protein levels, or disability status as measured by the Expanded Disability Status Scale (EDSS).
This null result is informative — it suggests that in the earliest stages of MS, before treatment intervention, these neuroprotective peptides have not yet been detectably altered in peripheral blood.
Kochanowski, Jan; Uchman, Dorota; Litwiniuk, Anna; Kalisz, Malgorzata; Wolinska-Witort, Ewa; Martynska, Lidia; Baranowska, Boguslawa; Bik, Wojciech ·
RPEP-02690 · 2015This review maps the landscape of peptide drug delivery challenges and solutions. The central problem is that peptide drugs have poor bioavailability — they don't cross biological membranes well and break down quickly. While subcutaneous injection is the standard delivery method, most formulations don't provide sustained release, requiring frequent injections. The authors highlight porous silicon as a particularly promising carrier material that can hold exceptionally high peptide payloads and be tuned to release peptides slowly over time.
Kovalainen, Miia; Mönkäre, Juha; Riikonen, Joakim; Pesonen, Ullamari; Vlasova, Maria; Salonen, Jarno; Lehto, Vesa-Pekka; Järvinen, Kristiina; Herzig, Karl-Heinz ·
RPEP-02692 · 2015Researchers created a self-assembling peptide nanofiber hydrogel that can be injected by syringe and rapidly promotes blood vessel formation (angiogenesis) in living tissue. Within three weeks in rats, the hydrogel was infiltrated by blood-forming and tissue-building cells, formed a robust mature vascular network, showed no fibrous encapsulation (scar tissue walling off the implant), and was completely resorbed into the surrounding tissue.
The peptide design incorporated two key features: cell-mediated degradation sites (so the body's own cells break it down naturally) and proangiogenic sequences (that actively signal for new blood vessel growth). The injectable delivery eliminates the need for surgical implantation.
Kumar, Vivek A; Taylor, Nichole L; Shi, Siyu; Wang, Benjamin K; Jalan, Abhishek A; Kang, Marci K; Wickremasinghe, Navindee C; Hartgerink, Jeffrey D · In Vivo
RPEP-02693 · 2015A self-assembling multidomain peptide hydrogel delivered cytokines in a biphasic pattern that controlled immune cell behavior in both space and time. The nanofibrous scaffold recruited monocytes and macrophages, promoted their polarization toward a healing (M2) phenotype without creating inflammation, and was completely resorbed within 14 days of subcutaneous implantation. The injectable material recovered after shear stress, making it suitable for injection-based delivery.
Kumar, Vivek A; Taylor, Nichole L; Shi, Siyu; Wickremasinghe, Navindee C; D'Souza, Rena N; Hartgerink, Jeffrey D ·
RPEP-02700 · 2015Exogenous Substance P administration improved wound healing in diabetic mouse and rabbit models by inducing an acute inflammatory response and promoting macrophage polarization toward the M2 phenotype. Deficiency of Substance P or its receptor impaired wound healing, and diabetic skin showed reduced Substance P levels with increased degradation enzyme expression.
Critically, the study demonstrated a dual problem in diabetic skin: Substance P gene expression was decreased while neutral endopeptidase (the enzyme that degrades SP) was increased at both gene and protein levels. This creates a Substance P deficit that locks diabetic wounds into persistent, non-healing inflammation rather than the normal acute-to-proliferative healing sequence.
Leal, Ermelindo C; Carvalho, Eugénia; Tellechea, Ana; Kafanas, Antonios; Tecilazich, Francesco; Kearney, Cathal; Kuchibhotla, Sarada; Auster, Michael E; Kokkotou, Efi; Mooney, David J; LoGerfo, Frank W; Pradhan-Nabzdyk, Leena; Veves, Aristidis ·
RPEP-02704 · 2015The study mapped distinct neuropeptide-receptor systems for itch and pain in primate spinal cord:
**Itch-inducing systems:**
- β-endorphin (10-100 nmol) → mu-opioid receptor (MOP) → robust scratching
- Gastrin-releasing peptide (1-10 nmol) → BB2 receptor → equal scratching
- β-endorphin also attenuates inflammatory pain; GRP does not affect pain
**Pain-inhibiting only (no itch):**
- Enkephalins (100-1000 nmol) → pain inhibition
- Nociceptin-orphanin FQ (3-30 nmol) → pain inhibition
**Itch-inhibiting (no pain effect):**
- Dynorphin A(1-17) (10-100 nmol) → kappa-opioid receptor (KOP) → suppresses both β-endorphin- and GRP-induced itch
- Anti-itch effect reversed by KOP receptor antagonist nor-binaltorphimine
Lee, Heeseung; Ko, Mei-Chuan ·