RPEP-05589 · 2021Thymosin alpha-1 mitigated cytokine storm in COVID-19 patient blood cells by reducing excessive inflammatory cytokine production without broad immunosuppression.
Matteucci, Claudia; Minutolo, Antonella; Balestrieri, Emanuela; Petrone, Vita; Fanelli, Marialaura; Malagnino, Vincenzo; Ianetta, Marco; Giovinazzo, Alessandro; Barreca, Filippo; Di Cesare, Silvia; De Marco, Patrizia; Miele, Martino Tony; Toschi, Nicola; Mastino, Antonio; Sinibaldi Vallebona, Paola; Bernardini, Sergio; Rogliani, Paola; Sarmati, Loredana; Andreoni, Massimo; Grelli, Sandro; Garaci, Enrico · In Vitro
RPEP-05590 · 2021Real-world evidence for anti-CGRP monoclonal antibodies shows efficacy consistent with or exceeding clinical trial results, with maintained favorable safety profiles in routine clinical practice.
Mavridis, Theodoros; Deligianni, Christina I; Karagiorgis, Georgios; Daponte, Ariadne; Breza, Marianthi; Mitsikostas, Dimos D · Review
RPEP-05591 · 2021Randomized clinical trial showed no substantial modulation of empathy-related behavioral or neural responses by intranasal oxytocin administration compared to placebo.
Mayer, Annalina V; Wermter, Anne-Kathrin; Stroth, Sanna; Alter, Peter; Haberhausen, Michael; Stehr, Thomas; Paulus, Frieder M; Krach, Sören; Kamp-Becker, Inge · Clinical Trial
RPEP-05592 · 2021Injectable magnetic-responsive short-peptide supramolecular hydrogels demonstrated magnetically guided assembly ex vivo, providing spatially controllable scaffolds with potential for tissue engineering applications.
Mañas-Torres, Mari C; Gila-Vilchez, Cristina; Vazquez-Perez, Francisco J; Kuzhir, Pavel; Momier, David; Scimeca, Jean-Claude; Borderie, Arnaud; Goracci, Marianne; Burel-Vandenbos, Fanny; Blanco-Elices, Cristina; Rodriguez, Ismael A; Alaminos, Miguel; de Cienfuegos, Luis Álvarez; Lopez-Lopez, Modesto T · Animal Study
RPEP-05593 · 2021Cysteinyl radicals enable novel peptide synthesis strategies including stapling and selective modifications, while also playing important roles in natural enzyme catalysis and redox biology.
McLean, Joshua T; Benny, Alby; Nolan, Mark D; Swinand, Glenna; Scanlan, Eoin M · Review
RPEP-05595 · 2021Knocking down the T2R14 bitter taste receptor in gingival epithelial cells significantly decreased the internalization of S. aureus, while S. mutans internalization was unaffected. The two bacteria also triggered distinct T2R14-dependent immune responses: S. aureus infection induced secretion of the antimicrobial peptide human β-defensin-2 (hBD-2), whereas S. mutans infection induced IL-8 secretion instead.
Additionally, when gum cells were primed with S. mutans competence stimulating peptide CSP-1, they inhibited the growth of S. aureus but not S. mutans — suggesting cross-species bacterial defense mediated through T2R14 signaling. The receptor's role in cytoskeletal reorganization appears to be the mechanism behind these differential internalization effects.
Medapati, Manoj Reddy; Bhagirath, Anjali Yadav; Singh, Nisha; Schroth, Robert J; Bhullar, Rajinder P; Duan, Kangmin; Chelikani, Prashen · In Vitro
RPEP-05598 · 2021The authors hypothesize that age-dependent differences in Substance P (SP) levels explain why children rarely develop severe COVID-19 while elderly patients suffer the worst outcomes. Substance P is a neuropeptide produced in the brainstem's spinal trigeminal nucleus that drives inflammation in the airways. The authors propose that higher SP activity in elderly patients amplifies the inflammatory cascade in COVID-19, worsening respiratory illness.
Their central recommendation: NK-1R antagonists — drugs that block the Substance P receptor — should be urgently investigated as COVID-19 treatments. These drugs are already FDA-approved for other uses (notably as anti-nausea medications), making rapid repurposing feasible.
Mehboob, Riffat; Lavezzi, Anna Maria · Review
RPEP-05600 · 2021Engineered probiotic bacteria can be genetically modified to produce antimicrobial peptides (AMPs) directly inside the gut, providing a living drug delivery system that continuously manufactures antibiotics right where they're needed. This review covers the current state of AMP-producing probiotics, discussing how oral delivery via probiotic bacteria protects AMPs from degradation in the digestive tract — solving one of the biggest challenges in peptide drug delivery.
Key applications include treating drug-resistant enteric pathogens (gut infections caused by antibiotic-resistant bacteria) and actively remodeling the gut microbiome in real time. The review also addresses strategies to enhance probiotic colonization of the gut for sustained AMP delivery.
Mejía-Pitta, Adriana; Broset, Esther; de la Fuente-Nunez, Cesar · Review
RPEP-05605 · 2021Twenty-eight melanoma patients were randomized to four adjuvant groups for transdermal peptide vaccination (12 melanoma peptides + tetanus helper peptide + GM-CSF). CD8+ T cell responses to transdermal vaccination in DMSO occurred in 83% (group 3) and 86% (group 4) of participants, dramatically exceeding responses with IFA: 29% (group 1) and 14% (group 2). CD4+ T cell responses to tetanus peptide occurred in 61% overall, with large durable responses in DMSO groups. However, 5/7 patients receiving DMSO + imiquimod developed severe rash, one dose-limiting. Ten-year overall survival was 67% and disease-free survival was 44%.
Meneveau, Max O; Petroni, Gina R; Salerno, Elise P; Lynch, Kevin T; Smolkin, Mark; Woodson, Elizabeth; Chianese-Bullock, Kimberly A; Olson, Walter C; Deacon, Donna; Patterson, James W; Grosh, William W; Slingluff, Craig L · Clinical Trial
RPEP-05606 · 2021Using liquid chromatography coupled with high-resolution Orbitrap mass spectrometry (LC-HRMS), researchers successfully identified melanotan II and bremelanotide in 8 confiscated samples without requiring reference standards.
Identification was achieved through three complementary approaches: accurate mass measurement of protonated molecular ions (MH+), analysis of isotopic patterns and relative isotopic abundance (RIA) values, and accurate mass measurement of collision-induced fragment ions.
The samples had been confiscated by police alongside anabolic steroids, hormone modulators, sexual enhancers, and stimulants — illustrating that these peptides circulate within the broader black market for performance and image-enhancing drugs (PIEDs).
Mestria, Serena; Odoardi, Sara; Frison, Giampietro; Strano Rossi, Sabina · In Vitro
RPEP-05609 · 2021From a screen of 75 peptide FRET pairs, asparagine-containing peptides emerged as being cleaved far more rapidly than traditional valine-citrulline linkers by lysosomal extracts while maintaining excellent plasma stability. These linkers were cleaved by legumain (an asparaginyl endopeptidase overexpressed in many cancers). MMAE-containing ADCs with the new linkers showed cytotoxicity comparable to standard ValCit ADCs. Critically, the Asn-containing linkers were completely stable to human neutrophil elastase (thought to cause ADC-related neutropenia and thrombocytopenia). Serum stability was excellent: >85% drug retention after 1 week in mouse and human serum, and <10% cleavage of FRET pairs after 18 hours.
Miller, Jared T; Vitro, Caitlin N; Fang, Siteng; Benjamin, Samantha R; Tumey, L Nathan · In Vitro
RPEP-05610 · 2021A transdermal microneedle patch delivering abaloparatide (an osteoporosis peptide drug) was successfully self-administered by all 22 postmenopausal women enrolled in the trial, with a 99.7% success rate on first application. The patch delivered consistent drug levels over 29 days, with bone formation marker s-PINP increasing by 45.4% at Day 15 and 64.4% at Day 29 — similar to results seen with the standard subcutaneous injection.
The patch was applied to the thigh for 5 minutes daily at a 300 μg dose. Drug absorption was rapid (peak levels reached in about 20 minutes). Side effects were mostly mild application-site reactions (redness, pain, swelling), and no one dropped out due to adverse events. Patient acceptability scored approximately 4.5 out of 5.
Miller, Paul D; Troy, Steven; Weiss, Richard J; Annett, Miriam; Schense, Jason; Williams, Setareh A; Mitlak, Bruce · Clinical Trial
RPEP-05612 · 2021Tirzepatide is a synthetic 39-amino-acid peptide that activates both GIP and GLP-1 receptors simultaneously — a first-in-class 'twincretin.' Early clinical trials (phase 1 and 2) demonstrated potent glucose-lowering and weight loss effects with a side effect profile comparable to existing GLP-1 receptor agonists.
The dual-agonist concept was built on research showing that co-infusion of GIP and GLP-1 together produces synergistic effects — significantly greater insulin response and glucagon suppression than either hormone alone. Tirzepatide is built on the native GIP sequence with modifications that also activate the GLP-1 receptor, representing a new pharmacological approach to type 2 diabetes.
Min, Thinzar; Bain, Stephen C · Review
RPEP-05620 · 2021LAG3-Ig-P5-immunoliposomes outperformed soluble LAG3-Ig + P5 across all measured outcomes:
- Dendritic cell maturation: markedly induced by liposome-conjugated LAG3-Ig through multivalent MHC class II binding, more efficiently than free LAG3-Ig
- T cell responses: higher percentages of both CD4+ and CD8+ T cells in the spleen
- Tumor infiltration: more rapid and pronounced infiltration of effector T cells into tumor tissue
- Anti-tumor efficacy: greater tumor regression and prolonged survival in treated mice
The PEGylated liposome format enhanced LAG3-Ig's adjuvant activity by presenting it in a multivalent configuration that amplified its interaction with immune cells.
Mohammadian Haftcheshmeh, Saeed; Zamani, Parvin; Mashreghi, Mohammad; Nikpoor, Amin Reza; Tavakkol-Afshari, Jalil; Jaafari, Mahmoud Reza · Animal Study
RPEP-05625 · 2021αCT1-treated scars showed significantly less collagen fiber alignment compared to vehicle-control treated wounds within the same patient at 29 days post-wounding — a pattern resembling unwounded skin rather than typical scar tissue.
The mechanism was traced to αCT1 causing decreased directionality of fibroblast movement during wound closure, which was demonstrated in both mouse and human fibroblast scratch wound assays. An agent-based computational model parameterized with the motility data successfully predicted the collagen alignment patterns observed in human and animal experiments. Phase II clinical trials had previously reported 47% improvement in scar appearance at 9 months post-surgery.
Montgomery, Jade; Richardson, William J; Marsh, Spencer; Rhett, J Matthew; Bustos, Francis; Degen, Katherine; Ghatnekar, Gautam S; Grek, Christina L; Jourdan, L Jane; Holmes, Jeffrey W; Gourdie, Robert G · Clinical Trial
RPEP-05626 · 2021PACAP plays an important role in the pathogenesis of headaches (particularly migraine), post-traumatic stress disorder, and drug/alcohol/smoking addiction. VIP has demonstrated therapeutic effects in autoimmune and inflammatory disorders, especially rheumatoid arthritis. The development of specific drugs targeting this system — including monoclonal antibodies against VIP and PACAP — has advanced to therapeutic trials in some cases.
Moody, Terry W; Jensen, Robert T · Review
RPEP-05629 · 2021After four rounds of intranodal vaccination with neoantigen peptide-loaded dendritic cells, the patient experienced: remarkable decline in CA-125 levels (ovarian cancer marker), decreased tumor cells in malignant ascites, and improvement in tumor-related symptoms including respiratory discomfort — all without adverse reactions.
Immunologically, the vaccine generated a detectable T cell response against an HLA-A2402-restricted neoantigen peptide derived from mutated PPM1F protein, confirmed by IFN-γ ELISPOT assay. Critically, neoantigen-specific T cell receptors (TCRs) were detected in tumor-infiltrating lymphocytes post-vaccination, demonstrating the vaccine successfully directed immune cells into the tumor.
Morisaki, Takashi; Hikichi, Tetsuro; Onishi, Hideya; Morisaki, Takafumi; Kubo, Makoto; Hirano, Tatsuya; Yoshimura, Sachiko; Kiyotani, Kazuma; Nakamura, Yusuke · Clinical Trial
RPEP-05633 · 2021Over 80 peptide drugs have reached the market since insulin's introduction, covering a remarkably diverse range of therapeutic areas. The review identifies several key waves of peptide drug development:
1) Early hormone-based drugs: insulin, oxytocin, vasopressin, ACTH
2) Medicinal chemistry era: rational design and chemical modifications to improve stability and selectivity
3) Nature-derived peptides: venom-derived drugs (ziconotide from cone snails, exenatide from Gila monster), natural product-inspired designs
4) Molecular biology advances: recombinant production, phage display, mRNA display
5) Emerging strategies: integrated venomics (systematic venom mining), peptide-display libraries, AI-guided design
The authors emphasize that lessons from earlier approaches remain highly relevant, and that peptide drugs occupy a unique pharmaceutical 'sweet spot' between small molecules and biologics.
Muttenthaler, Markus; King, Glenn F; Adams, David J; Alewood, Paul F ·
RPEP-05635 · 2021Hippocampal Y2R blockade improved spatial memory, and learning dynamically changed Y2R/Y1R expression in hippocampus and prefrontal cortex.
Méndez-Couz, Marta; Manahan-Vaughan, Denise; Silva, Ana Paula; González-Pardo, Héctor; Arias, Jorge Luis; Conejo, Nélida María · Animal Study
RPEP-05640 · 2021Three novel WT1 Th peptides strongly enhanced CTL induction, maintenance, and tumor rejection when co-immunized with WT1 CTL peptide in mice.
Nakajima, Hiroko; Nakata, Jun; Imafuku, Kanako; Hayashibara, Hiromu; Isokawa, Kazuki; Udaka, Keiko; Fujiki, Fumihiro; Morimoto, Soyoko; Hasegawa, Kana; Hosen, Naoki; Hashii, Yoshiko; Nishida, Sumiyuki; Tsuboi, Akihiro; Oka, Yoshihiro; Oji, Yusuke; Sogo, Shinji; Sugiyama, Haruo · Animal Study
RPEP-05641 · 2021This comprehensive review covers the entire GLP-1 receptor agonist class for type 2 diabetes, documenting their evolution from twice-daily exenatide (2005) to once-weekly and oral formulations. Key conclusions: GLP-1 RAs reduce HbA1c and body weight without intrinsic hypoglycemia risk, are now recommended as the preferred first injectable therapy before insulin, and several cardiovascular outcome trials have shown they prevent heart attacks, strokes, and associated mortality in patients with atherosclerotic disease. Semaglutide emerged as the most effective for both glucose lowering and weight loss. Novel indications being explored include type 1 diabetes, neurodegenerative diseases, and psoriasis.
Nauck, Michael A; Quast, Daniel R; Wefers, Jakob; Meier, Juris J · Review
RPEP-05643 · 2021The team used mass spectrometry to compare protein fragments displayed on CLL cells versus normal tissue. They found several tumor-associated fragments that appeared often across many CLL patients.
These fragments triggered immune responses from both existing and newly created T cells in CLL patients and healthy volunteers. The researchers packaged these peptides into a pre-made warehouse, so doctors could quickly assemble a personalized multi-peptide vaccine for each patient without starting from scratch.
This matters because CLL has very few mutations, making it hard to find unique cancer targets. The warehouse approach sidesteps this problem by using non-mutated but tumor-associated peptides that still provoke an immune response.
Nelde, Annika; Maringer, Yacine; Bilich, Tatjana; Salih, Helmut R; Roerden, Malte; Heitmann, Jonas S; Marcu, Ana; Bauer, Jens; Neidert, Marian C; Denzlinger, Claudio; Illerhaus, Gerald; Aulitzky, Walter Erich; Rammensee, Hans-Georg; Walz, Juliane S · Translational
RPEP-05644 · 2021In a 72-week trial published in the New England Journal of Medicine, semaglutide at 0.4 mg daily achieved NASH resolution (without worsening fibrosis) in 59% of patients, compared to 17% on placebo (P<0.001). This was confirmed by liver biopsy — the gold standard for assessing liver disease.
However, semaglutide did not significantly improve fibrosis: 43% of the 0.4 mg group had fibrosis improvement versus 33% on placebo (P=0.48, not significant). Patients on the highest dose lost an average of 13% of their body weight compared to 1% on placebo. GI side effects were common — 42% experienced nausea and 15% had vomiting at the 0.4 mg dose. A small neoplasm signal was noted (3 malignancies in semaglutide groups vs. 0 on placebo), though no pattern was evident.
Newsome, Philip N; Buchholtz, Kristine; Cusi, Kenneth; Linder, Martin; Okanoue, Takeshi; Ratziu, Vlad; Sanyal, Arun J; Sejling, Anne-Sophie; Harrison, Stephen A · Randomized Controlled Trial (Phase 2)
RPEP-05645 · 2021A line-targeting peptide serum (LTPS) containing neuromodulating peptides significantly improved expression lines compared to placebo at all measured time points — as early as 15 minutes after first application and sustained through 12 weeks of twice-daily use.
Board-certified dermatologist evaluation confirmed the peptide serum outperformed placebo for both expression lines and overall skin health parameters at Weeks 4, 8, and 12. These clinical assessments were supported by objective imaging: VISIA photography and 3D PRIMOS CR wrinkle analysis both substantiated the serum's efficacy. The treatment was well tolerated with no reported safety concerns.
Nguyen, Thu Q; Zahr, Alisar S; Kononov, Tatiana; Ablon, Glynis · Randomized Controlled Trial
RPEP-05653 · 2021After 7 weeks of very-low-energy dieting producing 12 kg weight loss (P < 0.001), participants were randomized to higher-satiety food (HSF, more protein/fiber, less fat) or lower-satiety food (LSF) diets for 24-week weight maintenance. Key findings:
- Diet composition made no difference: HSF and LSF groups showed identical changes in fasting ghrelin, leptin, insulin, and glucose
- Weight regain was modest: only 1.3 kg (P = 0.004) over 24 weeks
- Hormonal adaptations persisted: ghrelin increased, leptin/insulin/glucose decreased vs. pre-diet (all P < 0.001)
- Peptide YY (PYY) did not differ from pre-diet levels
- Body composition tracking: ghrelin inversely correlated with fat-free mass changes (P = 0.002); leptin and insulin positively correlated with fat mass changes (P < 0.05)
Näätänen, Mari; Kolehmainen, Marjukka; Laaksonen, David E; Herzig, Karl-Heinz; Poutanen, Kaisa; Karhunen, Leila · Clinical Trial
RPEP-05654 · 2021Linear beta-defensins from snakes were most active against E. coli, M. luteus, C. freundii, and S. aureus. Shorter derived peptides (7-14 amino acids) also showed antibacterial activity against those bacteria plus K. pneumoniae.
However, none of the derived peptides killed any of the four fungi tested (C. albicans, C. neoformans, T. rubrum, A. fumigatus). The key difference was the cysteine-to-serine substitution used to create the linear peptides. This suggests that the disulfide bridges formed by cysteines are essential for antifungal activity but less important for killing bacteria.
Adding tryptophan (an amino acid) to the derived peptides improved their antibacterial potency. The researchers concluded that while snake beta-defensins are not the most powerful antimicrobials, they serve as useful starting templates for designing new antibiotics.
Oguiura, Nancy; Corrêa, Poliana Garcia; Rosmino, Isabella Lemos; de Souza, Ana Olívia; Pasqualoto, Kerly Fernanda Mesquita · Basic Research
RPEP-05662 · 2021Oral delivery of peptide drugs faces three main barriers: enzymatic degradation (stomach acid and enzymes break them apart), poor membrane permeability (they are too large and charged to cross the gut lining), and instability (they unfold and lose function).
Computer-aided drug design (CADD) addresses these by modeling molecular interactions at the atomic level. Researchers can simulate how a peptide interacts with its receptor, screen formulation ingredients for compatibility, and predict which chemical modifications might improve stability or absorption.
The review highlights that CADD can pre-screen excipients (inactive ingredients in the formulation) and predict absorption before expensive lab experiments. This speeds up development and reduces costs for oral peptide formulations.
Pandya, Anjali K; Patravale, Vandana B · Review
RPEP-05664 · 2021LL-37 levels in nasal secretions were inversely associated with multiple measures of bronchiolitis severity. Higher LL-37 meant:
- Shorter hospitalization (rho = -0.340, p = 0.001)
- Less medication use (p = 0.001)
- Shorter oxygen supplementation (rho = -0.339, p = 0.001)
- Shorter IV fluid administration (rho = -0.323, p = 0.001)
These associations remained significant after adjusting for confounding factors like age and other variables.
Notably, serum vitamin D levels were not associated with nasal LL-37 levels, challenging the assumption that vitamin D drives LL-37 production in the airways. Beta-defensin-2 nasal levels also showed no connection to disease severity.
Papadaki, Maria; Marmarinos, Antonios; Tsolia, Maria; Gourgiotis, Dimitrios; Soldatou, Alexandra · Observational
RPEP-05665 · 2021One of the biggest barriers in gene therapy is the endosomal trap. Cells engulf nanoparticles carrying therapeutic genes, but the particles get stuck inside endosomes and are destroyed before they can deliver their cargo to the cell nucleus.
Melittin, a 26-amino-acid peptide from bee venom, can disrupt endosomal membranes and release the trapped cargo. However, melittin is extremely toxic to mammalian cells at normal concentrations because it also destroys the outer cell membrane.
Researchers have addressed this by modifying melittin's amino acid sequence to reduce its toxicity while preserving its membrane-disrupting ability. Strategies include making pH-sensitive versions that only activate inside acidic endosomes (where the gene cargo is trapped) and conjugating melittin to nanoparticle carriers so it acts locally rather than freely.
Paray, Bilal Ahamad; Ahmad, Aqeel; Khan, Javed Masood; Taufiq, Faisal; Pathan, Aslam; Malik, Ajamaluddin; Ahmed, Mohammad Z · Review
RPEP-05667 · 2021M. restricta and M. globosa activated the NLRP3-ASC inflammasome in human keratinocytes, triggering IL-1β secretion — a key inflammatory signal. All three Malassezia species variably induced the antimicrobial peptides thymic stromal lymphopoietin, β-defensin 2, and LL-37.
Each species created a distinct inflammatory profile: M. sympodialis significantly increased IL-8 and IL-22 protein levels, while M. globosa increased CCL17 mRNA and M. restricta increased CCL22 mRNA. This species-specific pattern of inflammasome activation, cytokine release, and antimicrobial peptide induction suggests that different Malassezia species may drive the distinct clinical presentations of conditions like dandruff versus atopic dermatitis.
Park, Hye Ree; Oh, Jee Hye; Lee, Yu Jin; Park, Song Hee; Lee, Yang Won; Lee, Seongju; Kang, Hoon; Kim, Jung Eun · Basic Research
RPEP-05673 · 2021Neuropeptides play a significant and underappreciated role in asthma beyond traditional inflammatory mechanisms. The airway epithelium contains pulmonary neuroendocrine cells that release neuropeptides including substance P (SP), neurokinin A (NKA), vasoactive intestinal peptide (VIP), CGRP, neuropeptide Y (NPY), and orphanin FQ (N/OFQ) after allergen exposure.
These neuropeptides have opposing effects: SP, NKA, and serotonin drive inflammation (promoting chemokine synthesis in eosinophils, mast cells, and neutrophils), while VIP and N/OFQ provide anti-inflammatory and bronchodilatory effects. CGRP and acetylcholine have dual roles depending on which receptor pathway is activated — for example, ACh acting on M3 receptors causes bronchoconstriction and mucus overproduction, while ACh acting on α7nAChR receptors on ILC2 cells actually reduces inflammation.
Experimental NK1R/NK2R antagonists and exogenous VIP administration have decreased inflammatory mediators in studies, suggesting that targeting neuropeptide pathways could be a novel therapeutic approach for asthma.
Pavón-Romero, Gandhi F; Serrano-Pérez, Nancy Haydée; García-Sánchez, Lizbeth; Ramírez-Jiménez, Fernando; Terán, Luis M · Review
RPEP-05675 · 2021Three peptide variants were tested:
1. bLfcin (natural, can flex between structures)
2. bLfcin DB (locked with a disulfide bond)
3. bLfcin C36G (mutation prevents disulfide formation)
In water, bLfcin and C36G had similar secondary structures. Under less hydrophobic conditions, bLfcin and DB had similar structures. This confirms bLfcin can switch between conformations depending on the environment.
All three killed E. coli ATCC 25922, Salmonella typhimurium, and Shigella flexneri. None were effective against S. aureus. The natural bLfcin showed higher antibacterial activity than both variants, suggesting its ability to change shape gives it an advantage when encountering different bacterial membranes.
Pei, Jie; Xiong, Lin; Bao, Pengjia; Chu, Min; Yan, Ping; Guo, Xian · Basic Research
RPEP-05682 · 2021Rimegepant is a small molecule that blocks the CGRP receptor. It was developed based on the improved understanding of migraine as a neurovascular condition involving vasoactive peptides, particularly CGRP.
It is approved for acute treatment of migraine in adults with or without aura. In clinical trials, it decreased pain and reduced symptoms associated with migraine attacks.
Rimegepant is part of a wave of new migraine treatments in the past 3 years that includes:
- Acute treatments: lasmiditan, rimegepant, ubrogepant
- Preventive treatments: erenumab, fremanezumab, galcanezumab, eptinezumab
All of these target the neurovascular migraine pathway, with CGRP being the central peptide involved.
Peters, Golden L; Hennessey, Erin K · Review
RPEP-05686 · 2021The [Ser3,7,12,16]-RTD-2 analog, where four cysteines were replaced with serines to simplify the structure, selectively targeted various breast cancer cell types.
Immunoprecipitation studies identified eleven proteins that the peptide interacted with in both MDA-MB-231 (triple-negative) and T47D (hormone receptor-positive) breast cancer cell lines. These proteins were primarily nuclear and strongly connected to the proteasomal protein degradation pathway.
The ubiquitin-proteasome system is markedly increased in breast cancer patients. Proteasome inhibitors (like bortezomib) are already used in blood cancers. This study suggests that defensin-based peptides could offer a new way to modulate this system in breast cancer specifically.
Pianka, Joanna; Gruba, Natalia; Kitowska, Kamila; Mieczkowski, Kamil; Wysocka, Magdalena; Sądej, Rafał; Lesner, Adam · Basic Research
RPEP-05689 · 2021Capromorelin activates the ghrelin receptor (GHSR), which is found on pancreatic delta cells that produce somatostatin. Activating delta cells was expected to suppress insulin secretion.
On day 1:
- Fasting blood glucose increased by 13 mg/dL (p < 0.0001)
- Insulin decreased (p = 0.03)
- Glucagon was unchanged
- First-phase insulin response (FPIR) during glucose tolerance test dropped by 72% (from 17,437 to 4,931 ng/L/15min, p = 0.004)
Days 2-4:
- Mean interstitial glucose rose by 19 mg/dL (p = 0.03)
- Glycemic variability increased (SD 9.7 vs 5.0, p = 0.02)
By day 30:
- Glucose tolerance returned to baseline
- Glycemic variability normalized
- But FPIR was still partially blunted (9,993 vs 17,437, p = 0.045)
The body appeared to compensate for the initial insulin suppression over time.
Pires, J; Greathouse, R L; Quach, N; Huising, M O; Crakes, K R; Miller, M; Gilor, C · Animal Study
RPEP-05690 · 2021Three gut peptide hormones — CCK, GLP-1, and PYY — serve as the primary signaling molecules in the satiety system, released by enteroendocrine cells (EECs) in response to specific macronutrients detected through nutrient-sensing receptors. The gut microbiota directly interacts with EECs and modulates hormone release by changing the gut environment and producing metabolites. Diet shapes the microbiome, which shapes hormone release, which shapes brain appetite signals — creating the microbiota-gut-brain axis (MGBA). The review proposes that bioactive compounds exploiting these nutrient-sensing mechanisms could become functional foods or drugs for obesity.
Pizarroso, Nuria A; Fuciños, Pablo; Gonçalves, Catarina; Pastrana, Lorenzo; Amado, Isabel R · Review
RPEP-05691 · 2021The biotechnological protocol combined membrane ultrafiltration (to concentrate proteins from waste whey) with fermentation by a selected L. helveticus strain. The fermented product had high anti-ACE activity.
Peptides responsible for the activity were identified by mass spectrometry. Their sequences overlapped with known kappa-casein antihypertensive fragments.
Fortified ricotta cheese results:
- 5% fortification: a 100g portion contained approximately 30 mg of bioactive peptides
- Significantly higher anti-ACE activity compared to control and unfermented versions
- Moderate changes in texture (increased hardness and chewiness)
- Decreased milk odor/taste but improved flavor persistence and sapidity
- Microbiological quality was acceptable
Pontonio, Erica; Montemurro, Marco; De Gennaro, Gina Valeria; Miceli, Valerio; Rizzello, Carlo Giuseppe · Basic Research
RPEP-05696 · 2021The study profiled the HLA class I immunopeptidome (all peptides displayed on cell surface immune markers) in melanoma (high tumor mutation burden) and EGFR-mutant lung adenocarcinoma (low mutation burden).
Similar numbers of peptides were identified from both cancer types, despite their different mutation rates. Key findings:
- 12 variant peptides from tumor-specific mutations
- 40 cancer germline (CG) antigen-derived peptides from a custom database of 285 CG antigens
- Over 1,000 post-translationally modified (PTM) peptides representing 58 different PTMs
- 44 novel peptides encoded by long noncoding RNA (lncRNA), a previously unrecognized source of cancer antigens
All key findings were validated using synthetic peptide matching and HLA binding assays. The lncRNA-derived peptides represent a completely new class of potential immunotherapy targets.
Qi, Yue A; Maity, Tapan K; Cultraro, Constance M; Misra, Vikram; Zhang, Xu; Ade, Catherine; Gao, Shaojian; Milewski, David; Nguyen, Khoa D; Ebrahimabadi, Mohammad H; Hanada, Ken-Ichi; Khan, Javed; Sahinalp, Cenk; Yang, James C; Guha, Udayan · Basic Research
RPEP-05700 · 2021MRGPRX2 on mast cells recognizes an unusually diverse set of ligands:
Natural ligands: host defense peptides, substance P, VIP, eosinophil granule proteins
Drug ligands: compound 48/80, mastoparan (bee venom), quinolone antibiotics, neuromuscular blockers, morphine, vancomycin
In host defense, the mouse homolog Mrgprb2 helps mast cells detect bacterial peptides and release antimicrobial peptides and immune mediators.
In disease:
- MRGPRX2 is linked to non-IgE drug hypersensitivity reactions (explaining why some people react to certain drugs without allergies)
- Implicated in asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria
- May play a role in chronic inflammation through persistent mast cell activation
- Also involved in tissue homeostasis and repair
Quan, Paola Leonor; Sabaté-Brescó, Marina; Guo, Yanru; Martín, Margarita; Gastaminza, Gabriel · Review
RPEP-05701 · 2021Both GLP-1 receptor agonists produced comparable effects on:
- Macronutrient and energy intake (equally reduced)
- Body weight loss
- Appetite reduction
The key mechanistic finding was that weight loss and appetite reduction were NOT related to delayed gastric emptying or GI side effects (p > 0.05 for both). This challenges the common assumption that GLP-1 drugs reduce appetite mainly by slowing stomach emptying or causing nausea.
Both drugs improved exocrine pancreas function (faecal elastase and serum beta-carotin increased), suggesting GLP-1 drugs may benefit pancreatic enzyme output.
Liraglutide specifically increased serum lipase by 18.3 U/L (p = 0.0001), while lixisenatide did not. This lipase elevation is clinically relevant because lipase rises can indicate pancreatic stress, though in this case it was associated with improved pancreatic markers overall.
Quast, Daniel R; Nauck, Michael A; Schenker, Nina; Menge, Björn A; Kapitza, Christoph; Meier, Juris J · Randomized Controlled Trial
RPEP-05710 · 2021BPC 157 therapy initiated 2 weeks after fistula creation (when healing had failed) reversed the course within 1 week across all regimens (10 µg/kg and 10 ng/kg, IP or oral). All treated rats showed: cessation of urinary leakage through vagina, increased epithelization, collagenization, granulation tissue and neovascularization, decreased inflammation and necrosis. By study end (day 56), treated rats exhibited 5x larger bladder volume capacity before leaking compared to healthy controls, complete vesical and vaginal defect closure, and zero stone formation — versus persistent fistulas and stone formation in untreated controls.
Rasic, Domagoj; Zenko Sever, Anita; Rasic, Fran; Strbe, Sanja; Rasic, Zarko; Djuzel, Antonija; Duplancic, Bozidar; Boban Blagaic, Alenka; Skrtic, Anita; Seiwerth, Sven; Sikiric, Predrag; Sever, Marko · Animal Study
RPEP-05714 · 2021GHRH antagonist MIA-602 produced anxiolytic and antidepressant effects in mice after 4 weeks of subcutaneous treatment, mediated through Nrf2 and BDNF signaling in the hippocampus and prefrontal cortex.
Recinella, Lucia; Chiavaroli, Annalisa; Orlando, Giustino; Ferrante, Claudio; Veschi, Serena; Cama, Alessandro; Marconi, Guya Diletta; Diomede, Francesca; Gesmundo, Iacopo; Granata, Riccarda; Cai, Renzhi; Sha, Wei; Schally, Andrew V; Brunetti, Luigi; Leone, Sheila · Animal Study
RPEP-05716 · 2021Both GHRH analogs — the antagonist MIA-690 and the agonist MR-409 — attenuated DSS-induced colitis in mice, improving clinical symptoms and reducing histopathological damage.
In ex vivo colon tissue, both peptides inhibited production of pro-inflammatory and oxidative markers triggered by bacterial toxin (LPS). In live mice, both reduced pain responses in hot plate and formalin tests and decreased sensitivity to inflammatory stimuli.
MIA-690 showed superior efficacy compared to MR-409, more strongly inhibiting prostaglandin E2, 8-iso-PGF2α, serotonin, TNF-α, IL-6, and nitric oxide synthase gene expression in colitis-affected colon tissue. MIA-690 also uniquely decreased serum IGF-1 levels in colitis mice, which may explain its stronger anti-inflammatory and antioxidant activity.
Recinella, Lucia; Chiavaroli, Annalisa; Di Valerio, Valentina; Veschi, Serena; Orlando, Giustino; Ferrante, Claudio; Gesmundo, Iacopo; Granata, Riccarda; Cai, Renzhi; Sha, Wei; Schally, Andrew V; Lattanzio, Rossano; Brunetti, Luigi; Leone, Sheila · Animal Study
RPEP-05717 · 2021New-generation CPPs address three major limitations of earlier peptides:
1. **Cell selectivity**: Hybrid designs combine homing sequences for tissue targeting with activation sequences that only work at the target site, dramatically improving specificity.
2. **Protease stability**: Conjugation to nanoparticles and structural modifications protect CPPs from enzymatic degradation in the body.
3. **Endosomal escape**: Engineered sequences enable CPPs to break out of endosomes (cellular compartments that trap delivered cargo), ensuring drugs actually reach their intracellular targets.
Several naturally tumor-selective CPPs were highlighted — azurin, crotamine, maurocalcine, lycosin-I, buffalo cathelicidin, and peptide CB5005 — which can both penetrate cancer cell membranes and directly exert cytotoxic effects through intracellular signaling pathways.
Notably, certain CPPs can now penetrate the blood-brain barrier, skin, and eye tissues, enabling non-invasive delivery via sprays, creams, and drops instead of injections.
Reissmann, Siegmund; Filatova, Margarita P · Review
RPEP-05720 · 2021MOTS-c, a peptide encoded by mitochondrial DNA, significantly enhanced physical performance in young (2 months), middle-aged (12 months), and old (22 months) mice. Most remarkably, when MOTS-c treatment was started very late in life (23.5 months — equivalent to roughly 70+ human years) at just 3 times per week, it still increased physical capacity and healthspan.
The study also showed that exercise naturally increases MOTS-c levels in both skeletal muscle and blood circulation in humans, establishing MOTS-c as an exercise-induced factor. At the molecular level, MOTS-c regulates nuclear genes related to metabolism and protein quality control (proteostasis), directly affects skeletal muscle metabolism, and helps muscle cells (myoblasts) adapt to metabolic stress.
Reynolds, Joseph C; Lai, Rochelle W; Woodhead, Jonathan S T; Joly, James H; Mitchell, Cameron J; Cameron-Smith, David; Lu, Ryan; Cohen, Pinchas; Graham, Nicholas A; Benayoun, Bérénice A; Merry, Troy L; Lee, Changhan · Basic Science (Animal + Human)
RPEP-05724 · 2021Localized enzyme-assisted self-assembly produced peptide-based supramolecular hydrogel coatings whose properties could be precisely tuned by varying hyaluronic acid concentration. Coating thickness ranged from 18 µm (at 10 mg/mL HA) to 41 µm (at 2 mg/mL HA), while the elastic modulus decreased from 2 kPa to 0.2 kPa as HA concentration increased.
Higher HA concentrations caused peptide nanofibers to collapse into larger microstructures, fundamentally altering the internal architecture of the hydrogel. Despite these structural changes, all formulations supported NIH 3T3 fibroblast viability and adhesion.
Rodon Fores, Jennifer; Bigo-Simon, Alexis; Wagner, Déborah; Payrastre, Mathilde; Damestoy, Camille; Blandin, Lucille; Boulmedais, Fouzia; Kelber, Julien; Schmutz, Marc; Rabineau, Morgane; Criado-Gonzalez, Miryam; Schaaf, Pierre; Jierry, Loïc · In Vitro
RPEP-05731 · 2021After an initial 20-week period where all participants lost an average of 10.6% body weight on semaglutide 2.4 mg, those who continued semaglutide lost an additional 7.9% body weight over 48 more weeks, while those switched to placebo regained 6.9%. The net difference was a staggering 14.8 percentage points between continuing and stopping the drug.
Beyond weight, continuing semaglutide also produced significant improvements in waist circumference (-9.7 cm vs placebo), systolic blood pressure (-3.9 mmHg vs placebo), and physical functioning scores. By the end of the full 68-week period, people who stayed on semaglutide had lost a total of approximately 17.4% of their starting body weight.
Gastrointestinal side effects occurred in 49.1% of those continuing semaglutide vs 26.1% on placebo, but dropout rates due to adverse events were similar (2.4% vs 2.2%). Study completion was remarkably high at 98%.
Rubino, Domenica; Abrahamsson, Niclas; Davies, Melanie; Hesse, Dan; Greenway, Frank L; Jensen, Camilla; Lingvay, Ildiko; Mosenzon, Ofri; Rosenstock, Julio; Rubio, Miguel A; Rudofsky, Gottfried; Tadayon, Sayeh; Wadden, Thomas A; Dicker, Dror · Randomized Controlled Trial
RPEP-05744 · 2021Two major peptide-based antimicrobial strategies are emerging. First, novel modified antimicrobial peptides (AMPs) are being engineered to overcome traditional AMP limitations like instability and toxicity while maintaining antibacterial activity. Second, cell-penetrating peptides (CPPs) conjugated to phosphorodiamidate morpholino oligomers (PPMOs) can deliver gene-specific antimicrobials directly into gram-negative bacteria. PPMOs maintain activity against multidrug-resistant strains and show effectiveness in biofilm settings — two critical advantages over conventional antibiotics. Resistance development to these peptide approaches appears slower than to traditional antibiotics.
Schafer, Morgan E; Browne, Hailee; Goldberg, Joanna B; Greenberg, David E · Review
RPEP-05747 · 2021Four melanoma cell lines (MUG Mel3) were established from pigmented and non-pigmented sections of a lymph node metastasis from a pregnant patient, cultured under different conditions. Each line exhibited distinct phenotypic, genotypic, and tumorigenic properties — all carrying BRAF mutations — demonstrating melanoma's inherent heterogeneity.
Synthetic human lactoferricin-derived peptides were tested against all four cell lines and showed effective anti-tumor activity across the board. This is significant because the peptides worked despite the considerable heterogeneity between cell lines, suggesting broad applicability against diverse melanoma cell populations.
Schrom, Silke; Hebesberger, Thomas; Wallner, Stefanie Angela; Anders, Ines; Richtig, Erika; Brandl, Waltraud; Hirschmugl, Birgit; Garofalo, Mariangela; Bernecker, Claudia; Schlenke, Peter; Kashofer, Karl; Wadsack, Christian; Aigelsreiter, Ariane; Heitzer, Ellen; Riedl, Sabrina; Zweytick, Dagmar; Kretschmer, Nadine; Richtig, Georg; Rinner, Beate · In Vitro
RPEP-05748 · 2021BPC-157 promotes wound healing across virtually all tissue types through vessel regulation, clot management, and rapid gene expression activation, effective at both µg and ng doses via oral or injectable routes.
Seiwerth, Sven; Milavic, Marija; Vukojevic, Jaksa; Gojkovic, Slaven; Krezic, Ivan; Vuletic, Lovorka Batelja; Pavlov, Katarina Horvat; Petrovic, Andrea; Sikiric, Suncana; Vranes, Hrvoje; Prtoric, Andreja; Zizek, Helena; Durasin, Tajana; Dobric, Ivan; Staresinic, Mario; Strbe, Sanja; Knezevic, Mario; Sola, Marija; Kokot, Antonio; Sever, Marko; Lovric, Eva; Skrtic, Anita; Blagaic, Alenka Boban; Sikiric, Predrag · Review