RPEP-06371 · 2022Kisspeptin has been established as the master regulator of mammalian reproduction, controlling both puberty onset and ongoing fertility. Human studies confirm that kisspeptin administration stimulates physiological reproductive hormone secretion in healthy men and women, as well as in patients with common reproductive disorders.
Neurokinin B (NKB), which works alongside kisspeptin in KNDy neurons (kisspeptin/neurokinin B/dynorphin neurons), has emerged as a therapeutic target for menopausal hot flashes, endometriosis, and uterine fibroids. NKB receptor antagonists are being developed as treatments for these conditions. Together, kisspeptin and NKB represent two complementary peptide-based approaches to managing reproductive health.
Mills, Edouard G; Dhillo, Waljit S ·
RPEP-06372 · 2022Researchers conducted the first detailed structure-activity analysis of mitochondria-targeted tetrapeptides — the class that includes SS-31 (elamipretide). They compared four peptide analogs that differ in their aromatic amino acid composition and sequence order. Using NMR and molecular dynamics, they produced the first structural models of this compound class, revealing that all analogs except SS-31 form compact reverse turn conformations when bound to membranes.
All four peptides bound cardiolipin-containing membranes (a key mitochondrial lipid), reached mitochondria in cell culture, and showed pharmacological activity in stress models. However, they differed significantly in membrane interactions, effects on membrane surface charge, and ability to restore mitochondrial function. The tryptophan-containing analog SPN10 showed the strongest membrane effects and greatest cell protection, suggesting tryptophan side chains may be optimal for this class of therapeutics.
Mitchell, Wayne; Tamucci, Jeffrey D; Ng, Emery L; Liu, Shaoyi; Birk, Alexander V; Szeto, Hazel H; May, Eric R; Alexandrescu, Andrei T; Alder, Nathan N · Original Research
RPEP-06374 · 2022Substance P increased mRNA expression of MMP-2, MMP-9, VEGF, and VEGFR in A2780 ovarian cancer cells, promoting cell migration (confirmed by scratch assay) and angiogenic signaling. Blocking the NK1R receptor with aprepitant suppressed all of these Substance P-induced effects, reducing both migration-related and angiogenesis-related gene expression.
The findings establish a mechanistic link between the SP/NK1R signaling system and two key processes in ovarian cancer metastasis: cell migration (via matrix metalloproteinases) and new blood vessel formation (via VEGF/VEGFR pathway).
Momen Razmgah, Maryam; Ghahremanloo, Atefeh; Javid, Hossein; AlAlikhan, Abbas; Afshari, Amir-R; Hashemy, Seyed Isaac ·
RPEP-06378 · 2022Across all four trials, semaglutide significantly reduced hsCRP versus comparators with estimated treatment ratios of 0.70-0.76 (meaning 24-30% greater reduction; p < 0.05). This held true when analyzed by clinical cutoffs and by baseline hsCRP tertiles, showing benefit across the inflammation spectrum.
Mediation analysis revealed that changes in HbA1c and body weight accounted for only 20.6-61.8% of semaglutide's CRP-lowering effect, suggesting a substantial direct anti-inflammatory action. In PIONEER 5 (the chronic kidney disease trial), the CRP reduction was not statistically significant versus comparators, indicating the anti-inflammatory effect may be attenuated in CKD. Baseline hsCRP ranged from 2.7-3.0 mg/L across trials, placing this population at elevated cardiovascular risk.
Mosenzon, Ofri; Capehorn, Matthew S; De Remigis, Alessandra; Rasmussen, Søren; Weimers, Petra; Rosenstock, Julio ·
RPEP-06384 · 2022Cerebrolysin, a peptide preparation derived from pig brain tissue, significantly reduced anxiety in patients with moderate and severe traumatic brain injury (TBI) compared to placebo. Statistically significant differences in HADS-Anxiety scores were found at both the second and third follow-up visits, with a large effect size of 0.73.
The study also identified correlations between anxiety/depression scores and other neuropsychological measures, suggesting that post-TBI mental health is connected to cognitive and motor recovery. The patient sample had a mean age of 45.3, was primarily male, and had a 24-hour Glasgow Coma Scale mean of 12.67 (indicating moderate-to-severe injury).
Mureșanu, Ioana Anamaria; Grad, Diana Alecsandra; Mureșanu, Dafin Fior; Hapca, Elian; Benedek, Irina; Jemna, Nicoleta; Strilciuc, Ștefan; Popescu, Bogdan Ovidiu; Perju-Dumbravă, Lăcrămioara; Cherecheș, Răzvan Mircea · Secondary Analysis
RPEP-06387 · 2022Researchers grafted key hydrophobic amino acids (phenylalanine, tryptophan, leucine) onto a cell-penetrating peptide scaffold (CADY2) to create membrane-permeable protein-protein interaction inhibitors. While the resulting peptides (CADY-3FWL and CADY-10FWL) successfully killed cancer cells through apoptosis, they did not bind to their intended target (HDM2). Instead, proteomic analysis revealed they bound nesprin-2, a protein involved in shuttling β-catenin into the cell nucleus.
The peptides reduced nuclear β-catenin localization and decreased expression of anti-apoptotic genes in the Wnt signaling pathway — an unexpected but potentially valuable anticancer mechanism.
Nagano, Yuki; Arafiles, Jan Vincent V; Kuwata, Keiko; Kawaguchi, Yoshimasa; Imanishi, Miki; Hirose, Hisaaki; Futaki, Shiroh ·
RPEP-06391 · 2022Affinity-based release strategies incorporate reversible molecular interactions into peptide hydrogel networks that bind and gradually release therapeutic cargo. These interactions can be tuned to control drug release profiles, meeting specific pharmacokinetic requirements. The review identifies this as an underexplored but promising approach in peptide hydrogels, which offer advantages over polymer-based systems including biocompatibility and biodegradability inherent to peptide materials.
Nambiar, Monessha; Schneider, Joel P ·
RPEP-06398 · 2022Anamorelin led to a significant increase in lean body mass index in clinical trials.
Nishie, Kenichi; Sato, Seiichi; Hanaoka, Masayuki ·
RPEP-06400 · 2022A 50-year-old woman with type 2 diabetes, obesity, and schizophrenia had poorly controlled HbA1c (8.0-10.2%) on multiple diabetes medications including dulaglutide, with repeated hospitalizations for suicide attempts via drug overdose. Switching to semaglutide 0.5 mg with multidisciplinary support (including cognitive-behavioral therapy) resulted in: patient-reported hunger suppression, sustained HbA1c improvement, and sustained body weight reduction maintained for 6 months. Semaglutide was remarkably more effective than dulaglutide in this case.
Noda, Kaoru; Kato, Takehiro; Nomura, Nao; Sakai, Mayu; Kubota, Sodai; Hirose, Tokuyuki; Liu, Yanyan; Takahashi, Yoshihiro; Takao, Ken; Mizuno, Masami; Hirota, Takuo; Suwa, Tetsuya; Horikawa, Yukio; Yabe, Daisuke ·
RPEP-06402 · 2022CCK in mammals and sulfakinins (SKs) in invertebrates share deeply conserved functional roles that extend far beyond gut signaling. In mammals, CCK is produced by both gut endocrine cells and brain neurons and regulates gallbladder contraction, pancreatic enzyme secretion, satiety, reward, anxiety, aggression, and sexual behavior.
In Drosophila, a set of just eight SK-expressing brain neurons integrates internal state and external stimuli to coordinate competing behavioral outputs: they diminish sugar gustation, induce satiety, reduce feeding, suppress sex drive in males, and increase aggression. This demonstrates that a single neuropeptide system can arbitrate between multiple survival-critical behaviors depending on context. While the functional roles appear conserved between flies and mammals, the underlying neural mechanisms differ.
Nässel, Dick R; Wu, Shun-Fan ·
RPEP-06409 · 2022The review highlights that peptide-based supramolecular hydrogels have made significant advances in drug delivery through several key developments: improved peptide self-assembly techniques that create more stable gel structures, functionalization strategies that enable targeted delivery, bioadhesive properties that keep gels in place at treatment sites, and enhanced drug release profiles that can be tuned for sustained or triggered release.
Particularly notable progress has been made in anticancer drug loading and release, where different hydrogel matrix designs allow controlled delivery of chemotherapy agents directly to tumor sites, potentially reducing the systemic toxicity associated with conventional chemotherapy.
Oliveira, Carlos B P; Gomes, Valéria; Ferreira, Paula M T; Martins, José A; Jervis, Peter J ·
RPEP-06420 · 2022The synthetic nano-chaperone improved cellular uptake and bioavailability of peptides, effectively inhibiting cancer growth.
Park, Il-Soo; Kim, Seongchan; Yim, Yeajee; Park, Ginam; Choi, Jinahn; Won, Cheolhee; Min, Dal-Hee ·
RPEP-06434 · 2022In 259 T2D patients over 26 weeks, higher-dose tirzepatide (vs dulaglutide and placebo):
- Reduced branched-chain amino acids (BCAAs) and their catabolic products (glutamate, 3-hydroxyisobutyrate, branched-chain ketoacids)
- Decreased 2-hydroxybutyrate — a marker of metabolic stress
- Significantly lowered triglycerides and diglycerides, particularly shorter, highly saturated species
- Changes were directly proportional to reductions in HbA1c, HOMA2-IR (insulin resistance), and proinsulin levels
- Improvements were significantly larger with tirzepatide than dulaglutide
- Effects were only partially attributable to weight loss, suggesting direct metabolic modulation
- Changes consistent with improved metabolic health and reduced T2D risk markers
Pirro, Valentina; Roth, Kenneth D; Lin, Yanzhu; Willency, Jill A; Milligan, Paul L; Wilson, Jonathan M; Ruotolo, Giacomo; Haupt, Axel; Newgard, Christopher B; Duffin, Kevin L ·
RPEP-06440 · 2022In a double-blind, placebo-controlled, crossover trial with 31 healthy adult men, a single 24 IU dose of intranasal oxytocin did not modulate neural responses to social (faces) versus non-social (houses) stimuli. Frequency-tagging EEG clearly detected robust stimulus-specific neural responses — face processing was strongest in lateral occipito-temporal regions and house processing in medial occipital regions — confirming the methodology worked.
However, oxytocin did not enhance social processing, nor did it increase general information salience. Bayesian analyses formally confirmed these null findings, providing evidence of absence rather than merely absence of evidence. The researchers suggested that the neurotypical participants' baseline ceiling-level performance and the personal irrelevance of the stimuli may have prevented detection of any oxytocin effect.
Qiao, Zhiling; Van der Donck, Stephanie; Moerkerke, Matthijs; Dlhosova, Tereza; Vettori, Sofie; Dzhelyova, Milena; van Winkel, Ruud; Alaerts, Kaat; Boets, Bart ·
RPEP-06449 · 2022Systematic single amino acid substitutions at the N-terminal, mid-chain, and C-terminal positions of Smp24 revealed position-dependent structure-function relationships:
- **Increased charge (N-, mid-, C-termini)**: Enhanced antimicrobial activity against Gram-negative bacteria across all positions
- **Increased N-terminal hydrophobicity**: Reduced haemolysis and cytotoxicity — a beneficial safety improvement
- **Increased mid-chain hydrophobicity**: Reduced both antimicrobial and cytotoxic activity — a neutral-to-detrimental change
Several modified peptides achieved enhanced therapeutic indices compared to native Smp24, with improved antibacterial selectivity that makes them more promising as potential antibiotic drug candidates.
Rawson, Kirstie M; Lacey, Melissa M; Strong, Peter N; Miller, Keith ·
RPEP-06451 · 2022Among 164 eligible studies from a pool of 265 identified, metformin at dosages of 1500-2550 mg/day emerged as the most effective and cost-efficient non-hormonal treatment for restoring menstrual frequency in overweight adolescents with PCOS, also improving insulin sensitivity. GLP-1 receptor agonists showed effectiveness in menstrual cycle regulation. Supplements including chromium picolinate and myo-inositol also demonstrated some benefits. However, only four placebo-controlled studies were identified, with varying inclusion and exclusion criteria, highlighting the limited evidence base.
Reiser, Elisabeth; Lanbach, Julia; Böttcher, Bettina; Toth, Bettina ·
RPEP-06456 · 2022BT8009, a bicycle toxin conjugate consisting of a Nectin-4-binding bicyclic peptide linked to MMAE, demonstrated significant antitumor activity across multiple preclinical cancer models. It showed superior or equivalent activity to an enfortumab vedotin analog. Key pharmacokinetic advantages include rapid tissue diffusion and tumor penetration due to its small size, and renal elimination with a half-life of 1-2 hours in rats and non-human primates — dramatically shorter than antibody-based approaches, which may reduce systemic toxicity exposure.
Rigby, Michael; Bennett, Gavin; Chen, Liuhong; Mudd, Gemma E; Harrison, Helen; Beswick, Paul J; Van Rietschoten, Katerine; Watcham, Sophie M; Scott, Heather S; Brown, Amy N; Park, Peter U; Campbell, Carly; Haines, Eric; Lahdenranta, Johanna; Skynner, Michael J; Jeffrey, Phil; Keen, Nicholas; Lee, Kevin ·
RPEP-06458 · 2022The ghrelin receptor (GHSR1a) does far more than just trigger hunger. It physically pairs up (heterodimerizes) with at least six other brain receptors — dopamine D1 and D2, serotonin 2C, orexin, oxytocin, and melanocortin 3 receptors — and each pairing changes how both receptors signal. This receptor cross-talk explains how ghrelin influences such a wide range of functions: hunger, reward-seeking, memory, gut motility, blood sugar control, heart function, and neuroprotection.
Notably, GHSR1a has high constitutive activity at some sites, meaning it sends signals even without ghrelin present. This constitutive signaling may be therapeutically important.
Ringuet, Mitchell Ty; Furness, John Barton; Furness, Sebastian George Barton · Review
RPEP-06459 · 2022The review identifies several critical challenges in neoantigen cancer vaccine development:
- Bioinformatic algorithms predict hundreds of potential neoepitopes per tumor, but most are not immunogenic
- Few neoantigen cancer vaccines have generated strong epitope-specific T cell responses in vivo, despite promising preclinical data
- HLA diversity means each patient's immune system recognizes different peptides, requiring fully personalized vaccines
- Intratumoral heterogeneity of mutations means targeting one neoantigen may allow resistant clones to escape
- Suboptimal delivery and immune activation strategies may explain the gap between preclinical and clinical results
Roesler, Alexander S; Anderson, Karen S ·
RPEP-06466 · 2022The review outlines AMH's key clinical roles:
• AMH is produced by granulosa cells of growing follicles before they become FSH-dependent, making it a direct marker of the ovarian follicle pool
• AMH serum concentration strongly correlates with ovarian reserve quantity and reflects ovulation potential
• In males, Sertoli cells produce high AMH levels that suppress Müllerian duct development during embryonic sex determination, maintaining high levels until puberty
• In females, AMH production begins in the second half of fetal life, declines through reproductive years, drops severely at menopause, and eventually becomes undetectable
• Clinical applications include PCOS diagnosis and pathogenesis assessment, artificial reproductive technology (IVF) planning, and prediction of menopause or premature ovarian failure
Russell, Nicole; Gilmore, Andrea; Roudebush, William E ·
RPEP-06471 · 2022The review found that CPPs have been successfully used in both laboratory and animal studies to deliver therapeutic peptides and proteins that target three key disease processes: oxidative stress (cellular damage from reactive molecules), inflammatory response (the immune system's overreaction), and apoptosis (programmed cell death).
However, the authors identified four fundamental obstacles preventing clinical use: CPPs lack specificity (they enter healthy and diseased cells alike), they are unstable in the body (enzymes break them down), they may be toxic at effective doses, and they can trigger immune responses. The review concludes that more research is needed to overcome these limitations before CPP-mediated delivery can be used in patients.
Sadeghian, Issa; Heidari, Reza; Raee, Mohammad Javad; Negahdaripour, Manica · Review
RPEP-06481 · 2022The reduced (unfolded) form of cryptdin-4 (Crp4red) killed both commensal and non-commensal bacteria, while the oxidized (folded) form (Crp4ox) only killed non-commensal bacteria. The key difference was hydrophobicity — Crp4red's exposed hydrophobic regions allowed it to insert deeply into bacterial membranes and disrupt them.
When researchers blocked the cysteine thiol groups with N-ethylmaleimide (NEM-Crp4), the resulting peptide mimicked Crp4red's high hydrophobicity and also killed commensal bacteria. Conversely, blocking electrostatic interactions abolished killing by both forms, confirming that initial membrane binding via electrostatic attraction is required before hydrophobic insertion can occur. Liposome leakage assays using lipids from commensal bacteria confirmed that membrane disruption correlated directly with bactericidal activity.
Sato, Yuji; Wang, Yi; Song, Yuchi; Geng, Weiming; Yan, Shaonan; Nakamura, Kiminori; Kikukawa, Takashi; Demura, Makoto; Ayabe, Tokiyoshi; Aizawa, Tomoyasu ·
RPEP-06483 · 2022Thymosin β4 knockout mice developed macrothrombocytopenia (low platelet count with mildly enlarged platelets) due to defective proplatelet formation from megakaryocytes, both in vitro and in vivo. The remaining platelets had markedly decreased G-actin and increased F-actin levels, disrupting the normal actin equilibrium.
This actin imbalance produced paradoxical effects: accelerated platelet spreading on fibrinogen and faster clot retraction, but impaired platelet activation through the glycoprotein VI collagen receptor pathway due to defective ITAM signaling. The net result was impaired aggregate formation under flow conditions, protection from occlusive arterial thrombus formation in vivo, and increased tail bleeding times — demonstrating that thymosin β4 is essential for both platelet production and functional thrombus stability.
Scheller, Inga; Beck, Sarah; Göb, Vanessa; Gross, Carina; Neagoe, Raluca A I; Aurbach, Katja; Bender, Markus; Stegner, David; Nagy, Zoltan; Nieswandt, Bernhard ·
RPEP-06484 · 2022The native hydrophobic residues in ponericin L1 were uniformly replaced with either leucine, isoleucine, phenylalanine, alanine, or valine. Several variants showed enhanced antimicrobial activity compared to the parent peptide, while others lost activity entirely.
Most notably, the valine variant lost all antimicrobial activity and all ability to interact with lipid bilayers. The variants showed varying degrees of membrane interaction, with some responses depending on the lipid composition of the target membrane. Spectroscopic analysis revealed that the substitutions altered both secondary structure and membrane binding behavior. The results demonstrate that peptide secondary structure, amino acid composition, and hydrophobicity must be carefully balanced — getting any one factor wrong can result in either non-specific binding or complete loss of function.
Schifano, Nicholas P; Caputo, Gregory A ·
RPEP-06485 · 2022PATAS is a stapled peptide derived from the kinase domain of PKCα that disrupts the ALMS1-PKCα protein interaction in adipocytes. The mechanistic pathway was identified through studying Alström syndrome, an ultrarare genetic disorder caused by ALMS1 inactivation that results in severe insulin resistance.
In cultured human adipocytes, PATAS triggered insulin-independent glucose absorption, de novo lipogenesis (fat synthesis from glucose), and cellular glucose utilization — effectively bypassing the insulin signaling pathway.
In vivo in rodent models, PATAS reduced whole-body insulin resistance and improved glucose intolerance, fasting glucose levels, liver steatosis (fatty liver), and liver fibrosis. Importantly, the study also showed that reactivating ALMS1 specifically in adipocytes reversed all these metabolic phenotypes, confirming that the adipocyte is the key therapeutic target.
Schreyer, Edwige; Obringer, Cathy; Messaddeq, Nadia; Kieffer, Bruno; Zimmet, Paul; Fleming, Alexander; Geberhiwot, Tarekegn; Marion, Vincent ·
RPEP-06487 · 2022Using millisecond time-resolved synchrotron small-angle X-ray scattering, researchers captured the real-time response of E. coli to lactoferricin-derived AMPs across length scales from whole cells down to lipid packing. Key findings:
1. The peptides permeabilized the cytosolic membrane in less than 3 seconds — much faster than previously considered.
2. Final intracellular peptide concentrations reached ~80–100 mM, suggesting efficient obstruction of physiologically important processes as the primary killing mechanism.
3. Membrane damage and leakage occurred even at sublethal concentrations, showing that membrane permeabilization is a necessary but not sufficient condition for killing.
4. The most efficient peptide studied excelled in both speed of membrane permeabilization and lowest intracellular concentration needed to inhibit bacterial growth.
Semeraro, Enrico F; Marx, Lisa; Mandl, Johannes; Letofsky-Papst, Ilse; Mayrhofer, Claudia; Frewein, Moritz P K; Scott, Haden L; Prévost, Sylvain; Bergler, Helmut; Lohner, Karl; Pabst, Georg ·
RPEP-06489 · 2022Anti-CGRP monoclonal antibodies represent a paradigm shift in migraine treatment — the first drugs designed specifically around migraine pathophysiology. These drugs target calcitonin gene-related peptide (CGRP), a neuropeptide that plays a central role in causing migraine attacks. The review concludes that anti-CGRP mAbs are highly effective but face real-world challenges: high cost, limited long-term experience, and the need for multidisciplinary teams to identify which patients will benefit most.
The review emphasizes that proper patient selection and cost-effective prescribing strategies are essential as these drugs move from clinical trials into routine practice.
Serra López-Matencio, José María; Gago-Veiga, Ana Beatriz; Gómez, Manuel; Alañón Plaza, Estefanía; Mejía, Gina Paola; González-Gay, Miguel Ángel; Castañeda, Santos · Review
RPEP-06491 · 2022A personalized neoantigen nanovaccine combined with anti-PD-1 antibody therapy resulted in an overall survival of 10.5 months in an advanced pancreatic cancer patient who had relapsed on third-line treatment.
The patient developed peptide-specific T-cell responses against 9 of the 12 vaccine peptides, confirmed by IFN-γ ELISPOT and intracellular cytokine staining. These robust and sustained neoantigen-specific T cell responses suggest the vaccine successfully activated targeted anti-tumor immunity.
Shao, Jie; Liu, Qin; Shen, Jie; Qian, Xiaoping; Yan, Jing; Zhu, Yahui; Qiu, Xin; Lu, Changchang; Cen, Lanqi; Tian, Manman; Du, Juan; Liu, Baorui ·
RPEP-06492 · 2022Key results from the composite hydrogel study:
- Differential peptide doping into TO-NFC hydrogel tuned surface hydrophobicity, microporosity, and mechanical stiffness
- Different cellular responses observed at varying TO-NFC:Nap-FEFK ratios
- 10:1 (w/w) ratio showed enhanced cellular survival and proliferation in 2D culture
- 10:1 composite matched Matrigel performance in 3D cell culture conditions
- No significant inflammatory response in Raw macrophage cells
- Scaffolds supported immune cell survival and proliferation
- Demonstrates multicomponent self-assembly as a viable approach for ECM-mimicking biomaterials
Sharma, Pooja; Pal, Vijay K; Kaur, Harsimran; Roy, Sangita ·
RPEP-06495 · 2022Nv-CATH (sequence: NCNFLCKVKQRLRSVSSTSHIGMAIPRPRG), a 30-residue cathelicidin peptide from frog skin, demonstrated:
- Broad-spectrum antimicrobial activity against both Gram-positive and Gram-negative bacteria
- Significant protection of mice from lethal S. aureus infections
- Suppression of harmful inflammatory responses by reducing production of NO, IL-6, TNF-α, and IL-1β
- Anti-inflammatory action through the NF-κB-NLRP3 and MAPK signaling pathways (confirmed both in vitro and in vivo)
- Immune cell recruitment by stimulating CXCL1, CXCL2, and CCL2 chemokine production in macrophages
- Enhanced immune cell killing by modestly promoting neutrophil phagocytosis and NET formation
The dual antimicrobial-immunomodulatory mechanism sets this peptide apart from conventional antibiotics.
Shi, Jie; Wu, Jing; Chen, Qian; Shen, Yan; Mi, Kai; Yang, Hailong; Mu, Lixian ·
RPEP-06501 · 2022Food-derived peptides from diverse sources — milk, meat, fish, eggs, soy, rice, wheat, mushrooms, and pumpkins — can lower blood pressure through multiple mechanisms targeting the renin-angiotensin system (RAS). These peptides inhibit both renin and angiotensin-converting enzyme (ACE), the two key enzymes that raise blood pressure.
Beyond enzyme inhibition, food-derived ACE inhibitory peptides also enhance nitric oxide production in blood vessel walls, promoting vasodilation (blood vessel relaxation). Additionally, they can block the interaction between angiotensin II and its receptor, providing a third mechanism for blood pressure reduction.
The review surveys the breadth of food sources containing antihypertensive peptides and their various applications for managing cardiovascular disease.
Shukla, Pratik; Chopada, Keval; Sakure, Amar; Hati, Subrota · Review
RPEP-06504 · 2022This review summarizes weight loss results from three major semaglutide clinical trial programs: SUSTAIN (1.0 mg weekly injection for type 2 diabetes), PIONEER (oral semaglutide for type 2 diabetes), and STEP (2.4 mg weekly injection for obesity without diabetes). All three programs demonstrated that semaglutide — both injected and oral — produced superior weight loss compared to placebo and other antidiabetic medications. These results collectively supported the FDA approval of Wegovy (semaglutide 2.4 mg) as a dedicated weight loss medication.
Singh, Gurdeep; Krauthamer, Matthew; Bjalme-Evans, Meghan · Review
RPEP-06508 · 2022GK-19 demonstrated broad-spectrum antimicrobial activity against five bacterial species (including Gram-positive and Gram-negative) and three fungal species by disrupting microbial cell membranes. Key advantages over the parent scorpion peptide AamAP1:
- Negligible toxicity to mammalian cells (the original AamAP1 was strongly toxic)
- Low hemolytic activity (does not destroy red blood cells)
- High stability in blood plasma
In scalded mouse models with skin and soft tissue infections, GK-19 showed significant antimicrobial effects and improved wound healing when infections were induced by either MRSA (methicillin-resistant Staphylococcus aureus) or Candida albicans.
Song, Chenghua; Wen, Ruichao; Zhou, Jiaxuan; Zeng, Xiaoyan; Kou, Zi; Zhang, Jia; Wang, Tao; Chang, Pengkang; Lv, Yi; Wu, Rongqian ·
RPEP-06510 · 2022Injecting vitamin D directly into common warts (verruca vulgaris) significantly increased expression of the antimicrobial peptide LL-37 (cathelicidin) in the skin (p=0.003). Of 20 patients treated, 40% showed complete wart clearance and 35% showed partial response. Warts that cleared completely had the highest LL-37 expression (p=0.022).
After treatment, the skin also showed decreased epidermal thickness and reduced inflammatory cell density, indicating the immune response was shifting from chronic inflammation toward effective viral clearance driven by LL-37.
Sorour, Neveen E; Elesawy, Fatma M; Abdou, Asmaa G; Abdelazeem, Sara E; Akl, Essam M · Interventional Clinical
RPEP-06517 · 2022The review identifies a 'triumvirate' of hypothalamic arcuate nucleus neurons — kisspeptin (Kiss1), pro-opiomelanocortin (POMC), and agouti-related peptide/neuropeptide Y (AgRP/NPY) — that arise from a common progenitor pool and are all regulated by estrogen (specifically 17β-estradiol).
Kiss1 neurons are the most sensitive to estrogen of the three populations and are critical for controlling gonadotropin-releasing hormone (GnRH) neurons, which drive the luteinizing hormone pulses and surges needed for ovulation. A key finding highlighted is that Kiss1 and POMC neurons collaborate to inhibit AgRP neurons, reducing food motivation. This provides a mechanistic explanation for how the brain prioritizes reproductive function over appetite during fertile periods — estrogen essentially tells the brain 'conditions are right for reproduction, reduce food-seeking behavior.'
Stincic, Todd L; Kelly, Martin J ·
RPEP-06518 · 2022Thymosin beta-4 at 600 ng/mL produced multiple improvements in diabetic endothelial cells:
• Significantly upregulated AKT activity and Bcl-XL protein expression (pro-survival pathways)
• Enhanced cell viability and proliferation
• Reduced cellular senescence (aging)
• Decreased secretion of endothelin-1 (a vasoconstrictor) and MMP-1 (a tissue-degrading enzyme)
• Improved angiogenic (blood vessel-forming) potency when dia-hiPSC-ECs were used to treat ischemic limb disease in type 2 diabetic mice
However, Tβ4 did NOT improve mitochondrial membrane potential, glycine homeostasis, or reduce ICAM-1 protein expression — showing its effects are specific to certain pathways rather than a universal fix for diabetic endothelial dysfunction.
Su, Liping; Kong, Xiaocen; Loo, Szejie; Gao, Yu; Liu, Bingli; Su, Xiaofei; Dalan, Rinkoo; Ma, Jianhua; Ye, Lei ·
RPEP-06520 · 2022Researchers created exosomes (tiny cell-derived vesicles) loaded with high levels of the antimicrobial peptide LL-37 by treating immune cells with vitamin D3 and a CYP24A1 inhibitor. These engineered exosomes contained significantly more LL-37 than exosomes from untreated cells or genetically transfected cells.
The LL-37-loaded exosomes performed three functions simultaneously: they killed bacteria, promoted blood vessel formation (endothelial tube formation), and enhanced skin cell growth and migration. When embedded in electrospun nanofiber matrices for slow release, they became a multi-functional wound healing platform.
Su, Yajuan; Sharma, Navatha Shree; John, Johnson V; Ganguli-Indra, Gitali; Indra, Arup K; Gombart, Adrian F; Xie, Jingwei · In Vitro Laboratory Study
RPEP-06523 · 2022Topical benvitimod (1% and 0.5%) reduced redness scores, redness areas, and dermal inflammatory cell infiltrates in LL-37-induced rosacea-like eruptions in BALB/c mice. In both the mouse model and LL-37-treated HaCaT cells, AhR activation decreased elevated TLR2 expression and suppressed four inflammatory chemokines: CCL5, CXCL9, CXCL10, and CXCL11. Over-expressing TLR2 in HaCaT cells further enhanced chemokine release, confirming TLR2 as the key pathway. Benvitimod (10 μM) reduced gene expression at 8 hours and protein expression at 24 hours in LL-37-treated cells.
Sun, Yan; Chen, LiangHong; Wang, HeXiao; Zhu, PeiYao; Jiang, ShiBin; Qi, RuiQun; Wu, Yan; Gao, XingHua ·
RPEP-06524 · 2022Biphenyl-tripeptide molecules self-assembled into nanofiber hydrogels at ultra-low concentrations (about 0.27 wt%) with mechanical strength ranging from 0.7 to 13.8 kPa. The strongest variant (BPAA-AFF) formed 10 nm nanofibers with a storage modulus of 13.8 kPa and a morphology resembling natural extracellular matrix.
These hydrogels demonstrated excellent biocompatibility, supporting cell adhesion and proliferation. When tested with cartilage cells, they specifically enhanced the expression of cartilage-related genes and promoted cartilage matrix production, suggesting strong potential for cartilage tissue engineering.
Sun, Yong; Li, Xing; Zhao, Mingda; Chen, Yafang; Xu, Yang; Wang, Kefeng; Bian, Shaoquan; Jiang, Qing; Fan, Yujiang; Zhang, Xingdong ·
RPEP-06526 · 2022Clinical trials and population-based studies have established safety regarding pancreatic carcinoma for incretin-based therapies. However, animal models have inconsistently shown low-grade chronic pancreatitis with these medications, and some human studies have reported acute pancreatitis. Since chronic pancreatitis is a known risk factor for pancreatic cancer, the pathophysiological pathway from drug-induced inflammation to cancer remains a theoretical concern even though epidemiological evidence has not confirmed it.
Suryadevara, Varun; Roy, Ayan; Sahoo, Jayaprakash; Kamalanathan, Sadishkumar; Naik, Dukhabandhu; Mohan, Pazhanivel; Kalayarasan, Raja ·
RPEP-06536 · 2022When researchers used CRISPR gene editing to completely knock out the vasopressin V1a receptor in Syrian hamsters, the results were the opposite of what decades of research predicted. Instead of becoming less social and less aggressive, the knockout hamsters were substantially more social (more flank-marking communication) and more aggressive toward same-sex peers than normal hamsters.
Additionally, the typical sex differences in aggression disappeared — both male and female knockouts showed elevated aggression. The knockout was confirmed to be complete: no V1a receptor binding was detected anywhere in the brain, and the animals showed no response to vasopressin or V1a-specific drugs.
These paradoxical findings suggest that the vasopressin V1a receptor may actually inhibit social behavior rather than promote it — flipping the long-held assumption about how this peptide system works.
Taylor, Jack H; Walton, James C; McCann, Katharine E; Norvelle, Alisa; Liu, Qian; Vander Velden, Jacob W; Borland, Johnathan M; Hart, Michael; Jin, Chengliu; Huhman, Kim L; Cox, Daniel N; Albers, H Elliott · Animal Study
RPEP-06541 · 2022Self-assembled peptide hydrogels were successfully used to build a defrost sensor that uses turbidity (cloudiness) changes as a temperature indicator. The sensor irreversibly records whether a product has been thawed, preventing tampering or resetting.
By studying the gelation kinetics under different conditions, the researchers identified distinct stages of structural transitions in the hydrogel, allowing them to tune the sensor's response to specific temperature ranges and detection timeframes. The sensor can be stored at room temperature for extended periods before activation.
Tikhonova, Tatiana N; Cohen-Gerassi, Dana; Arnon, Zohar A; Efremov, Yuri; Timashev, Peter; Adler-Abramovich, Lihi; Shirshin, Evgeny A ·
RPEP-06546 · 2022Dextrose injections resulted in a 111% increase in synovial-fluid substance P at one week and a 65% decrease in neuropeptide Y at three months.
Topol, Gastón Andrés; Pestalardo, Ines Guerrero; Reeves, Kenneth Dean; Elias, Fernando; Steinmetz, Neven J; Cheng, An-Lin; Rabago, David ·
RPEP-06547 · 2022A split-peptide reporter system using ternary NanoLuc luciferase enables rapid, simple, and sensitive point-of-care diagnostics. Two small reporter peptides are attached to analyte-specific binding molecules. When both peptides bind their target, they come into proximity and reconstitute with a larger polypeptide to produce a bright bioluminescent signal — effectively turning target detection into a visible light signal.
The platform was demonstrated with two SARS-CoV-2 applications: detecting the N-antigen (active infection) and detecting anti-SARS-CoV-2 antibodies (immunity status). The system was lyophilized (freeze-dried) into a shelf-stable, all-in-one format that requires only adding the sample and reading with a handheld device.
Torio, Emily A; Ressler, Valerie T; Kincaid, Virginia A; Hurst, Robin; Hall, Mary P; Encell, Lance P; Zimmerman, Kristopher; Forsyth, Stuart K; Rehrauer, William M; Accola, Molly A; Hsu, Chia-Chang; Machleidt, Thomas; Dart, Melanie L · Experimental
RPEP-06556 · 2022At 12 weeks, the three highest dose groups of LY3437943 showed significant placebo-adjusted reductions in mean daily plasma glucose: -2.8, -3.1, and -2.9 mmol/L respectively. HbA1c decreased by -1.4%, -1.6%, and -1.2% (placebo-adjusted) at these doses. Bodyweight reduction was dose-dependent, reaching -8.96 kg (90% CI -11.16 to -6.75) in the highest dose group (3/6/9/12 mg escalation).
The peptide's pharmacokinetics were dose-proportional with a half-life of approximately 6 days, supporting once-weekly dosing. Treatment-emergent adverse events occurred in 63% of LY3437943 recipients (vs 54% placebo), primarily gastrointestinal. However, 29 of 72 participants discontinued prematurely across all groups.
Urva, Shweta; Coskun, Tamer; Loh, Mei Teng; Du, Yu; Thomas, Melissa K; Gurbuz, Sirel; Haupt, Axel; Benson, Charles T; Hernandez-Illas, Martha; D'Alessio, David A; Milicevic, Zvonko ·
RPEP-06557 · 2022The review establishes that the colon offers significant advantages for oral peptide delivery compared to upper GI segments: lower proteolytic enzyme activity, enhanced retention time, and conditions more favorable for peptide absorption. Nanomedicine strategies — including nanoparticles, liposomes, and other carrier systems — can protect peptides through the harsh upper GI environment and enable colon-specific release.
The authors classify therapeutic peptides and map them to appropriate nanomedicine delivery strategies, while also addressing the regulatory hurdles that currently slow clinical translation of these systems.
Vambhurkar, Ganesh; Amulya, Etikala; Sikder, Anupama; Shah, Saurabh; Famta, Paras; Khatri, Dharmendra Kumar; Singh, Shashi Bala; Srivastava, Saurabh ·
RPEP-06560 · 2022Among 3,497 migraine patients initiating self-injectable CGRP monoclonal antibodies alongside novel acute medications, the majority had chronic migraine (64.4–71.4%) and were already on both preventive and acute treatments. Most patients received combination therapy with both preventive and acute medications targeting the CGRP pathway — either both binding CGRP receptors (43.6–59.0%) or preventive medication binding CGRP ligands paired with acute medication binding CGRP receptors (34.9–51.9%).
Patients used both medications concurrently for an average of about 30 days, and prescribing patterns were consistent across different healthcare provider types.
Varnado, Oralee J; Hoyt, Maggie; Ye, Wenyu; Nicholson, Robert ·
RPEP-06567 · 2022Adding brush border membrane (BBM) enzymes to the standard INFOGEST digestion protocol revealed additional peptide cleavage sites beyond pancreatic digestion alone. BBM enzymes (amino- and carboxy-peptidases) reduced total peptide numbers but increased free amino acid concentrations, better approximating real digestion.
Comparing the in vitro peptidome with peptides from actual human jejunal aspirates, BBM addition allowed identification of peptides found in vivo — though neither model reproduced the full peptide diversity seen in human digestion. For six beta-casein peptides including beta-casomorphin-7, transepithelial transport through Caco-2 cells showed that N- and C-terminal residue identity was a key determinant of absorption rate.
Vivanco-Maroto, Santiaga María; Santos-Hernández, Marta; Sanchón, Javier; Picariello, Gianluca; Recio, Isidra; Miralles, Beatriz ·
RPEP-06569 · 2022After 52 weeks of once-weekly subcutaneous semaglutide added to metformin, 70% of type 2 diabetes patients with fatty liver disease showed improvement — reducing their liver steatosis by at least one ultrasound-assessed grade. The treatment produced significant decreases in body weight, insulin resistance, liver enzymes, and laboratory markers of hepatic fat accumulation.
Notably, semaglutide preferentially reduced fat mass and visceral adipose tissue (the dangerous belly fat surrounding organs) more than skeletal muscle or lean mass. Ultrasound-measured visceral fat thickness and a 12-point steatosis severity score both declined progressively from 3 months through the full 12-month treatment period.
Volpe, Sara; Lisco, Giuseppe; Fanelli, Margherita; Racaniello, Davide; Colaianni, Valentina; Triggiani, Domenico; Donghia, Rossella; Crudele, Lucilla; Rinaldi, Roberta; Sabbà, Carlo; Triggiani, Vincenzo; De Pergola, Giovanni; Piazzolla, Giuseppina · Prospective Cohort
RPEP-06572 · 2022Adeno-associated virus delivery of thymosin β4 (AAV-Tβ4) in mice with surgically induced heart attacks significantly reduced oxidative damage, inflammation, cardiac dysfunction, and fibrosis compared to controls.
At the cellular level, thymosin β4 counteracted hydrogen peroxide-induced damage in heart muscle cells by restoring mitophagy (the cleanup of damaged mitochondria) and reducing inflammasome activation. It also inhibited the growth of cardiac myofibroblasts — the cells responsible for producing scar tissue — and blocked TGF-β1-induced activation, a key driver of fibrosis. Thymosin β4 was naturally elevated in heart attack tissue, suggesting the body attempts to use this peptide as a protective response.
Wang, Fei; He, Yajuan; Yao, Naijuan; Ruan, Litao; Tian, Zhen ·