RPEP-06872 · 2023In a meta-analysis of five placebo-controlled trials, dulaglutide 1.5 mg reduced systolic blood pressure by −2.6 mmHg (95% CI: −3.8 to −1.5; p<0.001) compared to placebo. Mediation analysis revealed that 36% of this effect was weight-dependent (−0.9 mmHg) and 64% was weight-independent (−1.5 mmHg).
For pulse pressure, the total reduction was −2.5 mmHg, with 86% attributable to weight-independent mechanisms. Diastolic blood pressure showed minimal impact, with only a small weight-mediated effect. At the higher 4.5 mg dose, additional SBP and pulse pressure reductions beyond the 1.5 mg dose were primarily weight-mediated.
Ferdinand, Keith C; Dunn, Julia; Nicolay, Claudia; Sam, Flora; Blue, Emily K; Wang, Hui ·
RPEP-06875 · 2023Across 47 observational cohort studies, CGRP monoclonal antibodies showed strong real-world effectiveness for migraine prevention:
- 54% of patients (95% CI 49–59%) achieved at least 50% reduction in monthly migraine days
- Mean monthly migraine reduction: approximately 7.7 days (95% CI 7.0–8.4)
- 57% of patients (95% CI 48–64%) achieved at least 50% reduction in monthly headache days
- Mean monthly headache reduction: approximately 8.8 days (95% CI 7.5–10.1)
Subgroup analyses by specific drug (erenumab, fremanezumab, galcanezumab, eptinezumab) and migraine type showed consistent results.
Ferreira, Vinicius L; Mainka, Felipe F; Wiens, Astrid; Pontarolo, Roberto ·
RPEP-06876 · 2023Using a combination of sodium-23 NMR spectroscopy, molecular dynamics simulations, and mutagenesis experiments, researchers demonstrated that sodium ions bind to a conserved allosteric site on the ghrelin receptor (GHSR). This binding shifts the receptor's conformational equilibrium toward its inactive state, decreasing both basal (constitutive) activity and agonist-induced G protein activation.
The allosteric sodium site is conserved across class A GPCRs, but this study specifically characterized its functional impact on GHSR for the first time, establishing sodium as an integral component of the ghrelin signaling machinery.
Ferré, Guillaume; Gomes, Antoniel A S; Louet, Maxime; Damian, Marjorie; Bisch, Paulo M; Saurel, Olivier; Floquet, Nicolas; Milon, Alain; Banères, Jean-Louis ·
RPEP-06880 · 2023Clinical studies of dual GLP-1/GIP receptor agonists (unimolecular dual-receptor agonists or UDRAs) have demonstrated favorable results both as standalone treatments and in combination with other diabetes drugs. The additive insulin-boosting effects of dual GLP-1 and GIP receptor activation were expected based on what each hormone does individually.
However, the additional benefits from adding glucagon receptor (GCGR) activation in triple agonists were largely unexpected, since glucagon normally raises blood sugar. Whether simultaneous stimulation of these three receptor pathways creates synergistic or antagonistic interactions at the cellular level remains unknown and requires further investigation.
Folli, Franco; Finzi, Giovanna; Manfrini, Roberto; Galli, Alessandra; Casiraghi, Francesca; Centofanti, Lucia; Berra, Cesare; Fiorina, Paolo; Davalli, Alberto; La Rosa, Stefano; Perego, Carla; Higgins, Paul B ·
RPEP-06881 · 2023Peptide receptor radionuclide therapy (PRRT) using somatostatin analogs labeled with lutetium-177 or yttrium-90 is now an established, FDA- and EMA-approved treatment for neuroendocrine tumors (NETs). The same peptides labeled with gallium-68 ([68Ga]-DOTA-peptides) serve as diagnostic imaging agents — making this a true theranostic approach where one peptide family both finds and treats cancer.
The review highlights emerging advances: personalized treatment schemes, SSTR antagonists (which may outperform current agonists), alpha-emitting radioisotopes for therapy, 18F-labeled somatostatin analogs for improved imaging, and combination strategies pairing PRRT with other treatments.
Fortunati, Emilia; Bonazzi, Norma; Zanoni, Lucia; Fanti, Stefano; Ambrosini, Valentina · Review
RPEP-06884 · 2023At week 26, orforglipron at doses of 12 mg or greater produced statistically superior HbA1c reductions compared to placebo. The maximum HbA1c reduction was -2.10% (placebo-adjusted: -1.67%), compared to -0.43% with placebo and -1.10% with injectable dulaglutide 1.5 mg weekly.
Weight loss with orforglipron reached up to -10.1 kg (placebo-adjusted: -7.9 kg), compared to -2.2 kg with placebo and -3.9 kg with dulaglutide.
Gastrointestinal adverse events occurred in 44-70% of orforglipron-treated patients (vs. 18% placebo, 34% dulaglutide) but were mostly mild to moderate. Clinically significant hypoglycemia was rare (3 orforglipron patients, 1 dulaglutide). No severe hypoglycemia occurred. The study completion rate was 92%, with 79% completing the full 26 weeks of treatment.
Frias, Juan P; Hsia, Stanley; Eyde, Sarah; Liu, Rong; Ma, Xiaosu; Konig, Manige; Kazda, Christof; Mather, Kieren J; Haupt, Axel; Pratt, Edward; Robins, Deborah ·
RPEP-06887 · 2023This comprehensive review synthesizes the current understanding of defensins — a family of cationic antimicrobial peptides produced primarily by Paneth cells, neutrophils, and epithelial cells. The review covers their structural features, evolutionary history, and antimicrobial mechanisms, as well as their broader biological roles in immune homeostasis, chemotaxis, mucosal barrier maintenance, gut microbiota regulation, intestinal development, and regulation of cell death.
The authors detail the clinical relevance of defensins across multiple disease areas including infectious diseases, inflammatory bowel disease, diabetes and obesity, chronic inflammatory lung disease, periodontitis, and cancer. They also examine how nutrients — fatty acids, amino acids, microelements, plant extracts, and probiotics — regulate defensin expression, offering potential dietary strategies for modulating host defense.
Fu, Jie; Zong, Xin; Jin, Mingliang; Min, Junxia; Wang, Fudi; Wang, Yizhen · Review
RPEP-06891 · 2023All three tirzepatide doses were both non-inferior and superior to insulin glargine for HbA1c reduction at week 40:
- Tirzepatide 5mg: -2.24% (treatment difference vs. insulin: -1.29%)
- Tirzepatide 10mg: -2.44% (treatment difference: -1.49%)
- Tirzepatide 15mg: -2.49% (treatment difference: -1.54%)
- Insulin glargine: -0.95%
(All P<0.001)
HbA1c <7.0% targets achieved: tirzepatide 75.4-86.0% vs. insulin 23.7% (P<0.001). Body weight changes: tirzepatide -5.0 to -7.2 kg vs. insulin +1.5 kg (P<0.001). No severe hypoglycemia reported with tirzepatide.
Gao, Leili; Lee, Byung Wan; Chawla, Manoj; Kim, Joshua; Huo, Li; Du, Liying; Huang, Yan; Ji, Linong ·
RPEP-06892 · 2023The stapled peptide S-TBS, derived from the talin-binding segment of RIAM, exhibited stronger binding to talin than the unmodified peptide and inhibited the talin-integrin interaction. X-ray crystallography confirmed S-TBS binds to the talin rod through the same interface as the natural TBS sequence.
Critically, the helical stapled peptide demonstrated excellent cell permeability (a common challenge for peptide drugs) and effectively suppressed integrin activation in living cells in a talin-dependent manner. The 'double-hit' approach — targeting two distinct sites with a single peptide — represents a novel design strategy for multi-specific peptidomimetic inhibitors.
Gao, Tong; Cho, Eun-Ah; Zhang, Pingfeng; Wu, Jinhua ·
RPEP-06900 · 2023When presented with the clinical profiles of tirzepatide (5, 10, and 15mg) versus semaglutide 1mg based on head-to-head trial data, predicted preference for tirzepatide was 95.6% in the US and 86.3% in the UK.
The key drivers of preference differed between countries: US patients weighted HbA1c reduction most heavily (26.3% relative attribute importance), while UK patients prioritized avoiding hypoglycemia (32.8%). Both groups preferred greater HbA1c improvement, greater weight loss, lower nausea frequency, lower hypoglycemia risk, and the single-use pre-filled pen delivery system. Weight reduction and nausea frequency also significantly influenced preferences.
Gelhorn, Heather L; Osumili, Beatrice; Brown, Katelyn; Ross, Melissa M; Schulz, Andrea; Fernandez, Gabriela; Boye, Kristina S ·
RPEP-06901 · 2023Compared to placebo over 2 years, dulaglutide was associated with greater reductions or lesser rises in NT-proBNP, GDF-15, high-sensitivity CRP, and a greater rise in C-peptide. It also reduced 2-hydroxybutyric acid and increased threonine levels.
Critically, of these biomarkers, only NT-proBNP and GDF-15 were also independently associated with cardiovascular events (MACE). NT-proBNP: OR 1.267 (95% CI 1.119–1.435, p<0.001); GDF-15: OR 1.937 (95% CI 1.424–2.634, p<0.001). This dual association — reduced by dulaglutide AND predictive of heart events — suggests these markers may mediate the drug's cardiovascular protection.
Gerstein, Hertzel C; Lee, Shun-Fu; Paré, Guillaume; Bethel, M Angelyn; Colhoun, Helen M; Hoover, Anastasia; Lakshmanan, Mark; Lin, Yanzhu; Pirro, Valentina; Qian, Hui-Rong; Ruotolo, Giacomo; Ryden, Lars; Wilson, Jonathan M; Duffin, Kevin L ·
RPEP-06902 · 2023Microsecond-long multi-copy molecular dynamics simulations revealed that the apo (empty) SSTR2 receptor is more flexible than when bound to ligands. Extracellular loop 2 (ECL2) closes upon binding the agonist octreotide but not the antagonist CYN154806, providing a structural explanation for agonist vs. antagonist selectivity.
All peptide ligands (somatostatin, octreotide, and CYN154806) interact similarly with residues deep in the binding pocket. However, agonists and the antagonist show distinct interaction patterns with residues at the outer portion of the pocket near the extracellular loops, which is the key structural feature distinguishing receptor activation from blockade.
Gervasoni, Silvia; Guccione, Camilla; Fanti, Viviana; Bosin, Andrea; Cappellini, Giancarlo; Golosio, Bruno; Ruggerone, Paolo; Malloci, Giuliano ·
RPEP-06905 · 2023The co-assembly of fibrinogen with Fmoc-FF and Fmoc-RGD peptides produced a novel supramolecular fiber type with tunable morphology and mechanical properties. Key findings include:
- The composite hydrogels had significantly improved mechanical properties compared to pure fibrin gels
- Ex vivo testing confirmed excellent biocompatibility
- In vivo experiments showed no inflammatory response or tissue damage
- The gels were completely resorbed in a short time
- The three-component system co-assembles under physiological conditions triggered by thrombin, enabling injectable formulations
Gila-Vilchez, Cristina; Mañas-Torres, Mari Carmen; García-García, Óscar Darío; Escribano-Huesca, Alfredo; Rodríguez-Arco, Laura; Carriel, Víctor; Rodriguez, Ismael; Alaminos, Miguel; Lopez-Lopez, Modesto Torcuato; Álvarez de Cienfuegos, Luis ·
RPEP-06909 · 2023Using single-cell RNA sequencing, researchers identified a distinct gene expression profile in the rare cardiomyocytes that enter the cell cycle after myocardial infarction in mice. They found increased DNA synthesis (EdU incorporation) in cardiomyocytes 3 days post-infarction, confirmed by clonal expansion in the border zone of infarcted tissue using multi-color lineage tracing.
Among the enriched genes in proliferating cardiomyocytes, a combination of thymosin β4 (TMSB4) and prothymosin α (PTMA) proved most effective. When delivered therapeutically to the heart wall after ischemic injury, this two-peptide cocktail promoted cardiomyocyte proliferation and attenuated cardiac dysfunction. The study demonstrates that both activating cell division and creating a permissive microenvironment are necessary for cardiac regeneration.
Gladka, Monika M; Johansen, Anne Katrine Z; van Kampen, Sebastiaan J; Peters, Marijn M C; Molenaar, Bas; Versteeg, Danielle; Kooijman, Lieneke; Zentilin, Lorena; Giacca, Mauro; van Rooij, Eva ·
RPEP-06912 · 2023Peptide-conjugated antisense oligonucleotides (CPP-PMOs) targeting miR-23b and miR-218 significantly increased MBNL1 protein levels in myotonic dystrophy type 1 (DM1) cells. Some candidates achieved this at concentrations nearly two orders of magnitude below the median toxic concentration, with up to a 5.38-fold better therapeutic window compared to previous antagomiR approaches.
In HSALR mouse models, intravenous injections of CPP-PMOs improved molecular, histopathological, and functional disease phenotypes without signs of toxicity, demonstrating successful in vivo delivery to affected tissues.
González-Martínez, Irene; Cerro-Herreros, Estefanía; Moreno, Nerea; García-Rey, Andrea; Espinosa-Espinosa, Jorge; Carrascosa-Sàez, Marc; Piqueras-Losilla, Diego; Arzumanov, Andrey; Seoane-Miraz, David; Jad, Yahya; Raz, Richard; Wood, Matthew J; Varela, Miguel A; Llamusí, Beatriz; Artero, Rubén ·
RPEP-06918 · 2023This is a trial protocol paper, not a results paper. The key preclinical finding supporting the trial is that the H3K27M-vac peptide vaccine induced mutation-specific immune responses and suppressed growth of H3K27M-positive tumors in MHC-humanized rodent models.
The trial design calls for 15 adult patients with newly diagnosed H3K27M-mutant diffuse midline gliomas to receive the 27-amino-acid peptide vaccine alongside radiation therapy and the PD-L1-targeting antibody atezolizumab. Vaccines are administered bi-weekly during radiation, then every 6 weeks for a total of 11 doses.
Grassl, Niklas; Sahm, Katharina; Süße, Heike; Poschke, Isabel; Bunse, Lukas; Bunse, Theresa; Boschert, Tamara; Mildenberger, Iris; Rupp, Anne-Kathleen; Ewinger, Max Philipp; Lanz, Lisa-Marie; Denk, Monika; Tabatabai, Ghazaleh; Ronellenfitsch, Michael W; Herrlinger, Ulrich; Glas, Martin; Krex, Dietmar; Vajkoczy, Peter; Wick, Antje; Harting, Inga; Sahm, Felix; von Deimling, Andreas; Bendszus, Martin; Wick, Wolfgang; Platten, Michael ·
RPEP-06921 · 2023Researchers developed a combinatorial library of cell-penetrating peptides (CPPs) combined with lysosomal sorting signals and tested them for cell-type specificity in retinal cells versus corneal cells. Several CPP candidates showed up to 4-fold greater internalization in ARPE19 retinal pigment epithelium cells compared to B3 corneal lens cells, demonstrating that CPPs can be engineered for cell-type selectivity rather than the non-specific uptake typically seen.
Follow-up cargo transport studies confirmed that the selected CPPs could effectively deliver payload into ARPE19 cells and target it specifically to lysosomes — the cellular organelles where storage diseases cause dysfunction and eventual blindness.
Grohn, Kris; Parella, Kyle; Lumen, Ellie; Colegrove, Hanna; Bjork, Victor; Franceski, Alana; Wolfe, Aaron; Moody, Kelsey · In Vitro
RPEP-06922 · 2023Six novel peptides were identified from in silico proteolysis of buffalo milk proteins: two ACE inhibitors (KPW and RGP) and four DPP-IV inhibitors (RGP, KPW, FPK, and KFTW). Laboratory validation confirmed their activity:
ACE inhibition: KPW (IC50 = 136.28 ± 10.77 μM, competitive inhibitor) and RGP (IC50 = 104.72 ± 8.37 μM, competitive inhibitor).
DPP-IV inhibition: KPW (IC50 = 82.52 ± 10.37 μM, mixed-type inhibitor), FPK (IC50 = 126.57 ± 8.45 μM, mixed-type inhibitor), and KFTW (IC50 = 873.92 ± 32.89 μM, competitive inhibitor).
Notably, KPW inhibited both ACE and DPP-IV, making it a dual-activity peptide.
Gu, Yuxiang; Li, Xing; Qi, Xiaofen; Ma, Ying; Chan, Eric Chun Yong ·
RPEP-06923 · 2023NOP receptor expression was detected on peritoneal nerve fibers in both endometriosis patients and healthy controls, but expression was increased in endometriosis-associated nerve fibers. NOP frequently colocalized with substance P, CGRP, tyrosine hydroxylase, and VIP-positive nerve fibers, indicating it is expressed on both sensory (pain-transmitting) and autonomic nerve fibers.
This is the first study to characterize NOP receptor expression specifically in endometriosis-associated nerve fibers, establishing a molecular basis for testing NOP agonists as analgesics in this condition.
Guan, Qihui; Velho, Renata Voltolini; Jordan, Alice; Pommer, Sabrina; Radde, Irene; Sehouli, Jalid; Mechsner, Sylvia · Observational Human Tissue
RPEP-06924 · 2023In vascular dementia rats, dulaglutide treatment produced multiple neuroprotective effects:
- Cognitive improvement: Morris water maze testing showed significantly reduced cognitive decline
- Neuroprotection: Neuronal damage in the hippocampus was significantly alleviated
- Reduced gliosis: Microglial and astrocyte proliferation (inflammation markers) were decreased
- Anti-apoptotic effects: BCL2/BAX ratio and cleaved caspase-3 indicated reduced cell death
- Autophagy regulation: P62, LC3B, and Beclin-1 markers showed normalized autophagy
- Mechanism: PI3K/Akt/mTOR signaling pathway was activated, with the mTOR repressor Deptor downregulated
RNA sequencing confirmed that mTOR pathway genes were significantly enriched among differentially expressed genes in the dulaglutide group.
Guan, Tianyuan; Xiao, Yining; Xie, Xiaohua; Meng, Nan; Qi, Qianqian; Xu, Jing; Jiang, Xin; Zhang, Zhe; Teng, Zhenjie; Lv, Peiyuan ·
RPEP-06927 · 2023In 3,291 Chinese adults with T2DM prescribed dulaglutide in routine clinical practice (46 hospitals, 2020-2021):
- HbA1c: -1.65% from baseline at 24 weeks (p<0.001)
- Body weight: -2.62 kg from baseline at 24 weeks (p<0.001)
- TEAEs: Reported in 40.5% — nausea (5.9%), diarrhea (5.6%), decreased appetite (5.4%)
- Serious AEs: 4.9% of patients
- Treatment discontinuation due to AEs: 6.4%
Greater HbA1c reductions seen in patients with:
- T2DM duration ≤5 years (p=0.002)
- Baseline HbA1c ≥8.5% (p<0.001)
- No atherosclerotic cardiovascular disease (p=0.002)
Guo, Lixin; Li, Li; Yu, Qiurong; Wang, Na; Chen, Jun; Xi, Yue; Wang, Huan; Wang, Yihua; Xu, Jiawei ·
RPEP-06934 · 2023Coiled-coil molecular zippers with 3 and 4 repeating units (K/E zipper n=3 and n=4) formed stable 1:1 hybrid complexes between the autophagy-inducing peptide and the cell-penetrating peptide. Both successfully delivered the functional peptide into cells.
Interestingly, the 3-repeat zipper induced autophagy more intensively than the 4-repeat version, suggesting that the optimal biological activity depends on a balance between how strongly the zipper holds together and how readily it releases the functional peptide inside the cell. Shorter zippers (n=1 and n=2) did not form stable hybrids. None of the peptides or zippers showed significant cytotoxicity.
Hakata, Yoshiyuki; Yamashita, Kazuma; Hashimoto, Sonoko; Ohtsuki, Takashi; Miyazawa, Masaaki; Kitamatsu, Mizuki ·
RPEP-06939 · 2023Using isogenic AMP gene deletions in Drosophila, no individual antimicrobial peptide had a major effect on lifespan, with the possible exception of Defensin. However, ΔAMP14 flies lacking seven AMP gene families showed significantly reduced lifespan.
The lifespan reduction was traced to microbiome dysbiosis: aged ΔAMP14 flies had increased bacterial loads in their food. Critically, raising ΔAMP14 flies under germ-free conditions restored their lifespan, proving the reduced lifespan was due to loss of microbial control, not a direct role of AMPs in aging or inflammation.
Hanson, Mark A; Lemaitre, Bruno ·
RPEP-06941 · 2023Among 304 veterans converted from liraglutide (0.6 or 1.2 mg daily) to semaglutide (0.25 mg weekly, titrated to 0.5 mg weekly):
- Mean HbA1c decreased significantly from 8.1% (SD 1.5) to 7.6% (SD 1.4) at 3–12 months (P significant)
- Mean baseline blood glucose: 187.4 mg/dL (SD 44.2)
- Mean baseline body weight: 112.9 kg (SD 23.0); significant weight loss observed (P < 0.001)
- Minimal changes to antihyperglycemic regimens were needed
- Cost savings exceeded $400,000 from the conversion
- Common adverse effects: hypoglycemia and gastrointestinal intolerance
Hardin, Maiah; Adanse, Fiona; Schexnayder, Chandler; Malveaux, Janeca; Agbahiwe, Sylvester ·
RPEP-06946 · 2023The iRGD-PROTAC conjugate (iPR) was created by linking the tumor-penetrating cyclic peptide iRGD (CRGDK/RGPD/EC) to a BRD4-targeting PROTAC through a glutathione (GSH)-responsive linker that releases the active drug inside tumor cells.
Compared to the unconjugated PROTAC, the iRGD-PROTAC conjugate showed enhanced water solubility, improved tumor-targeting capability, and deeper penetration within breast cancer tissues. These improvements translated to increased anti-breast cancer efficacy in both animal models and patient-derived organoids, validating the concept that peptide-guided delivery can overcome key limitations of PROTAC-based cancer therapies.
He, Shipeng; Fang, Yuxin; Wu, Minghao; Zhang, Peifeng; Gao, Fei; Hu, Honggang; Sheng, Chunquan; Dong, Guoqiang ·
RPEP-06949 · 2023Tirzepatide 15 mg produced significantly greater body weight and fat mass reductions compared to both semaglutide 1 mg and placebo over 28 weeks in type 2 diabetes patients. Both tirzepatide and semaglutide significantly reduced appetite versus placebo, but appetite scores and energy intake reductions during ad libitum lunch did not differ between the two drugs.
This surprising finding — that tirzepatide and semaglutide suppress appetite equally but tirzepatide produces more weight loss — suggests tirzepatide's superior weight loss involves mechanisms beyond appetite reduction, possibly including effects on 24-hour energy intake, substrate utilization, or energy expenditure.
Heise, Tim; DeVries, J Hans; Urva, Shweta; Li, Jing; Pratt, Edward J; Thomas, Melissa K; Mather, Kieren J; Karanikas, Chrisanthi A; Dunn, Julia; Haupt, Axel; Milicevic, Zvonko; Coskun, Tamer ·
RPEP-06951 · 2023From transcripts obtained from the skin and oral mucosa of Crotalus aquilus, researchers identified the first cathelicidin-like peptide from this species. The peptide precursor contained a signal peptide, a 101-amino-acid conserved cathelin domain, an anionic region, and a 34-amino-acid mature peptide (Aquiluscidin/Aq-CATH).
Both Aq-CATH and its shorter 23-amino-acid derivative Vcn-23 demonstrated potent broad-spectrum antibacterial activity with MIC values of 2-8 µg/mL against all tested Gram-positive and Gram-negative bacteria. At concentrations up to 50 µM, neither peptide showed significant hemolytic activity. However, cytotoxicity testing showed cell viability dropped below 65% at 25 µM, indicating a window between antimicrobial and cytotoxic concentrations that needs optimization.
Hernández-Arvizu, Edwin Esaú; Silis-Moreno, Teresa Monserrat; García-Arredondo, José Alejandro; Rodríguez-Torres, Angelina; Cervantes-Chávez, José Antonio; Mosqueda, Juan ·
RPEP-06954 · 2023In the first-ever viral resistance analysis of bulevirtide (a lipopeptide entry inhibitor for hepatitis delta virus), no drug resistance was detected in any patient through 24 weeks of treatment. Deep sequencing of the drug's target regions found no amino acid changes associated with reduced sensitivity to bulevirtide — not in the 20 non-responders, not in the 1 patient with virologic breakthrough, and not in any baseline samples.
Phenotypic testing of 116 baseline samples showed similar bulevirtide susceptibility (EC50 values) across responders, partial responders, and non-responders regardless of any HBV or HDV genetic variations present. This demonstrates that bulevirtide has a high barrier to resistance, and that non-response to treatment is caused by other unknown mechanisms — not viral escape from the drug.
Hollnberger, Julius; Liu, Yang; Xu, Simin; Chang, Silvia; Martin, Ross; Manhas, Savrina; Aeschbacher, Thomas; Han, Bin; Yazdi, Tahmineh; May, Lindsey; Han, Dong; Shornikov, Alex; Flaherty, John; Manuilov, Dmitry; Suri, Vithika; Asselah, Tarik; Lampertico, Pietro; Wedemeyer, Heiner; Aleman, Soo; Richards, Christopher; Mateo, Roberto; Maiorova, Evguenia; Cihlar, Tomas; Mo, Hongmei; Urban, Stephan · Clinical Trial
RPEP-06956 · 2023In a meta-analysis of four studies (16 subgroups) from head-to-head RCTs, abaloparatide showed significantly greater BMD improvements than teriparatide at the femoral neck (WMD = 1.58, 95% CI 0.52–2.63) and total hip (WMD = 1.46, 95% CI 0.59–2.32) — both rated high-quality evidence by GRADE criteria.
All BMD parameters at 24 weeks favored abaloparatide except lumbar spine. The incidence of hypercalcemia was 51% lower with abaloparatide compared to teriparatide. No significant differences were found in serious adverse events or deaths between the two drugs. However, compared to placebo, abaloparatide was associated with higher risks of nausea and palpitations. Fracture data was insufficient for meaningful analysis.
Hong, Pan; Liu, Ruikang; Rai, Saroj; Liu, JiaJia; Zhou, YeMing; Zheng, Yu; Li, Jin ·
RPEP-06960 · 2023Two permeation enhancers — sodium caprate and SNAC (the technology behind oral semaglutide) — have opposite effects on different types of peptide drugs depending on the peptide's water solubility. In the presence of intestinal bile salts, both enhancers promoted the release of hydrophobic (fat-loving) peptides but inhibited the release of water-soluble peptides from molecular aggregates.
SNAC caused insulin to form more beta-sheet structures, while sodium caprate preserved insulin's alpha-helical and random coil structures. These structural changes matter because they affect whether the peptide drug is active or aggregated when it reaches the intestinal wall. The findings suggest that permeation enhancer selection must be matched to each specific peptide's physical properties.
Hossain, Shakhawath; Kneiszl, Rosita; Larsson, Per · Computational
RPEP-06961 · 2023A peptide-drug conjugate called HR97-SunitiGel, delivered as an eye drop in rats, provided up to two weeks of retinal ganglion cell protection after the last dose. This effectively doubled the therapeutic window compared to the drug formulation without the engineered peptide.
The system combined two technologies: a hypotonic gel-forming eye drop and a melanin-binding, cell-penetrating peptide. The peptide component extended how long the drug remained inside the eye, allowing once-daily dosing to achieve sustained therapeutic concentrations of sunitinib in the back of the eye.
Hsueh, Henry T; Chou, Renee Ti; Rai, Usha; Kolodziejski, Patricia; Liyanage, Wathsala; Pejavar, Jahnavi; Mozzer, Ann; Davison, Charlotte; Appell, Matthew B; Kim, Yoo Chun; Leo, Kirby T; Kwon, HyeYoung; Sista, Maanasa; Anders, Nicole M; Hemingway, Avelina; Rompicharla, Sri Vishnu Kiran; Pitha, Ian; Zack, Donald J; Hanes, Justin; Cummings, Michael P; Ensign, Laura M · Animal Study
RPEP-06968 · 2023Patients receiving dulaglutide plus insulin degludec had significantly lower glucose variability across all measures (SDBG, MAGE, LAGE, and PPGE) compared to insulin degludec alone (all p<0.05). The combination group achieved time-in-range (TIR) targets much faster: by day 10, 100% had TIR ≥70% compared to only 67% in the control group.
Appetite decreased significantly at 1 week after starting dulaglutide but began to return by 3 months. At 6 months, 89.2% of patients in the combination group were still on dulaglutide, indicating strong persistence. TIR was significantly associated with preserved islet (beta cell) function.
Huang, Jinxin; Hua, Fei; Jiang, Xiaohong; Zhang, Xingguang; Yang, Minxing; Wang, Long; Huang, Xiaolin; Luo, Kaiming ·
RPEP-06969 · 2023Using an integrated peptidomics screening approach, researchers identified 31 ACE substrates from 478 peptides found in milk hydrolysate. The study revealed specific rules governing which peptides ACE can cleave: the most common residue at the P1' cleavage position was leucine or serine, while ACE would not cleave peptides when P1' is proline, P2' is aspartate/glutamate, or P1 is isoleucine.
Two peptides — AYFYPELFR and HLPLPLLQSW — were identified as substrate-type ACE inhibitors that significantly slowed the breakdown of angiotensin I, the natural ACE substrate involved in blood pressure regulation. These milk-derived peptides could serve as natural ACE inhibitors.
Huang, Ju-Hsuan; Nong, Nhung Thi Phuong; Hsu, Jue-Liang · In Vitro
RPEP-06971 · 2023Rehmannia alcohol extract and its active component Rehmannioside D delayed cartilage degradation and reduced inflammation in osteoarthritis rats. The extract significantly reduced secretion of calcitonin gene-related peptide (CGRP) and substance P (SP) — two neuropeptides central to pain signaling. Functional MRI revealed that the treatment reversed pathological changes in the cerebral cortex and hippocampus, indicating the extract influences brain pain processing regions in addition to its local anti-inflammatory effects at the joint.
Huang, Yanfeng; Lin, Qing; Tan, Xue; Jia, Liangliang; Li, Hui; Zhu, Zaishi; Fu, Changlong; Wang, Lili; Liu, Linlong; Mao, Min; Yi, Zhouping; Ma, Dezun; Li, Xihai ·
RPEP-06975 · 2023Among 624 new users of anti-CGRP mAbs (erenumab n=295, galcanezumab n=223, fremanezumab n=106), treatment persistence declined progressively: 69% at 6 months, 48% at 12 months, and only 6% at 15 months. Treatment switching between antibodies occurred in about 6% of patients at 15 months.
For patients with regular triptan use at baseline, mean monthly triptan consumption decreased by 4.4 dosage units at 3 months, 5.2 at 6 months, 5.5 at 9 months, 5.4 at 12 months, and 4.5 at 15 months. The patient population was predominantly female (78%) with a mean age of 49.2 years.
Hyeraci, Giulia; Paoletti, Olga; Iannone, Luigi Francesco; Gini, Rosa; De Cesaris, Francesco; Geppetti, Pierangelo; Roberto, Giuseppe ·
RPEP-06982 · 2023Researchers isolated a specific five-amino-acid peptide (Asp-Asn-Arg-Tyr-Tyr, molecular weight 730.31 Da) from enzymatic digestion of velvet antler that powerfully inhibits angiotensin I-converting enzyme (ACE), a key enzyme in blood pressure regulation. The peptide showed an IC50 value of 3.72 μM against ACE — indicating potent inhibitory activity at very low concentrations. Molecular docking analysis confirmed stable binding between the peptide and ACE at multiple active-site residues. When given orally to spontaneously hypertensive rats, the peptide significantly reduced blood pressure.
Im, Seung Tae; Lee, Seung-Hong · In Vitro + Animal Study
RPEP-06988 · 2023In situ mixing of RADA16 self-assembling peptide with poly(ethylene glycol) produced double-network hydrogels through sequential network formation: first RADA16 self-assembly, then PEG chemical cross-linking. The resulting hydrogels exhibited up to a 10-fold increase in fracture energy compared to single-network controls, demonstrating dramatically improved mechanical toughness.
Cells seeded on the DN hydrogel surfaces showed good attachment, confirming the cell-adhesive properties of the RADA16 peptide component were preserved. The entire process used only synthetic, biocompatible materials and avoided free-radical polymerization — a key advantage for biological applications.
Ishikawa, Shohei; Sakai, Takamasa ·
RPEP-07003 · 2023Novel stapled/stitched peptides were designed to target the N-terminal helical bundle of the DAXX oncoprotein, binding with higher affinity than DAXX's known natural interaction partners (Rassf1C, p53, Mdm2, ATRX). The peptides effectively inhibited DAXX and released its auto-inhibited SUMO interaction motif, enabling it to bind SUMO-1. Critically, the stitched peptides entered cells and maintained nanomolar intracellular concentrations for at least 24 hours without disrupting cell membranes.
Jelinska, Clare; Kannan, Srinivasaraghavan; Frosi, Yuri; Ramlan, Siti Radhiah; Winnerdy, Fernaldo; Lakshminarayanan, Rajamani; Johannes, Charles W; Brown, Christopher J; Phan, Anh-Tuan; Rhodes, Daniela; Verma, Chandra S ·
RPEP-07005 · 2023The review identifies the current approved anti-obesity medications and their successors:
**Currently approved (long-term):** Orlistat, naltrexone/bupropion, phentermine/topiramate, liraglutide (GLP-1 RA), semaglutide (GLP-1 RA)
**Awaiting approval:** Tirzepatide (dual GLP-1/GIP agonist)
**In Phase 3 trials:** Semaglutide/cagrilintide combination (GLP-1 + amylin analog), oral semaglutide for obesity, orforglipron (oral non-peptide GLP-1 agonist), BI 456906, retartrutide (triple GLP-1/GIP/glucagon agonist)
The Korean KSSO guidelines recommend pharmacotherapy for adults with BMI ≥25 kg/m² who haven't responded to non-pharmacological treatments, emphasizing personalized drug selection based on individual patient characteristics.
Jeon, Eonju; Lee, Ki Young; Kim, Kyoung-Kon ·
RPEP-07008 · 2023In a 14-week randomized, placebo-controlled trial, 50 healthy men who took 5g of specific collagen peptides daily alongside resistance training showed significantly greater improvements in patellar tendon structural properties compared to placebo. The study also assessed tendon stiffness, maximal voluntary knee extension strength, and rectus femoris muscle cross-sectional area. The collagen peptide supplementation led to significantly greater patellar tendon morphological adaptations beyond what resistance training alone achieved.
Jerger, Simon; Centner, Christoph; Lauber, Benedikt; Seynnes, Olivier; Friedrich, Till; Lolli, David; Gollhofer, Albert; König, Daniel ·
RPEP-07010 · 2023Researchers developed a novel peptide called Pen-X-ACIP that stabilizes the AMPK enzyme complex in fat tissue — a process that breaks down during cancer cachexia. When injected into tumor-bearing mice, the peptide prevented cachexia progression, preserved body weight and fat tissue mass, and did not affect tumor growth or cause side effects in other organs. The peptide was efficiently taken up by fat cells, inhibited the excessive fat breakdown (lipolysis) that drives wasting, and restored AMPK signaling. It also worked in human fat cells in the lab, providing a proof of concept for a first-in-class therapy.
Ji, Honglei; Englmaier, Felix; Morigny, Pauline; Giroud, Maude; Gräsle, Pamina; Brings, Sebastian; Szendrödi, Julia; Berriel Diaz, Mauricio; Plettenburg, Oliver; Herzig, Stephan; Rohm, Maria · Animal
RPEP-07013 · 2023The researchers engineered a self-cyclising 'autocyclase' protein that performs a unimolecular (single-molecule) head-to-tail macrocyclisation reaction. This approach is fundamentally different from existing enzyme-catalysed methods because it is a controllable self-reaction rather than requiring a separate enzyme to act on the substrate. The autocyclase produced cyclic peptides and proteins in high yield, and the unimolecular reaction mechanism addresses existing challenges in enzymatic cyclisation, such as substrate competition and concentration-dependent efficiency.
Jia, Xinying; Chin, Yanni K-Y; Zhang, Alan H; Crawford, Theo; Zhu, Yifei; Fletcher, Nicholas L; Zhou, Zihan; Hamilton, Brett R; Stroet, Martin; Thurecht, Kristofer J; Mobli, Mehdi ·
RPEP-07018 · 2023The antibody-drug conjugate (ADC) was created by fusing an antimicrobial peptide to the C-terminal end of the monoclonal antibody VSX, which targets P. aeruginosa lipopolysaccharide core. The ADC rapidly killed Pseudomonas strains, showed minimal toxicity to mammalian cells, and protected mice from P. aeruginosa lung infection when administered therapeutically. Additionally, the ADC was synergistic with several classes of conventional antibiotics, suggesting it could enhance existing treatments rather than replace them.
Johnson, Kenneth; Delaney, James C; Guillard, Thomas; Reffuveille, Fany; Varin-Simon, Jennifer; Li, Kai; Wollacott, Andrew; Frapy, Eric; Mong, Surin; Tissire, Hamid; Viswanathan, Karthik; Touti, Faycal; Babcock, Gregory J; Shriver, Zachary; Pentelute, Bradley L; Plante, Obadiah; Skurnik, David ·
RPEP-07024 · 2023Across 13 randomized controlled trials with 35,563 participants:
- Dulaglutide, exenatide, and semaglutide all outperformed placebo for cardiovascular outcomes in T2DM patients with coronary artery disease
- Significant reduction in non-fatal stroke incidence (p<0.00)
- Significant reductions compared to conventional treatment in:
- HbA1c (p<0.00)
- Fasting blood glucose (p<0.00)
- Body weight (p<0.00)
- Systolic blood pressure (p<0.00)
- Total cholesterol (p<0.00)
- LDL cholesterol (p<0.00)
Network pharmacology analysis identified the renin-angiotensin system as a key pathway, with matrix metalloproteinase 2 (MMP2) and renin as potential key targets. Each GLP-1 RA had distinct molecular target profiles (dulaglutide: 4 targets, exenatide: 5, semaglutide: 2).
Kan, Mengfan; Fu, Hui; Xu, Yunsheng; Yue, Zhaodi; Du, Bingyu; Chen, Qiang; Wang, Xueyin; Yu, Shaohong; Zhang, Zhongwen ·
RPEP-07025 · 2023MR-356, a synthetic GHRH agonist, reversed multiple hallmarks of HFpEF in the cardiometabolic mouse model:
- Reduced cardiac hypertrophy (heart thickening) and fibrosis (scarring)
- Reversed capillary rarefaction (loss of small blood vessels)
- Reduced pulmonary congestion
- Improved diastolic function — end-diastolic pressure and the end-diastolic pressure-volume relationship were reset to control levels
- Improved global longitudinal strain (GLS) and exercise capacity
- Normalized elevated pro-BNP, iNOS, and VEGF-A expression, indicating reduced myocardial stress and metabolic inflammation
Kanashiro-Takeuchi, Rosemeire M; Takeuchi, Lauro M; Dulce, Raul A; Kazmierczak, Katarzyna; Balkan, Wayne; Cai, Renzhi; Sha, Wei; Schally, Andrew V; Hare, Joshua M ·
RPEP-07027 · 2023Substance P alone significantly stimulated fibroblast proliferation and migration in both scratch assays (horizontal) and transwell assays (vertical) over 24 hours. Blocking the NK-1 receptor with spantide II abolished substance P's ability to stimulate cell migration. NK-2 receptor antagonism also significantly reduced migration but was less effective than NK-1 blockade. Combined NK-1 and NK-2 antagonism produced the greatest inhibition. TGF-β1 levels were significantly elevated in substance P-treated cell supernatants, while all receptor antagonist combinations showed significantly lower TGF-β1 levels than substance P alone.
Kant, Vinay; Mahapatra, Puspendra S; Gupta, Vijayta; Bag, Sadhan; Gopalakrishnan, Anu; Kumar, Dhirendra; Kumar, Dinesh ·
RPEP-07030 · 2023This meta-analysis of seven randomized controlled trials (1,037 patients total) found that the oral GLP-1 receptor agonists orforglipron and danuglipron significantly reduced HbA1c by 1.03% in people with type 2 diabetes compared to placebo. Weight loss was also significant: an average of 3.26 kg in diabetes patients and 7.52 kg in people with obesity.
Importantly, the drugs did not increase the risk of severe hypoglycemia or serious adverse events. However, gastrointestinal side effects were about 2.6 times more likely, and patients were about 2.9 times more likely to stop treatment due to adverse events.
Karakasis, Paschalis; Patoulias, Dimitrios; Pamporis, Konstantinos; Stachteas, Panagiotis; Bougioukas, Konstantinos I; Klisic, Aleksandra; Fragakis, Nikolaos; Rizzo, Manfredi ·
RPEP-07036 · 2023A 37-year-old male with type 2 diabetes who had been taking dulaglutide 0.75 mg weekly for approximately two years developed acute pancreatitis two weeks after his dose was increased to 1.5 mg weekly. Lipase was markedly elevated at 1,508 (normal is typically <60), and CT abdomen showed peripancreatic fat stranding consistent with acute pancreatitis. Symptoms included epigastric pain radiating to the back, nausea, and vomiting — developing after his last dose of Trulicity at the higher dosage.
Khan, Abu Baker; Shah, Aimal; Ahmad, Saad; Khan, Moiz I; Amir, Ahsan ·
RPEP-07037 · 2023The screened inhibitory peptides suppressed fibril formation in mutant huntingtin (mHtt) protein fragments, including both Htt(Q46) and Htt(Q103) — forms with 46 and 103 CAG repeats respectively. The Thioflavin T (ThT) fluorescence assay confirmed reduced fibril kinetics, and atomic force microscopy (AFM) imaging showed that the peptides prevented the characteristic fibril structures from assembling.
Khan, Anooshay; Özçelik, Cemile Elif; Begli, Ozge; Oguz, Oguzhan; Kesici, Mehmet Seçkin; Kasırga, Talip Serkan; Özçubukcu, Salih; Yuca, Esra; Seker, Urartu Ozgur Safak ·
RPEP-07039 · 2023A 41-year-old female underwent thyroidectomy for suspected medullary thyroid cancer, but pathology revealed a neuroendocrine tumor (NET) of unknown primary origin metastatic to the thyroid.
68Ga-DOTATATE PET/CT identified somatostatin receptor-expressing lesions in: liver, right cervical nodes, thoracic paravertebral soft tissue, precoccygeal soft tissue, and right acetabulum (bone).
Disease progressed on octreotide injections. The patient received 4 cycles of 177Lu-DOTATATE (Lutathera) PRRT over 8 months with:
- No side effects or toxicities reported
- Partial treatment response on early post-treatment scan at 6 weeks
Key diagnostic lesson: somatostatin receptor PET imaging both identifies the full extent of neuroendocrine disease and predicts response to PRRT, regardless of the organ of origin.
Khessib, Tasnim; Khessib, Samy; Berry, Gerald; Aparici, Mari ·