RPEP-04499 · 2019A recombinant oncolytic vaccinia virus engineered to express human β-defensin 2 (HBD2) — an antimicrobial peptide of the innate immune system — significantly inhibited tumor growth and metastasis in a mouse melanoma model. The HBD2-expressing virus recruited plasmacytoid dendritic cells to the tumor site, which then activated both CD4+ and CD8+ tumor-infiltrating T cells. This triggered both innate and adaptive immune responses against the cancer.
Sun, Ting; Luo, Yanxi; Wang, Minglong; Xie, Tian; Yan, Hui ·
RPEP-04508 · 2019Exenatide, acting through the GLP-1 receptor on human fibroblast-like synoviocytes (FLS), demonstrated multiple anti-inflammatory and protective effects in RA joint cells stimulated with TNF-α. Specifically, exenatide:
- Increased mitochondrial membrane potential, reversing TNF-α-induced mitochondrial dysfunction
- Reduced reactive oxygen species (ROS) production and NADPH oxidase 4 expression
- Decreased expression of tissue-degrading enzymes MMP-3 and MMP-13
- Lowered release of proinflammatory cytokines IL-1β, IL-6, MCP-1, and HMGB1
- Inhibited the p38/IκBα/NF-κB signaling pathway, a key inflammatory cascade
Tao, Yunxia; Ge, Gaoran; Wang, Qing; Wang, Wei; Zhang, Wenhao; Bai, Jiaxiang; Lin, Jiayi; Shen, Jining; Guo, Xiaobin; Xu, Yaozeng; Geng, Dechun ·
RPEP-04510 · 2019A series of novel KTTKS analogues — modified versions of the collagen-derived pentapeptide used in Matrixyl® skincare — were synthesized and tested for protease inhibition, cytotoxicity, and collagen stimulation in fibroblast cultures.
The palmitoyl-modified peptides were the most potent plasmin inhibitors, regardless of whether they were in acid or amide form. Swapping lysine for arginine in the sequences had no measurable biological effect. None of the synthesized analogues were cytotoxic to fibroblasts, and three of them promoted fibroblast cell growth. However, those three growth-promoting peptides did not show a clear concentration-dependent relationship in collagen or DNA biosynthesis assays.
Tałałaj, Urszula; Uścinowicz, Paulina; Bruzgo, Irena; Surażyński, Arkadiusz; Zaręba, Ilona; Markowska, Agnieszka · In Vitro
RPEP-04512 · 2019Previous work by this group found that fibromyalgia patients had significantly increased serum levels of substance P, hemokinin-1 (HK-1), IL-6, and TNF compared to sedentary controls.
Based on these findings, the authors propose a mechanistic hypothesis: mast cells in the thalamus release neuro-sensitizing molecules — including histamine, IL-1β, IL-6, TNF, CGRP, HK-1, and substance P — that activate thalamic pain-processing neurons either directly or via microglial stimulation. This creates a neuroinflammatory cycle that could explain the chronic, widespread pain of fibromyalgia. They suggest that inhibiting mast cell activation could be a novel therapeutic approach.
Theoharides, Theoharis C; Tsilioni, Irene; Bawazeer, Mona ·
RPEP-04514 · 2019MK0677, a potent ghrelin mimetic that activates the growth hormone secretagogue receptor (GHSR1α), improved hippocampal neurogenesis in 5xFAD Alzheimer's model mice when given at the asymptomatic stage. However, it failed to prevent amyloid-β deposition, synaptic loss, microglial activation, or cognitive impairment. At a dose of 3 mg/kg, MK0677 significantly increased mortality in these mice. Despite promoting new neuron formation, ghrelin receptor activation alone was insufficient to protect against Alzheimer's pathology.
Tian, Jing; Wang, Tienju; Wang, Qi; Guo, Lan; Du, Heng ·
RPEP-04517 · 2019Researchers developed an immuno-polymerase chain reaction (I-PCR) assay capable of detecting CJC-1295 — a growth hormone-releasing peptide — in horse blood at concentrations as low as 0.8 pg/mL. CJC-1295 is uniquely difficult to detect because it contains a reactive chemical group that covalently bonds to blood proteins, turning the peptide into a macromolecule that standard mass spectrometry screening cannot identify.
Using monoclonal antibodies specific to CJC-1295, the assay was validated in thoroughbred racehorses after administration of the drug. A screening threshold of 50 pg/mL was established to distinguish CJC-1295 from naturally occurring equine GHRH. The method confirmed detection of the peptide-protein conjugate in real-world samples.
Timms, Mark; Ganio, Katherine; Forbes, Grace; Bailey, Simon; Steel, Rohan · Experimental
RPEP-04518 · 2019The high-protein/moderate-carbohydrate (HP/MCHO) diet reduced hunger perception by 56.6% compared to the moderate-protein/high-carbohydrate (MP/HCHO) diet (p<0.05), measured approximately 34 months after initial weight loss.
The decreased hunger on the HP/MCHO diet was significantly associated with increased 2-AG (endocannabinoid) concentrations (p<0.05) and increased PYY (satiety peptide) concentrations (p<0.01). However, ad libitum food intake, insulin resistance (HOMA-IR), and incremental areas under the curve for GLP-1 and PYY were not significantly different between the two diet conditions.
Tischmann, Lea; Drummen, Mathijs; Gatta-Cherifi, Blandine; Raben, Anne; Fogelholm, Mikael; Hartmann, Bolette; Holst, Jens J; Matias, Isabelle; Cota, Daniela; Mensink, Ronald P; Joris, Peter J; Westerterp-Plantenga, Margriet S; Adam, Tanja C ·
RPEP-04522 · 2019CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, and eptinezumab) — the first migraine-specific preventive treatments — improve quality of life, reduce disability, and boost workplace productivity in migraine patients. Clinical trial data using patient-reported outcomes consistently showed improvements beyond just reducing headache days.
All four CGRP-mAbs achieved their primary endpoints of reducing monthly headache days and demonstrated meaningful impacts on daily functioning, global impression of change, and the overall burden of migraine on patients' lives.
Torres-Ferrus, Marta; Alpuente, Alicia; Pozo-Rosich, Patricia · Review
RPEP-04523 · 2019Both Lebetin 2 (L2) and BNP reduced infarct size, fibrosis, and inflammatory response after ischemia-reperfusion injury, with decreased leukocyte and proinflammatory M1 macrophage infiltration in the damaged area compared to untreated animals.
Critically, only L2 increased anti-inflammatory M2-like macrophages in the injured tissue — a key distinction from BNP. L2 also uniquely promoted higher densities of endothelial cells and cardiomyocytes, suggesting enhanced tissue repair and blood vessel preservation. A single injection provided both acute and prolonged cardioprotective effects, mediated at least partly through modulation of the post-ischemic inflammatory response.
Tourki, Bochra; Dumesnil, Anais; Belaidi, Elise; Ghrir, Slim; Godin-Ribuot, Diane; Marrakchi, Naziha; Richard, Vincent; Mulder, Paul; Messadi, Erij ·
RPEP-04528 · 2019The cocktail vaccine combining WT1 HLA class I and class II peptides was safe across all tested doses in patients with recurrent malignant glioma. No grade III/IV toxicity or dose-limiting toxicity was observed at any of the three dose levels of the class II peptide (0.75, 1.5, or 3 mg).
Among the 14 enrolled patients, 11 completed the initial 6-week vaccination course. Six of the 14 patients (43%) achieved stable disease at 6 weeks. The median overall survival was 24.7 weeks, with a 1-year survival rate of 36%.
Tsuboi, Akihiro; Hashimoto, Naoya; Fujiki, Fumihiro; Morimoto, Soyoko; Kagawa, Naoki; Nakajima, Hiroko; Hosen, Naoki; Nishida, Sumiyuki; Nakata, Jun; Morita, Satoshi; Sakamoto, Junichi; Oji, Yusuke; Oka, Yoshihiro; Sugiyama, Haruo ·
RPEP-04532 · 2019GHRH antagonist peptides protected lung endothelial barrier integrity by suppressing activation of MLC2, ERK1/2, and JAK2/STAT3 pathways while increasing P53 and pAMPK levels. In contrast, GHRH itself and the GHRH agonist MR409 disrupted endothelial barrier function through opposite effects on these pathways. Transendothelial resistance measurements confirmed that GHRH antagonists strengthened the barrier while GHRH and its agonists weakened it.
Uddin, Mohammad A; Akhter, Mohammad S; Singh, Sitanshu S; Kubra, Khadeja-Tul; Schally, Andrew V; Jois, Seetharama; Barabutis, Nektarios ·
RPEP-04533 · 2019Of two cell-penetrating peptides tested for delivering antisense oligonucleotides (ASOs) to myotonic dystrophy muscle cells, only PepFect14 (PF14) successfully delivered ASOs to the nucleus and corrected disease-typical abnormal splicing in a dose-dependent manner. Nona-arginine facilitated cellular uptake but failed to deliver ASOs to the nucleus. PF14 also protected ASOs from degradation. Nuclear ASO concentrations in the upper nanomolar range were required to dissolve MBNL1 protein foci — a hallmark of myotonic dystrophy type 1 (DM1).
van der Bent, M Leontien; Paulino da Silva Filho, Omar; Willemse, Marieke; Hällbrink, Mattias; Wansink, Derick G; Brock, Roland ·
RPEP-04537 · 2019In stapled peptides targeting the p53-MDM2/MDMX interaction:
- Replacing L-cysteine residues with 'cysteine analogues' of different stereochemistry (D vs. L), side chain length, and beta-carbon substitution produced significant changes in binding affinity and target selectivity
- Some modifications, particularly incorporating two D-cysteine residues, favorably altered the positions of key functional amino acid side chains
- Computationally constructed homology models correlated with experimental surface plasmon resonance (SPR) binding data
- The approach demonstrates that the thiol-containing residue in cysteine-stapled peptides is not just a structural linker but actively influences target binding
This provides a new dimension for optimizing stapled peptide drug candidates beyond the staple chemistry itself.
Verhoork, Sanne J M; Jennings, Claire E; Rozatian, Neshat; Reeks, Judith; Meng, Jieman; Corlett, Emily K; Bunglawala, Fazila; Noble, Martin E M; Leach, Andrew G; Coxon, Christopher R ·
RPEP-04538 · 2019Central (intracerebroventricular) ghrelin infusion increased aggression in male mice using the resident-intruder test, while systemic ghrelin injection did not — indicating the effect requires direct brain action. Blocking the ghrelin receptor (GHSR-1A) with JMV2959 reduced aggression, and this anti-aggressive effect was abolished when brain serotonin was depleted. Ex vivo biochemical data pointed to serotonin in the amygdala as the key mediator. In a human genetic study of 784 young men, the Leu72Leu genotype of the pre-pro-ghrelin gene was associated with greater aggression specifically in those with hazardous alcohol use.
Vestlund, Jesper; Winsa-Jörnulf, Julia; Hovey, Daniel; Lundström, Sebastian; Lichtenstein, Paul; Anckarsäter, Henrik; Studer, Erik; Suchankova, Petra; Westberg, Lars; Jerlhag, Elisabet ·
RPEP-04545 · 2019The study revealed several key insights into LEAP2-GHSR1a binding:
- LEAP2 and ghrelin bind GHSR1a competitively (sharing the same or overlapping binding sites), contrary to prior reports of non-competitive binding
- LEAP2 shows dual antagonistic behavior depending on timing:
- Added before ghrelin: acts as a non-competitive antagonist (reduces maximal ghrelin effect)
- Added simultaneously with ghrelin: acts as a competitive antagonist (shifts the dose-response curve)
- This unusual pharmacological profile is likely caused by LEAP2's slow dissociation rate from the receptor
- The N-terminal fragment of LEAP2 is critical for receptor binding
- These findings resolve conflicting reports in the literature about LEAP2's mechanism
Wang, Jia-Hui; Li, Hao-Zheng; Shao, Xiao-Xia; Nie, Wei-Han; Liu, Ya-Li; Xu, Zeng-Guang; Guo, Zhan-Yun ·
RPEP-04551 · 2019Ferritin nanoparticles modified with the SpyCatcher protein covalently linked to tumor-specific peptide antigens (via SpyTag) produced 2-3 fold enhanced cytotoxic T cell responses compared to soluble peptide antigens. The nanoparticles rapidly drained to lymph nodes and targeted dendritic cells (especially CD8α+ DCs). When carrying HPV16 E7 peptide or MC38 tumor neoantigen peptides, the vaccine significantly suppressed tumor growth, with further enhancement when combined with PD-1 checkpoint blockade.
Wang, Wenjun; Liu, Zhida; Zhou, Xiaoxiao; Guo, Zhenqian; Zhang, Jing; Zhu, Ping; Yao, Sheng; Zhu, Mingzhao ·
RPEP-04554 · 2019TAT peptide-modified cisplatin-loaded iron oxide nanoparticles (TAT-SPION-CDDP) reversed cisplatin resistance in two nasopharyngeal carcinoma cell lines. The IC50 decreased by an average of 85% in HNE-1/DDP cells and 94% in CNE-2/DDP cells compared to cisplatin alone.
The dual mechanism combined the Fenton reaction from iron oxide (generating reactive oxygen species) with enhanced cellular uptake via the TAT peptide (YGRKKRRQRRR). TAT modification significantly improved intracellular nanoparticle delivery, enabling lower therapeutic doses and potentially reduced side effects.
Weng, Huanhuan; Bejjanki, Naveen Kumar; Zhang, Juan; Miao, Xiangwan; Zhong, Ying; Li, Hailiang; Xie, Huifen; Wang, Siqi; Li, Quanming; Xie, Minqiang ·
RPEP-04558 · 2019VIP-treated dendritic cells (VIP-DC) showed reduced expression of immune activation markers (MHC II, CD40, CD86), decreased interferon-gamma production, and increased IL-4 production compared to untreated dendritic cells (P < 0.05 or 0.01).
When administered to mice with established collagen-induced arthritis, VIP-DC decreased clinical arthritis scores and reduced both bone erosion (P < 0.05) and inflammation (P < 0.01) compared to untreated dendritic cells. VIP-DC performed comparably to Bay 11-7082-induced tolerogenic dendritic cells but showed potentially superior bone protection.
Wu, Huaxiang; Shen, Jingfang; Liu, Lei; Lu, Xiaoyong; Xue, Jing ·
RPEP-04563 · 2019Researchers developed a peptide called EK1 that blocks all human coronaviruses from entering cells by targeting a conserved region (HR1 domain) of the spike protein. EK1 inhibited fusion and cell entry of every human coronavirus tested, with IC50 values of 0.19–0.62 μM — meaning it worked at very low concentrations.
In mice, EK1 protected against HCoV-OC43 infection and provided long-term protection. Crystal structures confirmed the peptide forms stable complexes with HR1 domains from multiple divergent coronaviruses, explaining its broad-spectrum activity.
Xia, Shuai; Yan, Lijue; Xu, Wei; Agrawal, Anurodh S; Algaissi, Abdullah; Tseng, Chien-Te K; Wang, Qian; Du, Lanying; Tan, Wenjie; Wilson, Ian A; Jiang, Shibo; Yang, Bin; Lu, Lu · Preclinical Study (In Vitro + Animal Model)
RPEP-04564 · 2019A missense mutation in the neuropeptide S receptor 1 (NPSR1) gene was identified in humans who naturally sleep less than average. When this mutation was engineered into mice, they also slept less despite having higher sleep pressure — and remarkably, they were resistant to the memory problems that normally accompany sleep deprivation. The mutant receptor showed increased sensitivity to neuropeptide S activation in vivo, suggesting the NPS/NPSR1 signaling pathway plays a critical role in regulating both sleep duration and the link between sleep and memory.
Xing, Lijuan; Shi, Guangsen; Mostovoy, Yulia; Gentry, Nicholas W; Fan, Zenghua; McMahon, Thomas B; Kwok, Pui-Yan; Jones, Christopher R; Ptáček, Louis J; Fu, Ying-Hui ·
RPEP-04570 · 2019The AJICAP method used Fc-binding affinity peptide reagents to introduce thiol functional groups onto three specific lysine residues in native IgG antibodies — without any genetic engineering or antibody modification. A cytotoxic drug was then chemically linked to these thiol groups to create an antibody-drug conjugate.
The resulting HER2-targeting ADC demonstrated selective binding to HER2-positive cells (confirmed by surface plasmon resonance) and effectively killed HER2-positive tumors in an in vivo xenograft mouse model. The method provides site-specific drug attachment starting from any native antibody.
Yamada, Kei; Shikida, Natsuki; Shimbo, Kazutaka; Ito, Yuji; Khedri, Zahra; Matsuda, Yutaka; Mendelsohn, Brian A ·
RPEP-04572 · 2019Substance P (SP) and calcitonin gene-related peptide (CGRP), acting through their receptors NK1R and CRLR/RAMP-1, induced a cascade of cellular transformations in endometriotic tissue: epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), and conversion of stromal cells into smooth muscle cells.
This cascade resulted in increased cell migration, invasiveness, contractility, collagen production, and ultimately fibrosis. Neutralizing NK1R and/or CGRP/CRLR/RAMP-1 signaling abrogated these processes. Deep endometriosis lesions showed significantly higher nerve fiber density, receptor expression, and fibrotic content than ovarian endometriomas, with fibrosis extent correlating positively with receptor staining levels and nerve fiber density.
Yan, Dingmin; Liu, Xishi; Guo, Sun-Wei ·
RPEP-04577 · 2019Exendin-4, a 39-amino acid peptide discovered in Gila monster (Heloderma suspectum) venom, is a full agonist of the GLP-1 receptor with a longer half-life than endogenous GLP-1 due to resistance to DPP-4 enzymatic degradation. Its helical region interacts with the GLP-1 receptor's extracellular N-terminal domain while its C-terminal tryptophan cage enhances binding affinity, switching the receptor from auto-inhibited to auto-activated state. Beyond blood glucose lowering through enhanced β-cell function and GLP-1 receptor upregulation, exendin-4 has shown benefits for neuropathy, nephropathy, and ventricular remodeling. While it has reasonable subcutaneous bioavailability, its half-life remains relatively short, prompting ongoing modifications to improve pharmacokinetics and potency.
Yap, Michelle Khai Khun; Misuan, Nurhamimah ·
RPEP-04589 · 2019A 62-amino-acid peptide (μ-EPTX-Na1a) isolated from Chinese cobra venom selectively blocks the Nav1.8 sodium channel — a key pain-signaling channel in peripheral nerves — through a mechanism never seen before in any other toxin. In rodent models of both inflammatory and neuropathic pain, this peptide relieved pain more potently than morphine.
Critically, μ-EPTX-Na1a showed no evident cytotoxicity, no cardiotoxicity, and no obvious adverse effects even at 30 times the analgesic dose, suggesting a wide safety margin compared to current painkillers.
Zhang, Fan; Zhang, Changxin; Xu, Xunxun; Zhang, Yunxiao; Gong, Xue; Yang, Zuqin; Zhang, Heng; Tang, Dongfang; Liang, Songping; Liu, Zhonghua · Preclinical Discovery
RPEP-04595 · 2019The study established a direct regulatory link between miR-34b/c-5p and NK1R in breast cancer. Key findings across multiple approaches:
- miR-34b/c-5p and truncated NK1R expression in 50 breast cancer patients correlated with tumor stage and Ki67 (proliferation marker)
- Overexpressing miR-34b/c-5p or silencing NK1R suppressed proliferation, induced G2/M arrest, and triggered apoptosis in MDA-MB-231 and MCF-7 breast cancer cells
- The NK1R antagonist aprepitant produced similar anti-cancer effects
- Substance P (the endogenous NK1R agonist) rescued cell growth when miR-34b/c-5p was overexpressed or NK1R was silenced, confirming pathway specificity
- In vivo xenograft models confirmed that miR-34b/c-5p overexpression or NK1R silencing reduced tumorigenicity
Zhang, Lufang; Wang, Lushan; Dong, Dong; Wang, Zhiyong; Ji, Wei; Yu, Man; Zhang, Fei; Niu, Ruifang; Zhou, Yunli ·
RPEP-04601 · 2019In 48 rats divided into sham, ischemia/reperfusion (I/R), and Tβ4 treatment groups (n=16 each):
- Tβ4-treated rats had significantly lower Zea-Longa neurological deficit scores compared to I/R controls
- Tβ4 significantly reduced neuronal apoptosis (TUNEL-positive cells) compared to I/R group
- Tβ4 significantly increased GRP78 expression (a protective endoplasmic reticulum chaperone)
- Tβ4 significantly decreased CHOP and caspase-12 expression (pro-apoptotic ER stress markers)
- These changes indicate Tβ4 protects neurons by modulating the endoplasmic reticulum stress response pathway
Zhang, Zhongsheng; Liu, Shuangfeng; Huang, Sichun ·
RPEP-04621 · 2020Molecular dynamics simulations revealed that GF-17 penetrated pure DPPG membranes (mimicking negatively charged bacterial surfaces) more favorably than mixed DPPE/DPPG membranes. The potential of mean force (PMF) calculation showed no energy barrier for GF-17 crossing through the center of the DPPG bilayer — meaning the peptide encounters no thermodynamic resistance when penetrating bacterial membranes.
The peptide increased the area per lipid and lateral diffusion of lipids (indicating membrane disruption and increased fluidity) but did not significantly affect bilayer thickness. GF-17 adopted a more compact and rigid structure in pure DPPG membranes compared to mixed membranes. The dominant secondary structures were α-helix and coil in both membrane types.
Aghazadeh, Hossein; Ganjali Koli, Mokhtar; Ranjbar, Reza; Pooshang Bagheri, Kamran ·
RPEP-04623 · 2020Hydrolyzed collagen (HC) — collagen broken down into small peptides — shows dual benefits for skin when taken orally or applied topically. Oral ingestion increases collagen-derived peptide levels in the blood and improves measurable skin properties including elasticity, moisture retention, and transepidermal water loss. Daily oral HC intake also protects against UV-induced melasma, boosts fibroblast production, and enhances the skin's extracellular matrix.
Topically, HC works as a safe cosmetic ingredient with effective moisturizing properties at the outermost skin layer (stratum corneum), reducing visible signs of aging like dryness, laxity, and wrinkles. The antioxidant activity of collagen peptides depends on their size — smaller peptides have greater free radical scavenging ability — and is driven by hydrophobic and aromatic amino acids in the peptide chain.
Aguirre-Cruz, Gabriel; León-López, Arely; Cruz-Gómez, Verónica; Jiménez-Alvarado, Rubén; Aguirre-Álvarez, Gabriel · Review
RPEP-04624 · 2020The synthetic natriuretic peptide NPCdc, derived from rattlesnake venom, decreased mean arterial pressure and NADPH oxidase activity while increasing glomerular filtration rate, fractional sodium excretion, and nitric oxide levels in both control and nephrectomized rats. These effects were mediated through nitric oxide and components of natriuretic peptide receptor C (NPR-C) signaling, specifically involving ERK1/2 phosphorylation at Thr-202/Tyr-204.
The peptide was infused at 7.5 μg/kg/min for 70 minutes, producing beneficial cardiovascular and renal effects even in rats with reduced kidney mass (5/6 nephrectomy), suggesting potential therapeutic application for cardiorenal syndrome.
Aires, Regina S; Vieira, Leucio D; Freitas, Ana C N; de Lima, Maria E; Lima, Natalia K S; Farias, Juliane S; Paixão, Ana D ·
RPEP-04626 · 2020All four mediators (NKA, SP, IL-8, MMP-8) were significantly higher in pulpitis pulp tissue compared to healthy pulp (NKA: P<0.001, SP: P=0.005, IL-8: P<0.001, MMP-8: P<0.001). The same pattern was seen in gingival crevicular fluid (NKA: P=0.01, SP: P<0.001, IL-8: P=0.001, MMP-8: P<0.001). One week after root canal treatment, all mediator levels decreased significantly in GCF. SP, IL-8, and MMP-8 levels were higher in patients with higher pain scores than those with lower pain scores.
Akbal Dincer, Gozde; Erdemir, Ali; Kisa, Ucler ·
RPEP-04627 · 2020All three CGRP monoclonal antibodies significantly reduced monthly migraine days compared to placebo at every time point measured: by 2.07 days at 4 weeks, 1.78 days at 8 weeks, and 1.80 days at 12 weeks (all p<0.001). These effects were consistent across erenumab 70 mg, fremanezumab 225 mg, and galcanezumab 120 mg individually.
Beyond migraine day reduction, patients on active treatment used fewer acute migraine medications and had significantly higher rates of achieving a 50% or greater reduction in migraine frequency. Treatment-related adverse events showed no significant difference between active treatment and placebo groups.
Alasad, Yousef Waleed; Asha, Mohammad Zaki ·
RPEP-04631 · 2020Researchers used mRNA display screening to discover a new series of cyclic peptides that block the interaction between PCSK9 and the LDL receptor — the same target hit by existing injectable antibody drugs like evolocumab and alirocumab. Through structure-based drug design, they optimized these peptides into smaller, more metabolically stable bicyclic compounds (such as compound 78) that could potentially be developed into oral, once-daily PCSK9 inhibitors for lowering cholesterol.
Alleyne, Candice; Amin, Rupesh P; Bhatt, Bhavana; Bianchi, Elisabetta; Blain, J Craig; Boyer, Nicolas; Branca, Danila; Embrey, Mark W; Ha, Sookhee N; Jette, Kelli; Johns, Douglas G; Kerekes, Angela D; Koeplinger, Kenneth A; LaPlaca, Derek; Li, Nianyu; Murphy, Beth; Orth, Peter; Ricardo, Alonso; Salowe, Scott; Seyb, Kathleen; Shahripour, Aurash; Stringer, Joseph R; Sun, Yili; Tracy, Rodger; Wu, Chengwei; Xiong, Yusheng; Youm, Hyewon; Zokian, Hratch J; Tucker, Thomas J · Preclinical Drug Development
RPEP-04640 · 2020Anti-CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) reduced monthly migraine days in both chronic and episodic migraine with minimal clinically significant adverse events. Evidence also supports efficacy in refractory migraine patients despite optimal existing prophylaxis. This is the first target-specific migraine prophylaxis drug class — previous preventives were all repurposed from other indications and had poor side effect profiles.
Arca, Karissa; Reynolds, Jenna; Sands, Kara A; Shiue, Harn J ·
RPEP-04648 · 2020The researchers successfully produced recombinant GLP-1 with a non-natural amino acid (p-azido-L-phenylalanine) incorporated at three specific positions (V16, Y19, and F28), then conjugated human serum albumin (HSA) at each site using click chemistry (strain-promoted azide-alkyne cycloaddition).
All three HSA-conjugated GLP-1 variants achieved comparable extended serum half-lives in vivo. However, their biological activities differed significantly: the variants showed different in vitro receptor activation and different glucose-lowering effects in vivo, demonstrating that the specific site of albumin attachment critically affects therapeutic function even when half-life extension is equivalent.
Bak, Mijeong; Park, Junyong; Min, Kiyoon; Cho, Jinhwan; Seong, Jihyoun; Hahn, Young S; Tae, Giyoong; Kwon, Inchan ·
RPEP-04650 · 2020NK1R antagonist treatment (L-732,138) in rats performing a high repetition high force (HRHF) task produced multiple beneficial effects compared to untreated HRHF rats:
- Improved grip strength (reversed task-induced decline)
- Reduced mechanical sensitivity and temperature aversion (pain measures)
- Reduced flexor digitorum epitendon thickening
- Decreased HRHF-induced increases of fibrotic markers TGFβ1, CCN2/CTGF, and collagen type 1 in flexor digitorum muscles
- Reduced task-induced collagen deposition in forepaw upper dermis
These findings demonstrate that Substance P-NK1R signaling drives fibrogenic responses and associated pain in overuse injuries across multiple tissue types (tendon, muscle, skin).
Barbe, M F; Hilliard, B A; Fisher, P W; White, A R; Delany, S P; Iannarone, V J; Harris, M Y; Amin, M; Cruz, G E; Popoff, S N ·
RPEP-04656 · 2020Whole-exome sequencing of 159 surgically removed pituitary adenomas revealed that somatic copy number alterations (SCNAs) — not point mutations — are the hallmark of hormone-secreting pituitary tumors. In growth hormone-secreting tumors specifically, cAMP signaling and DNA damage repair pathways were both affected.
The key discovery: cAMP, the same signaling molecule that drives GH secretion and cell growth, simultaneously causes DNA damage. This creates a vicious cycle where hormone overproduction and genomic instability are mechanistically linked. Octreotide, a somatostatin analog used to treat acromegaly, inhibited cAMP and reversed the DNA damage — suggesting treatment may address the tumor biology, not just the hormone excess.
Ben-Shlomo, Anat; Deng, Nan; Ding, Evelyn; Yamamoto, Masaaki; Mamelak, Adam; Chesnokova, Vera; Labadzhyan, Artak; Melmed, Shlomo · Lab Study
RPEP-04660 · 2020Combining the oral CGRP receptor antagonist rimegepant (75 mg as needed) with injectable CGRP monoclonal antibodies (erenumab, fremanezumab, or galcanezumab) for migraine was well tolerated in 13 patients over approximately 10 weeks. A total of 224 rimegepant doses were taken. Five patients (38%) reported mild adverse events, most commonly nasopharyngitis. Three patients had mild-to-moderate events considered potentially treatment-related. No serious adverse events, no treatment discontinuations, and no liver enzyme elevations occurred. This provides the first systematic safety data for using two different CGRP-targeting therapies simultaneously.
Berman, Gary; Croop, Robert; Kudrow, David; Halverson, Philip; Lovegren, Meghan; Thiry, Alexandra C; Conway, Charles M; Coric, Vladimir; Lipton, Richard B · Open Label Safety Substudy
RPEP-04661 · 2020Primary outcome: No significant treatment-specific improvement in social responsiveness (Social Responsiveness Scale). Both oxytocin and placebo groups showed improvement, with no significant between-group difference (self-report p=0.37, informant-rated p=0.19).
Secondary outcomes with significant treatment-specific effects:
- Repetitive Behavior Scale: Reduced self-reported repetitive behaviors in oxytocin group (p=0.04), persisting up to 1 month and even 1 year post-treatment
- State Adult Attachment Measure: Reduced feelings of avoidance toward others (p=0.03), lasting up to 1 year
- Profile of Mood States: Higher reports of vigor (energy, activity, liveliness) in oxytocin group (p=0.03)
These secondary benefits persisted well beyond the 4-week treatment period, suggesting potential long-lasting neuroplastic effects.
Bernaerts, Sylvie; Boets, Bart; Bosmans, Guy; Steyaert, Jean; Alaerts, Kaat ·
RPEP-04665 · 2020This review consolidates evidence that thymosin beta-4 (Tβ4) promotes cardiac tissue repair through multiple mechanisms. Tβ4 activates resident epicardial progenitor cells — stem-like cells sitting on the heart's surface — and modulates inflammatory injury, both of which promote the survival of cardiomyocytes (heart muscle cells) after myocardial infarction.
Beyond the heart, the review notes Tβ4's roles in tissue repair after stroke, in peripheral and central nervous system remodeling, and in skeletal muscle recovery. It may work synergistically with other repair-promoting factors including melatonin and C-fiber-derived peptides.
Bjørklund, Geir; Dadar, Maryam; Aaseth, Jan; Chirumbolo, Salvatore · Narrative Review
RPEP-04672 · 2020The study demonstrates that cis-urocanic acid, previously not known as a significant copper binder, can coordinate Cu(II) ions. More importantly, GHK and cis-urocanic acid can both bind to the same Cu(II) ion simultaneously, forming a ternary complex [GHK][Cu(II)][cis-urocanic acid].
Based on the natural concentrations of these three molecules in human tissues (particularly skin and plasma) and the binding affinities measured, the authors conclude that this ternary complex likely exists in the body and may be partly responsible for the biological effects previously attributed to GHK or urocanic acid individually.
Bossak-Ahmad, Karolina; Wiśniewska, Marta D; Bal, Wojciech; Drew, Simon C; Frączyk, Tomasz ·
RPEP-04673 · 2020Researchers used mRNA display — a technique that screens trillions of peptide variants simultaneously — to discover cyclic peptides capable of penetrating biological membranes. The top hit, cyclo[Glut-MRKRHASRRE-K*], successfully penetrated both fruit fly embryos and mammalian cells (human embryonic stem cells and mouse fibroblasts). This is notable because no previously known peptide could cross both cytoplasmic membranes and the tough outer embryonic membrane. The cyclic version significantly outperformed its linear (non-cyclized) counterpart.
Bowen, John; Schloop, Allison E; Reeves, Gregory T; Menegatti, Stefano; Rao, Balaji M ·
RPEP-04678 · 2020From 30 identified randomized clinical trials, three studies met inclusion criteria for indirect treatment comparison (one each for erenumab, fremanezumab, and eptinezumab). Using Bucher's method for adjusted indirect comparison:
- No statistically significant differences in the proportion of patients achieving ≥50% reduction in monthly migraine days between any of the three drugs
- Most of the 95% confidence intervals fell within the calculated equivalence delta margin (Δ = 9.5%)
- No relevant safety differences were found among the three drugs
- The drugs were assessed as probable clinical equivalents in terms of efficacy and safety for chronic migraine prevention
Briceño-Casado, María Del Pilar; Gil-Sierra, Manuel David; Fénix-Caballero, Silvia ·
RPEP-04679 · 2020The article identifies five patient populations most likely to benefit from oral semaglutide: (1) patients with inadequate glycemic control on one or more oral medications; (2) patients who would benefit from weight loss; (3) patients at risk of hypoglycemia; (4) patients who would be candidates for injectable GLP-1RAs but prefer oral therapy; and (5) patients on basal insulin needing treatment intensification.
Critical administration requirements include: swallowing the tablet whole with no more than 4 oz (120 mL) of plain water on an empty stomach upon waking, then waiting at least 30 minutes before eating, drinking, or taking other oral medications. Food and excess liquid significantly reduce absorption. Gradual dose escalation is recommended to minimize gastrointestinal side effects.
Brunton, Stephen A; Mosenzon, Ofri; Wright, Eugene E ·
RPEP-04683 · 2020Four monoclonal antibodies targeting the CGRP pathway have been approved for migraine prevention:
- Erenumab: targets the CGRP receptor
- Galcanezumab: targets the CGRP peptide
- Fremanezumab: targets the CGRP peptide
- Eptinezumab: targets the CGRP peptide
These are the first drugs specifically developed for migraine prevention, replacing reliance on repurposed medications from other therapeutic areas.
Bucklan, Julia; Ahmed, Zubair ·
RPEP-04686 · 2020The human body has a sophisticated built-in pain relief system that uses endogenous peptides and neurotransmitters — including enkephalins (met- and leu-enkephalin), β-endorphin, dynorphins, endocannabinoids, noradrenaline, dopamine, serotonin, and ATP — working through multiple receptor types (α2-adrenergic, μ-opioid, and others) to modulate pain signaling.
The review maps how these natural pain-relieving molecules interact within the descending pain modulation pathways, with particular focus on neuropathic pain caused by nerve injury, diabetes, or chemotherapy. It also examines why excessive exogenous opioid use creates problems through the sympathetic nervous system, contributing to the opioid crisis.
Notably, while the US and Canada experienced a severe opioid crisis, most European countries did not — despite also increasing pain medication use — suggesting that prescribing practices and regulatory frameworks, not just pain prevalence, drive opioid misuse.
Bán, E Gy; Brassai, A; Vizi, E S · Review
RPEP-04690 · 2020Pooling data from 7 cardiovascular outcome trials (CVOTs) enrolling 56,004 type 2 diabetes patients, GLP-1 receptor agonists showed no increased risk of acute pancreatitis (Peto OR 1.05, 95% CI 0.78–1.40, p=0.76) or pancreatic cancer (Peto OR 1.12, 95% CI 0.77–1.63, p=0.56) compared to placebo. Results were robust across sensitivity analyses. A total of 180 cases of acute pancreatitis and 108 cases of pancreatic cancer occurred across all trials, with median follow-up ranging from 1.3 to 5.4 years.
Cao, Chuqing; Yang, Shuting; Zhou, Zhiguang ·
RPEP-04691 · 2020Using mouse vaccination studies, the researchers demonstrated that the position of a mutation within a neoantigen peptide is an important criterion for predicting immunogenicity. While computational methods have made progress in predicting which peptides will be presented by the immune system, understanding which mutated peptides are actually recognized as foreign by T cells has remained a major gap. This work identifies mutation position as a key variable that can improve neoantigen prediction algorithms.
Capietto, Aude-Hélène; Jhunjhunwala, Suchit; Delamarre, Lélia ·
RPEP-04703 · 2020Blocking the ghrelin receptor (GHS-R1A) with the antagonist JMV2959 significantly reduced cannabinoid-induced dopamine release in the nucleus accumbens shell — the brain's reward center and a critical trigger for addiction. JMV2959 pretreatment also attenuated cannabinoid-increased endocannabinoid levels (anandamide and 2-AG), reversed cannabinoid-induced GABA decreases, and reduced cannabinoid-triggered behavioral stimulation. This demonstrates that the ghrelin peptide system significantly participates in the rewarding and reinforcing effects of cannabinoids.
Charalambous, Chrysostomos; Lapka, Marek; Havlickova, Tereza; Syslova, Kamila; Sustkova-Fiserova, Magdalena ·
RPEP-04711 · 2020Synthetic long peptide (SLP) neoantigen vaccines offer several advantages over traditional short peptide vaccines: they overcome immune tolerance, activate both CD4+ helper and CD8+ killer T cell responses, and target mutations unique to individual tumors rather than shared antigens.
The review summarizes evidence that extending short peptides (8-10 amino acids) into longer formats (25-35 amino acids) improves antigen processing by professional antigen-presenting cells and generates more robust and durable immune responses. Multiple preclinical and early clinical studies have shown encouraging results with personalized neoantigen peptide vaccines.
Chen, Xiaotong; Yang, Ju; Wang, Lifeng; Liu, Baorui ·
RPEP-04712 · 2020Two photoreactive excipient analogs — photo-leucine (pLeu, an amino acid analog) and photo-glucosamine (pGlcN, a sugar analog) — showed distinctly different labeling patterns on salmon calcitonin in lyophilized solids. The extent and specific sites of labeling on the peptide differed between the two probes, demonstrating that ionizable and nonionizable excipients interact with the peptide through different mechanisms.
The distribution of photo-reaction products was also influenced by the type of unlabeled excipient present (sucrose vs. histidine) and the pre-lyophilization pH (tested from 6 to 9.9), indicating that formulation conditions meaningfully change how excipients contact the peptide in the solid state.
Chen, Yuan; Topp, Elizabeth M ·