urocortin II (NBI-69734) / Renova Therap - LARVOL DELTA

Argostemma sawmlianae (Rubiaceae, Argostemmateae), a new species from Northeast India under the Indo-Burma Hotspot. (PubMed, PhytoKeys) - "The molecular analyses based on matK (cpDNA) and ITS2 (nrDNA) sequences support the morphological evidences confirming A. sawmlianae as a distinct new species. The newly discovered species is provisionally categorized as Critically Endangered (CR) in accordance with the IUCN Red List Categories and Criteria (IUCN 2024) based on available data."

Journal

Identification of oxidative stress-responsive genes in recurrent miscarriage and their role in disease pathogenesis. (PubMed, PLoS One) - "Bioinformatics techniques, which led to the identification of six hub genes-ARRB2, BMF, SORCS2, STK3, UCN2, and VIPR1-as potential biomarkers for RM, elucidated the biological processes and molecular functions associated with genes that are differentially expressed under oxidative stress...Furthermore, immunohistochemical (IHC) analysis on endometrial tissues from RM patients and matched controls confirmed significantly elevated protein expression levels of six hub genes in the RM group, consistent with the bioinformatics findings. This study establishes a diagnostic model and provides insights into immune-modulation therapies for RM."

Journal • Breast Cancer • Immune Modulation • Immunology • Liver Cancer • Oncology • Solid Tumor • CD8 • TGFB1

First in class CRF2 receptor agonist COR-1167, reduces decompensation, improves exercise capacity, cardiac and renal function on top of Empagliflozin in the ZSF-1 rat model of worsening heart failure with preserved ejection fraction (AHA 2025) - "Urocortin-2 (UCN-2) peptide which is part of the corticotropin-releasing factor (CRF) family, is a paracrine CRF2 receptor agonist that protects heart and kidney function in various HF models and in HF patients. On a background of volume overload and Empa treatment, daily s.c. delivery of COR-1167 maintained CO, rapidly ameliorated decompensation and deteriorating heart and kidney function in ZSF-1 rats. Chronic CRF2 agonism with COR-1167 is a potential new therapy to treat patients with WHF and preserved ejection fraction."

Late-breaking abstract • Preclinical • Cardiovascular • Congestive Heart Failure • Glomerulonephritis • Heart Failure • KIM1

Discovery of HM17321: A Novel CRFR2 Selective and Biased UCN2 Analog for High-Quality Weight Loss (OBESITY WEEK 2025) - "HM17321, a novel long-acting, CRFR2-selective, and biased UCN2 analog, demonstrates significant potential as next-generation obesity and related metabolic disease medication. The synergy between the mechanistic goals for metabolic improvement and the structural insights into the involved molecules, coupled with the strategic application of AI technologies, led to the design of a promising therapeutic candidate. This seamless integration of computational tools and biological knowledge highlights the significant impact of collaborative approaches in driving progress in drug development."

Genetic Disorders • Metabolic Disorders • Obesity

HM17321 Promotes High-Quality Weight Loss and Improves Metabolic Health in Obesity Treatment (OBESITY WEEK 2025) - "Urocortin-2 (UCN2) has been proposed to promote muscle hypertrophy and lipolysis, which may contribute to improved weight loss quality (WLQ) and whole-body metabolism through the preservation of lean mass. HM17321 demonstrated a unique profile by achieving high-quality weight loss through favorable body re-composition, especially characterized by increased lean mass. In addition, HM17321 provided metabolic benefits such as enhanced energy expenditure and improved glycemic control, supporting the fact that HM17321 enhances not only muscle mass, but also its metabolic functionality. These findings position HM17321 as a promising next-generation therapeutic candidate for obesity and related metabolic disorders, with the potential to be used in combination with incretin-based therapies."

Genetic Disorders • Metabolic Disorders • Obesity

Blood and Muscle Proteomic Analysis Reveals Muscle-Preserving Effects of HM17321 in Mouse Model (OBESITY WEEK 2025) - "HM17321 is a novel corticotropin-releasing factor receptor 2 (CRFR2)-selective and biased urocortin-2 (UCN2) analog that has exhibited dual effects of fat mass loss and lean mass gain in diet-induced obesity (DIO) mouse model. Proteomic analysis in this study suggests that HM17321 directly acts on skeletal muscle to increase muscle mass and improve metabolism, irrelevant with its weight loss effect. These findings highlight its potential to improve the weight loss quality, supporting HM17321 as a next generation therapeutic option for obesity management."

Omic analysis • Preclinical • Genetic Disorders • Obesity

7031: Cheers and Challenges: Game On! (for APPs) (CHEST 2025) - "This is a free event, but we ask that you RSVP in advance. https://share.hsforms.com/1EmbG7v6jSr2SY8uCN2xx4Q1o2m1 CHEST gratefully acknowledges Boehringer Ingelheim as a Platinum Sponsor and United Therapeutics as a Silver Sponsor."

Dendrocalamus wazibii (Poaceae, Bambusoideae), a new bamboo species from Yunnan, China. (PubMed, PhytoKeys) - "The morphology of this new species is similar to D. peculiaris and D. tomentosus, but can be easily distinguished from them by having culm leaf ligule 15 mm long (vs. 5-7 mm in D. tomentosus and 6-10 mm in D. peculiaris), linear culm leaf auricle (vs. absent in D. tomentosus and D. peculiaris), anther 2-2.5 mm long (vs. 2.5-3 mm in D. tomentosus; vs. 3-3.5 mm in D. peculiaris), stamen 5 mm long (vs. 6 mm in D. tomentosus; vs. 10 mm in D. peculiaris). According to the IUCN Red List Categories and Criteria (IUCN 2024), it meets the criteria to be listed as Data Deficient (DD)."

Journal

The effects of UCN2 on neural cell function of spinal cord injury rats facilitate post-injury neuronal regeneration. (PubMed, Cell Signal) - "Complementary in vitro experiments confirmed that UCN2 directly promotes axonal regeneration, inhibits neuronal apoptosis, enhances the secretion of GDNF from astrocytes, and suppresses the inflammatory NF-κB pathway in microglia. In conclusion, UCN2 facilitates axonal regeneration and functional recovery in SCI by activating the cAMP-PKA pathway, which in turn modulates neuronal survival, glial phenotype, and neuroinflammation, highlighting its significant therapeutic potential."

Journal • Preclinical • CNS Disorders • Inflammation • Orthopedics • BCL2 • RHOA

Exploratory safety investigations in normal, freely moving Göttingen minipigs using telemetry: Pharmacological validation. (PubMed, J Pharmacol Toxicol Methods) - "The study highlights different CV study designs in Göttingen Minipigs and show that this model qualitatively reproduced the CV effects observed in humans following treatment with the three test compounds. These data support the minipig as a translational preclinical model for exploratory safety evaluations, although the magnitude of the changes may not translate completely between species."

Journal • Cardiovascular

Gold Nanoparticles-Functionalized Ultrathin Graphitic Carbon Nitride Nanosheets for Boosting Solar Hydrogen Production: The Role of Plasmon-Induced Interfacial Electric Fields. (PubMed, Molecules) - "The Au/UCN-20 Schottky junction exhibits exceptional photocatalytic activity, achieving a hydrogen evolution rate (14.2 mmol·g-1 over a 4 h period) while maintaining robust stability through five consecutive photocatalytic cycles...The interfacial electric field generated at the Au /UCN heterojunction is proposed to enhance charge-transfer efficiency through Schottky barrier penetration of photocarriers, mediated by electric field-driven carrier migration, according to surface potential and finite-difference time-domain (FDTD). These findings uncover a previously obscured photocatalytic mechanism driven by LSPR-induced interfacial electric fields, pioneering a quantum-dot-directed strategy to precisely engineer charge dynamics in advanced photocatalysts via targeted manipulation of nanoscale electric field effects."

Journal

Fargesianana (Poaceae, Bambusoideae), a new bamboo species from Yunnan, China. (PubMed, PhytoKeys) - "Hitherto, this new species is the smallest of Fargesia species found and recorded. According to the IUCN Red List Categories and Criteria (IUCN 2024), it meets the criteria to be listed as Critically Endangered (CR)."

Journal

Machine Learning Characterization of Immunometabolism in the Tumor Microenvironment and Immunotherapy Responses in Bladder Cancer. (PubMed, J Immunother) - "Furthermore, by silencing the expression of UCN2, we observed a significant reduction in the proliferation, migration, and invasion of BLCA cells in vitro. UCN2 is considered a crucial gene in IMB that plays a significant role in the onset and development of BLCA."

Biomarker • IO biomarker • Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Pathophysiological and therapeutic implications of urocortin-2 in heart failure with preserved ejection fraction (HEART FAILURE 2025) - "This work suggests that Ucn-2/CRHR2 system is altered in experimental HFpEF and that chronic administration of Ucn-2 attenuates LV dysfunction and remodeling, in particular the hypertrophic changes of the cardiac muscle."

Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertension • COL3A1 • TNFA • UCN

Urocortin2 measurement for heart failure assessment. (PubMed, Sci Rep) - "The assay showed that blood UCN2 values indicated a negative relationship with cardiac ejection fraction in 52 patients with heart failure. Blood UCN2 levels were not correlated with brain natriuretic peptide, a standard marker of heart failure, and were higher in patients with cardiomyopathy than in those with heart failure, suggesting that measuring blood UCN2 levels may be a novel test for assessing the pathophysiology of heart failure."

Biomarker • Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • GPRC6A • NPPB

Carexyankouensis, a new species of Cyperaceae from limestone landform in northern Guangdong, China. (PubMed, PhytoKeys) - "The new species is similar to C.brevicuspis C. B. Clarke, but differs in having shorter culms (10-15 cm vs 20-55 cm) and spikes (1-1.5 cm vs 3.7-7 cm), leaves wider (15-20-35 mm vs 5-10 mm) and lighter colored (pale green or yellow-green vs dark green), nutlet beak oblique (vs erect or slightly curved), and slightly thickened (vs thickened) style base. Following the IUCN Red List Criteria (IUCN 2024), Carexyankouensis is assessed as 'Data Deficient (DD)'."

Journal

Electroacupuncture Improves the Motor Function in Rats with Spinal Cord Injury by Regulating UCN2-Mediated cAMP-PKA Signaling in the Spinal Cord Microenvironment. (PubMed, Cell Mol Neurobiol) - "This process improves the presence of astrocytes and microglia around the injury site, inhibits neuronal apoptosis, and increases the number of myelin sheaths and NF. As a result, hind-limb locomotor ability is restored in rats with SCI."

Journal • Preclinical • CNS Disorders • Orthopedics • MBP

Osmoregulatory contributions of the corticotropin-releasing factor system in the intestine of Atlantic salmon. (PubMed, J Exp Biol) - "Similar increases in UCN2 and CRFR2 were observed following seawater to freshwater transfer of post-smolts. Our results indicate that the intestinal CRF system of Atlantic salmon contributes to osmoregulation during the initial days following changes in environmental salinity and that osmoregulatory actions of the intestinal CRF system are conserved across vertebrates."

Journal

Suppression of luteinizing hormone secretion in female mice by a Urocortin 2 - CRHR2 signaling pathway. (PubMed, Endocrinology) - "Together these data demonstrate that UCN2-CRHR2 signaling disrupts the pulsatile and surge modes of LH secretion via direct suppression of kisspeptin cells. Furthermore, these findings suggest UCN2 cells in the PVN are regulated by metabolic stress and brainstem norepinephrine signaling pathways that convey stress cues to the hypothalamus."

Journal • Preclinical • Hypoglycemia • FOS

Antimicrobial Neuropeptides and Their Receptors: Immunoregulator and Therapeutic Targets for Immune Disorders. (PubMed, Molecules) - "This review examines 10 antimicrobial neuropeptides, including pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), α-melanocyte stimulating hormone (α-MSH), ghrelin, adrenomedullin (AM), neuropeptide Y (NPY), urocortin II (UCN II), calcitonin gene-related peptide (CGRP), substance P (SP), and catestatin (CST). Their expression characteristics and the immunomodulatory mechanisms mediated by their specific receptors are summarized, along with potential drugs targeting these receptors. Future studies should focus on further investigating antimicrobial neuropeptides and advancing the development of related drugs in preclinical and/or clinical studies to improve the treatment of immune-related diseases."

Journal • Review • Immunology • ADCYAP1 • ADM

The effects of corticotropin-releasing factor (CRF) and urocortins on the serotonin (hydroxytryptamine, 5HT) released from the raphe nuclei (RN). (PubMed, Neuropeptides) - "Corticotropin-releasing factor (CRF) and urocortins (UCN1, UCN2 and UCN3) belong to the same CRF family of neuropeptides...Our results indicate the existence of two apparently opposing CRF systems in the RN: activation of CRF1 by CRF and UCN1 may inhibit, whereas activation of CRF2 by UCN3 may stimulate the 5HT release. The dysbalance between CRF1 and CRF2 activation and, consequently, alteration of serotoninergic signalling may result in anxiety and depression, associated with hyperactivity of the HPA axis."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Mesoporous NiFe2O4@g-C3N4-based p-n Heterostructures for Boosting Solar-Driven Photocatalytic Dye Degradation and Hydrogen Evolution. (PubMed, Chem Asian J) - "Notably, mp-NiF@uCN-20% with 1.0 wt% of Pt loading achieves the highest H2 evolution rate of 2294 µmolg⁻¹h⁻¹, which is 3.72, 1.52, and 13.49 times higher than that of pure CN, p-uCN, and NiFO, respectively...Further, the magnetic nanocomposite exhibits remarkable stability even after multiple runs, indicating their reusability. The experimental findings emphasize the importance of p-n heterojunctions, interfacial band alignment, and mesoporous architecture in enhancing the photocatalytic efficiency of NiFe2O4@g-C3N4 nanocomposites."

Journal

Regulation and function of the gill corticotropin-releasing factor system during osmoregulatory disturbances in Atlantic salmon. (PubMed, J Exp Biol) - "Most CRF system components were expressed in the gills with CRF receptor 2 (crfr2a), CRF binding protein (crfbp1 and crfbp2), and urocortin 2 (ucn2a) being the most abundant...Indeed, activation of the CRF system in cultured filaments from freshwater-acclimated (but not seawater-acclimated) salmon had transcriptional effects on several physiological systems (e.g., endothelial permeability, angiogenesis, and immune regulation) which involved contributions by both CRF receptor subtypes. Overall, our results indicate that the gill CRF system is more active in hypoosmotic environments and directly contributes to the coordination of physiological responses following osmotic disturbances."

Journal

Antimicrobial neuropeptides and their therapeutic potential in vertebrate brain infectious disease. (PubMed, Front Immunol) - "This review systematically examines 12 neuropeptides, pituitary adenylate cyclase-activating peptide (PACAP), vasoactive intestinal peptide (VIP), α-melanocyte stimulating hormone (α-MSH), orexin-B (ORXB), ghrelin, substance P (SP), adrenomedullin (AM), calcitonin-gene related peptide (CGRP), urocortin-II (UCN II), neuropeptide Y (NPY), NDA-1, and catestatin (CST), identified for their antimicrobial properties, summarizing their structural features, antimicrobial effectiveness, and action mechanisms...However, the connection between this anti-inflammatory property and the brain's infection defense strategy has rarely been explored. Our review suggests that the combined antimicrobial and anti-inflammatory actions of neuropeptides could be integral to the brain's defense strategy against pathogens, marking an exciting direction for future research."

Journal • Review • Infectious Disease • Inflammation • ADCYAP1 • ADM

A novel Urocortin-2 analog COR-1167 corrects cardiac and renal dysfunction on top of Empagliflozin in a rat model of acute decompensated heart failure (AHA 2024) - "Introduction: Urocortin-2 (UCN-2) is a peptide belonging to the corticotropin-releasing factor family that has cardiovascular, renal, metabolic and anti-inflammatory actions and improves cardiac function in human heart failure (HF) and cardiorenal dysfunction in chronic HF models. In the setting of ADHF, significant cardiorenal benefits and decongestion occurred when COR-1167 was administered on top of an SGLT2 inhibitor."

Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Nephrology • Renal Disease