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

Mechanism analysis of MPTP-induced Parkinson's disease-like pathology via the HPA axis-microglial glucocorticoid receptor pathway. (PubMed, Ecotoxicol Environ Saf) - "Notably, pharmacological activation of the HPA axis with Urocortin III counteracted the protective effects of EA, resulting in renewed DA neuron loss, reduced microglial GR expression, and exacerbated neuroinflammation...EA reversed these pathological changes. These findings provide new insights into the pathogenesis of environmental neurotoxin-induced PD."

Journal • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • IL10 • IL1B • IL6 • NR3C1 • TNFA

Prognostic and exploratory neurohormonal correlates of hypochloraemia in heart failure: a multicentre cohort study. (PubMed, Heart) - "Hypochloraemia identified patients with heart failure at substantially increased cardiovascular risk independent of established prognostic markers. Exploratory analyses suggested a potential association between circulating UCN2 and chloride homeostasis that warrants mechanistic investigation."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

CRHR2 activation by urocortins regulates splenic microbiota-immune-brain axis in a single prolonged stress model of post-traumatic stress in male rats. (PubMed, Neuropeptides) - "Neuroinflammatory markers in the vHipp correlated with splenic microbiota and inflammatory markers. Overall, these findings suggest that CRHR2 stimulation by intranasal UCN2/UCN3 administration prevents PTSD-induced alterations through interconnected effects on splenic microbiota composition, peripheral immune responses, and hippocampal synaptic plasticity and neuroinflammatory markers."

Journal • Preclinical • CNS Disorders • Inflammation • Mood Disorders • Post-traumatic Stress Disorder • CD69 • CX3CR1 • DCX • IL1B

Contribution to Charophyceae knowledge in Slovakia - re-discovery of Nitella gracilis. (PubMed, Biodivers Data J) - "At the second locality, phytosociological relevés were recorded around stands dominated by N. gracilis and classed as the association Nitelletum gracilis. Based on the limited number of confirmed sites, we propose changing its national Red List status from Regionally Extinct (RE) to Endangered (EN (B1, B2a, c)) (IUCN 2012a, IUCN 2012b, IUCN 2024)."

Journal

Stress, mood, and Parkinson's disease: selective dysregulation of corticotropin-releasing hormone and urocortin neurocircuits. (PubMed, Geroscience) - "We investigated region-specific alterations of corticotropin-releasing hormone (CRH) family neuropeptides in a rotenone-induced rat model of PD and evaluated the effects of combined dopaminergic (benserazide/L-DOPA) and antidepressant (fluoxetine) treatment. Motor performance, anhedonia-like behavior, dopaminergic neurodegeneration, and CRH-, urocortin 1 (UCN1)-, urocortin 2 (UCN2)-, and urocortin 3 (UCN3)-related molecular changes were assessed using behavioral testing, immunohistochemistry, and RNAscope in situ hybridization...These findings identify selective vulnerability of hypothalamic stress-regulatory neuropeptide circuits in experimental PD and suggest that aging-related impairment of stress resilience may contribute to affective non-motor symptoms. Beyond providing a comprehensive neuroanatomical characterization of CRH-family peptide alterations, this work highlights region-specific neuropeptide signaling as a potential framework for developing more precise..."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Multi-omics analysis of kidney renal cell carcinoma in silico with preliminary in vivo validation. (PubMed, Front Immunol) - "The CRHBP-UCN2 axis critically regulates KIRC prognosis and immune microenvironment remodeling. CRHBP serves as a reliable prognostic biomarker and a potential anticancer peptide target, while dabrafenib is a promising therapeutic agent for KIRC."

Biomarker • IO biomarker • Journal • Preclinical • Clear Cell Carcinoma • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • SRGN • TYROBP

Stress Receptors and Glucose Metabolism: CRF2 as A Critical Regulator of Pancreatic Islet Function (ENDO 2026) - "While UCN2 and UCN3 are known to regulate glucose homeostasis in animal models of T2D, the role of CRF2, the only known cognate receptor for both UCN2 and UCN3 in the pathogenesis of T2D remains uncharacterized...Additionally, the expression of Pdx-1 and Glut2 was increased in Crhr2-/- islets compared with wild type. Our findings will help elucidate how dysregulated stress receptor function impairs glucagon and insulin secretion, ultimately contributing to the development of metabolic syndrome and diabetes."

Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • KEAP1 • PDX1

Impaired CRF2R Expression and Signaling Pathways in Adipocytes from an Insulin-Resistance Metabolic Syndrome Model (ENDO 2026) - "In conclusion, the CRF2R/Ucn2 system regulates the lipolytic pathway in adipocytes; however, in insulin-resistant MetS adipocytes, this signaling pathway is downregulated. Impaired function of this signaling pathway is directly linked to lipid metabolism and has a strong impact on the pathophysiology of metabolic syndrome, particularly in adipose tissue, suggesting its potential as a promising therapeutic agent."

Cardiovascular • Diabetes • Dyslipidemia • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • AKT2 • IR

A fusion-based multiomics classification approach for enhanced gene discovery in non-small cell lung cancer. (PubMed, Bioinform Adv) - "For the first time, ABCF3, ACAP2, LSG1, TBCCD1, UCN2, WDR53, ZNF639 and FYTTD1 appeared in the context of NSCLC. In conclusion, the integration of multiple omics types showed potential to deliver a more concise selection of NSCLC-relevant genes that could be clinically targeted in future. Data and source code are available on: https://github.com/kountaydwivedi/multiomics_fusion.git."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Characterization of the corticotropin-releasing hormone family in largemouth bass and their expression profiles in response to feeding and acute and chronic heat stress. (PubMed, J Fish Biol) - "Conversely, the downregulation of ucn2 under these conditions aligns with a potential orexigenic function. This study provides insights for future breeding of heat-tolerant varieties of largemouth bass."

Journal

A key to the Sabdariffa scotellii (Baker f.) Mwachala & R.L.Barrett group (Malvaceae, Hibisceae) in West Africa with descriptions of two new, threatened species from bowal habitats in the Republic of Guinea. (PubMed, PhytoKeys) - "Both species are assessed as Critically Endangered using the IUCN 2012 standard. We also discuss other recently described endemics of sandstone habitats in Guinea."

Journal

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