Vampex (carbenoxolone gel) / York Pharmaceuticals - LARVOL DELTA

Prenatal lipopolysaccharide exposure programs cardiac fibrosis via dysregulating of connexin 43 in offspring rats. (PubMed, Mol Med Rep) - "Cotreatment with the Cx43 gap junction inhibitor carbenoxolone (400 µM) and LPS further suppressed Cx43, LC3 and DNMT1 expression. However, cotreatment with the Cx43 agonist all‑trans retinoic acid (10 µM) attenuated LPS‑induced DNMT1 upregulation and LC3‑II/I ratio suppression. These findings demonstrate that the functional state of Cx43 critically links fetal inflammatory insults to postnatal cardiac fibrogenesis by dynamically regulating interconnected autophagy and DNA methylation, establishing Cx43 as an upstream regulatory node in this pathogenic network."

Journal • Preclinical • Fibrosis • Immunology • Inflammation • DNMT1

Random forest-based QSAR and molecular dynamics insights into steroidal pregnanes as 11β-hydroxysteroid dehydrogenase type 1 modulators for type 2 diabetes. (PubMed, Comput Biol Chem) - "While the reference carbenoxolone primarily involved peripheral polar contacts to stabilize its orientation, the pregnane scaffolds demonstrated deeper insertion into the hydrophobic catalytic cavity of 11β-HSD1, resulting in enhanced shape complementarity and van der Waals packing...Additionally, the leads exhibited favorable physicochemical and pharmacokinetic profiles. Overall, our findings provide mechanistic insights into ligand binding and highlight key structural features that may account for 11β-HSD1 modulation by steroidal pregnanes, offering a framework for the rational design of pregnane-derived therapeutics."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Regulation of the Angiogenic Potential of Endothelial Cells In Vitro under Conditions of Acute Hypoxic Stress: The Role of Homotypic Communication via Gap Junctions. (PubMed, Bull Exp Biol Med) - "Carbenoxolone, a specific GJ inhibitor, was used to suppress connexin-mediated signaling...Hypoxia moderately increased the proportion of necrotic cells without substantially influencing overall viability, whereas GJ blockade reduced necrosis, possibly due to disruption of intercellular transmission of death signals. These findings indicate a critical role of functionally active GJ in mediating the hypoxia-induced angiogenic response of endothelial cells, including modulation of key gene expression, migration, and capillary-like structure formation in vitro."

Journal • Preclinical • GJA1 • HIF1A

Tumor‑associated glucocorticoid inhibition by mifepristone reduces polymorphonuclear myeloid‑derived suppressor cells and promotes antitumor immunity in triple‑negative breast cancer‑bearing mice. (PubMed, Oncol Rep) - "Furthermore, treatment with carbenoxolone (a non‑selective 11β‑HSD1 inhibitor) in tumor‑bearing mice decreased plasma corticosterone levels, suppressed tumor growth and produced immune changes similar to mifepristone treatment. Mifepristone may restore antitumor immunity, likely by reducing PMN‑MDSCs through systemic corticosterone blockade. These insights could inform the development of novel therapeutic approaches for TNBC."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Transplantation • Triple Negative Breast Cancer

A comparative in vitro analysis of pannexin1-targeting agents. (PubMed, Biochem Pharmacol) - "Thus, carbenoxolone, probenecid, 10Panx1 and pannexin1-targeting nanobodies achieved blocking effects by reducing both ATP release and YO-PRO1 uptake. Collectively, the nanobodies show inhibitory effects by using smaller concentrations than traditional pannexin1 channel inhibitors. Therefore, nanobodies offer unique features for the development of pannexin1 channel inhibitors as novel anti-inflammatory therapeutics."

Journal • Preclinical • Inflammation

Purinergic Receptor- and Metabotropic Glutamate Receptor 5-Mediated Interactions Between Satellite Glial Cells and Neurons in Rat Trigeminal Ganglia. (PubMed, Glia) - "No neuronal excitability changes were induced by BzATP in the presence of the selective P2X7-R antagonist A740003, the metabotropic glutamate receptor 5 (mGluR5) inhibitor MTEP, or the hemichannel inhibitor carbenoxolone...These results indicate that glutamate released from SGCs via hemichannels in a paracrine manner may alter the excitability of neighboring TG neurons. Following activation of SGCs, we analyzed the excitatory changes occurring in neurons using patch-clamp recording in intact TG preparations, and, for the first time, identified that glutamate released from SGCs activates mGluR5 on neurons, contributing to these excitatory changes."

Journal • Preclinical • Pain • Peripheral Neuropathic Pain

Carbenoxolone attenuates renal ischemia-reperfusion injury in rats by modulating inflammatory cytokines, oxidative stress markers, and apoptotic pathways. (PubMed, Wiad Lek) - " Carbenoxolone significantly reduces RIRI-induced kidney damage, demonstrating its potential as a therapeutic agent for renal ischemic injuries."

Journal • Preclinical • Cardiovascular • Inflammation • Renal Disease • Reperfusion Injury • CASP3 • FOXO3 • IL1B • KIM1 • TNFA

Perfluorooctanoic acid and perfluorooctane sulfonate promote osteoclastogenesis in vitro through the activation of hemichannels. (PubMed, Arch Toxicol) - "For mechanism exploration, the hemichannel inhibitor, carbenoxolone (CBX), was used to incubate the cells during PFAS exposure. According to the results of our experiments, the PFASs promoted osteoclastogenesis and enhanced the Cx43 expression and hemichannel activity. After the treatment of CBX, the promoted osteoclastogenesis was significantly down-regulated, indicating the critical role of hemichannels."

Journal • Preclinical • GJA1

Upregulation of Intracellular Calcium by Piezo1 Activation Mediates UTMD-Activated ATP Release by Rat Erythrocytes. (PubMed, Ultrasound Med Biol) - "Our findings suggest that UTMD enhances ATP release from RBCs via a synergistic mechanism: Piezo1-mediated Ca2+ influx as the primary pathway, and non-Piezo1 pathways (including sonoporation) as complements. UTMD-induced Ca2+ influx is dominated by Piezo1-independent mechanisms. Panx1 acts as a key downstream effector. Although our results show Panx1 inhibition reduces ATP release, direct evidence of Piezo1-Panx1 interaction remains to be established. Proteomic data suggest cytoskeletal remodeling may play a role in this process. This knowledge may contribute to the development of new therapeutic strategies for improving microcirculatory perfusion."

Journal • Preclinical

Prothrombotic Activation of Platelet Pannexin 1 Channels in Antiphospholipid Syndrome. (PubMed, Arthritis Rheumatol) - "PANX1 channels appear to be important mediators of platelet activation in APS. Agents that block PANX1 may restore platelet homeostasis and limit thrombosis without impairing hemostasis."

Journal • Cardiovascular • Genetic Disorders • Hematological Disorders • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • Thrombosis

The Role of Gap Junctions in MSC-EA.hy926 (An Endothelial Cell Model) Crosstalk Under Hypoxic Stress: Regulation of the Angiogenic Response. (PubMed, Int J Mol Sci) - "In a cell co-culture model at 0.1% O2 using a specific GJ inhibitor (carbenoxolone), molecular, cellular, and functional tests were performed: assessment of viability, proliferation, migration, secretion of angiogenic mediators, and expression of crucial genes. GJ blockade was accompanied by decreases in the proliferation and migration activity and angiogenic potential of the conditioned medium in in vitro and in ovo tests. These data highlight the importance of the GJ in coordinating the angiogenic response in conditions of acute hypoxia and can be used to develop protocols for regenerative medicine."

Journal

Gap Junctional Versus Paracrine Signaling in the Human Lens Epithelium: Analysis Based on Multicellular Ca²⁺ Imaging and Computational Modeling. (PubMed, Invest Ophthalmol Vis Sci) - "Mechanically induced Ca²⁺ waves were recorded, and the contribution of specific signaling pathways was evaluated by pharmacological intervention using apyrase (an ATP-hydrolyzing enzyme) and carbenoxolone (CBX; a gap-junctional blocker)...Our results highlight the cooperative roles of gap-junctional and ATP-based paracrine signaling in mediating mechanically induced Ca²⁺ wave propagation in the human lens epithelium. This dual-pathway mechanism may be critical for coordinated cellular responses that support physiological processes such as ion homeostasis and transparency maintenance in the human lens."

Journal • Cataract • Ophthalmology

11β-HSD2-dependent Glucocorticoid Inactivation Is a Suppressor of Leptin Signaling In Vitro (OBESITY WEEK 2025) - " Both dexamethasone (synthetic glucocorticoid) and cortisol (natural glucocorticoid) enhanced leptin signaling...In line, carbenoxolone, a non-selective inhibitor of 11β-HSDs also enhanced, whereas overexpression of 11β-HSD2 attenuated leptin signaling... In conclusion, glucocorticoids enhance leptin sensitivity while its inactivation by 11β-HSD2 serves as a negative modulator of leptin signaling. The data highlight a novel but critical role of glucocorticoid and its intracellular conversion in leptin signaling in our in vitro model of leptin sensitivity."

Preclinical • Genetic Disorders • Obesity • LEP • LEPR

FGF13 Regulates VGSC-Independent Cardiomyocyte Impulse Propagation via Cx43 Trafficking. (PubMed, Circ Res) - "Carbenoxolone, a Cx43 gap junction uncoupler, markedly prolonged the QRS duration, leading to conduction system block in cFgf13KO but not in wild-type mice...FGF13 ablation destabilized microtubules and reduced the expression of tubulins and MAP4, the major cardiac microtubule regulator. FGF13 regulates microtubule-dependent trafficking and targeting of Cx43 and impacts cardiac impulse propagation via VGSC-independent mechanisms."

Journal • Atrial Fibrillation • Cardiovascular

ATP release and metabolism by human and guinea pig airways and P2X receptor-dependent effects on bronchopulmonary vagal afferent nerve subtypes. (PubMed, Br J Pharmacol) - "These results predict a desirable safety profile for P2X receptor blockade and identify multiple potential biomarkers that may differentiate responders from non-responders in studies evaluating P2X blockers in chronic cough patients."

Journal • Anesthesia • Asthma • Chronic Cough • Cough • Immunology • Pulmonary Disease • Respiratory Diseases

Contractions of ex-vivo mouse bladder driven by activation of channelrhodopsin-2 expressed in urothelial cells. (PubMed, Sci Rep) - "Nifedipine, which blocks extracellular Ca2+ entry, abolished the contractions...Hemichannel inhibitor carbenoxolone disodium and the exocytotic pathway of transmitter release inhibitor brefeldin A also showed significant inhibition of the contractions. In conclusion, we validated the previous hypothesis that urothelial release factors can influence bladder contractions locally without the need for signaling from the central nervous system. Further studies are needed to determine the relevance of this signaling pathway in normal bladder physiology and pathophysiologic conditions."

Journal • Preclinical

Solvated forms of carbenoxolone - different degrees of structural similarities. (PubMed, Acta Crystallogr B Struct Sci Cryst Eng Mater) - "Ribbons and layers, recurring building motifs in these structures, are primarily based on dispersion interactions. The degree of similarity (1D, 2D or 3D) between these new structures and four CBXH2 structures from the Cambridge Structural Database was evaluated using geometrical parameters and XPac calculations."

Journal

Analgesic and anti-inflammatory properties of carbenoxolone: a review. (PubMed, Inflammopharmacology) - "Noteworthy, side effects of CBX include sodium retention, weight gain, electrolyte imbalances, hypokalemia, mild edema, elevated blood pressure, headache, and heartburn. Given the strong preclinical evidence but limited clinical validation, further research is needed to clarify CBX analgesic/anti-inflammatory mechanisms/efficacy and fully elucidate its safety profile."

Journal • Review • Gastroenterology • Immunology • Neuralgia • Oncology • Pain • Peptic Ulcer • IL6 • NLRP3 • TNFA

New Derivatives of 2-(Cyclohexylamino)thiazol-4(5H)-one as Strong Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1: Synthesis, Antiproliferative and Redox-Modulating Activity. (PubMed, Int J Mol Sci) - "The most active compound, 3h with IC50 = 0.04 µM, became a more potent and selective inhibitor than carbenoxolone...This study showed an increase in ROS levels for SK-MEL-30, Caco-2, and MDA-MB-231 lines, while in the case of GSH levels, its reduction was observed in most experimental sets. The presented data suggest that the tested compounds are promising therapeutic agents with dual action because they offer the possibility of simultaneous regulation of metabolic disorders by inhibiting 11β-HSD1 and play a key role in anticancer therapy, which makes them prospective candidates for further clinical studies."

Journal • Brain Cancer • Breast Cancer • Colon Cancer • Colorectal Cancer • Glioma • Melanoma • Metabolic Disorders • Oncology • Pancreatic Cancer • Solid Tumor

The hydroalcoholic extract of the leaves of red mombin (Spondias purpurea L.) is more effective in accelerating ulcer healing than preventing them in rodents. (PubMed, Inflammopharmacology) - "The gastroprotection was assessed using acidified ethanol-induced gastric ulcer in mice given orally with the vehicle, carbenoxolone (200 mg/kg), or SPHE (10-1.000 mg/kg). The extract's healing activity was evaluated using acetic acid-induced ulcers in rats treated with vehicle, omeprazole (20 mg/kg), or SPHE (3-300 mg/kg)...SPHE induced gastroprotection at a dose of 1.000 mg/kg, and this effect was lost in mice treated with NEM, indomethacin, or yohimbine but not L-NAME...The presence of hibiscus acid, hydroxy citric acid, hibiscus acid glycoside, ellagic acid, and the flavonoids quercetin and rutin were confirmed and quercetin, caffeic acid, p-coumaric acid, gallic acid, and epigallocatechin were quantified. Therefore, SPHE accumulated chemicals with higher gastric healing potential mediated by gastric protective features, specifically antioxidant resources, mucus barrier, and cell proliferation."

Journal • Preclinical • Peptic Ulcer

Dioscin initiates dual roles in bladder cancer progression via miR-195-5p/FASN/SLC3A2 axis-mediated cell death mechanisms. (PubMed, Transl Oncol) - "Notably, dioscin potentiated cisplatin's antitumor efficacy against both BIU87 and cisplatin-resistant BIU87 bladder cancer cells at low micromolar concentrations. Intriguingly, the bladder cancer cell induced by dioscin could be counteracted by inhibitors of apoptosis, necroptosis, and ferroptosis, particularly in the presence of gap junction inhibitor carbenoxolone...Crucially, dioscin exhibited cytotoxicity against normal urothelial (SV-HUC-1) and renal (MDCK) cells, warranting cautious therapeutic application. These findings unveil a novel miR-195-5p/FASN/SLC3A2 axis through which dioscin initiates bladder cancer cell death, while highlighting dual roles of dioscin in bladder cancer and the necessity for dosage optimization to balance its antitumor potency and off-target toxicity."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • FASN • MIR195 • SLC3A2

Regulation of food intake by Connexin43 via adipocyte-sensory neuron electrical synapses. (PubMed, Mol Metab) - "Gap junction-mediated electrical communication between adipocytes and sensory neurons may regulate feeding."

Journal • ADIPOQ • GDF15 • GJA1

Pannexin channels in inflammation and tumorigenesis. (PubMed, Front Cell Dev Biol) - "Current pharmacological inhibitors of Panx channels include Food and Drug Administration (FDA)-approved drugs such as Carbenoxolone (CBX), Probenecid (PBN), and Spironolactone, along with chemically synthetic compounds 10Panx. Both genetic modulation of Panx expression and pharmacological manipulation have demonstrated the channels' critical involvement in various human pathologies, establishing them as promising therapeutic targets for clinical intervention. In this review, we will specifically examine the signaling regulatory functions of Panx channels in the processes of inflammation and tumorigenesis; systematically evaluate the therapeutic potential of Panx inhibitors in these pathological contexts, critically analyze current research limitations, and strategically propose future perspectives in Panx channels and its inhibitors research."

Journal • Review • Immunology • Oncology

A Decoy Oligodeoxynucleotides Disturbing Forkhead Box O3 Mediated ctnna2 Transcriptional Repression Prevents Postoperative Neurocognitive Disorder in Mice. (PubMed, CNS Neurosci Ther) - "These results provided a new revenue for identifying targets and developing interventions for PND. The decoy, due to its specificity and short acting time, merits further exploration for possible clinical use."

Journal • Preclinical • CNS Disorders • Cognitive Disorders • Developmental Disorders • ASCL1 • FOXO3 • TNFA

Mechanism of shear stress-induced ATP release in ventricular myocytes: roles of pannexin and mitochondria. (PubMed, Am J Physiol Cell Physiol) - "Shear-induced ATP release was suppressed by probenecid, low concentrations of carbenoxolone, or the pannexin (Panx) 1 inhibitory peptide 10Panx1 by 60-75%, suggesting a major role for Panx. Pharmacological screening further revealed a partial (30-40%) role of 9-anthracenecarboxylic acid-sensitive, tamoxifen-insensitive Cl- channels in ATP release...This shear response was suppressed by mitochondrial uncoupling or inhibition of the electron transport chain by 70-80% but was rather enhanced by Mito-TEMPO. Our data suggest that shear stress induces ATP release from murine ventricle cells mainly via Panx and that mitochondrial oxidative phosphorylation may be required for this response."

Journal