Vampex (carbenoxolone gel) / York Pharmaceuticals - LARVOL DELTA

Differences in analytical approach during conduction velocity analysis of optically mapped hearts affect reported data and conclusions. (PubMed, Comput Methods Programs Biomed) - "Vector inclusion parameters substantially influence reported conduction velocity and anisotropy, and can alter statistical conclusions. A constraint-based, parsimonious approach to parameter selection improves robustness and transparency without invoking optimization, providing a framework adaptable to other analytical workflows lacking ground truth."

Journal • Cardiovascular

Eimeria bovis-infected host cell-bystander cell interactions are essential for effective macromeront formation. (PubMed, Front Cell Infect Microbiol) - "The functional relevance of connexins was supported by blocking gap junction formation in BCs with carbenoxolone or Gap26 (inhibits Cx37, Cx40 and Cx43), both of which impaired parasite development...Moreover, inhibitor-based impairment of BC metabolism demonstrated that intact glycolytic and glutaminolytic activities in addition to functional cholesterol esterification and trafficking are required in BCs to sustain effective merozoite I production in BC-MCHC-cultures. Collectively, the current findings support the hypothesis that effective intracellular E. bovis macromeront formation depends on an environmental BC-based support network involving BC metabolic integrity, short-range gap-junctional small molecule transfer, and long-range TNT-mediated mitochondria donation."

Journal • Developmental Disorders • Infectious Disease • Metabolic Disorders

PCB2 improves porcine oocyte maturation by enhancing TZP-mediated cumulus-oocyte communication. (PubMed, Theriogenology) - "Furthermore, we discovered that gap junctional uncoupler carbenoxolone (CBX) treatment impaired oocyte maturation (P < 0.05), cumulus expansion (P < 0.05), oocyte viability (P < 0.001), and lipid content (P < 0.001), whereas PCB2 partially rescued these defects (P < 0.05). Collectively, these findings demonstrate that PCB2 improves porcine oocyte maturation through the combined interaction between improved redox homeostasis, enhanced cumulus cell function, cellular metabolism, and cumulus-oocyte communication."

Journal • Preclinical

Bioinspired Quinoline-2 Derivatives Based on the Natural Alkaloid 2-Phenylquinoline from Conchocarpus longifolius (A.St.-Hil.) Kallunki & Pirani: Pharmacological Evaluation of Their Gastroprotective Potential. (PubMed, Molecules) - "Carbenoxolone (200 mg/kg, p.o., positive control) inhibited gastric lesion formation by 94.1%...These findings suggest that its gastroprotective effects are mediated by antioxidant and anti-inflammatory mechanisms, identifying compound 4 as the most promising candidate for the prevention and treatment of peptic ulcers. Its promising pharmacological profile warrants further investigation to elucidate its molecular mechanisms of action, assess its safety and efficacy in additional preclinical studies, and explore its potential for future therapeutic development."

Journal • Gastroenterology • Oncology • Peptic Ulcer • TNFA

Fumarate-associated immunometabolic network in Periodontitis revealed by integrated transcriptomic and single-cell RNA sequencing analysis. (PubMed, PLoS One) - "In addition, computational drug screening and molecular docking highlighted carbenoxolone and a CXCR4 antagonist (USL311) as potential candidates for future study. Overall, this study provides an integrative view of fumarate-associated immunometabolic alterations in periodontitis and identifies candidate transcriptomic markers and therapeutic hypotheses that warrant further experimental validation."

Journal • Dental Disorders • Inflammation • Periodontitis • MEF2C

Binding to Albumin and Off-Target Toxicity Confound the Use of LRRC8/VRAC Channel Blockers in Cell Physiology Assays. (PubMed, bioRxiv) - "In serum-containing media, structurally diverse VRAC blockers (DCPIB, DIDS, carbenoxolone, phloretin, and bromadiolone) reduced proliferation in a non-uniform manner, with potencies that did not correlate with reported VRAC affinities and varied markedly among cell lines...Under standard culture conditions, serum albumin masks much of their intrinsic cytotoxicity. These results underscore the need for rigorous molecular controls in pharmacological studies and provide basis for developing more selective and less toxic VRAC-targeting agents."

Journal • Brain Cancer • Cardiovascular • Glioblastoma • Metabolic Disorders • Myocardial Infarction • Oncology • Solid Tumor • LRRC8A

11β-HSD1-mediated cortisol conversion promotes immune suppression and tumor cell migration in canine mammary carcinoma. (PubMed, Res Vet Sci) - "CMC cell lines efficiently converted inactive cortisone to active cortisol, a process significantly inhibited by the non-selective 11β-HSD1 inhibitor carbenoxolone, demonstrating that they possess the capacity for 11β-HSD1-mediated cortisol conversion...Importantly, both immunosuppression and increased migration were reversed by the GC receptor antagonist mifepristone. These findings represent the first report of autonomous cortisol conversion in CMC, suggesting that tumor-derived GCs contribute to metastatic niche formation through immune evasion and enhanced motility. Our results identify the 11β-HSD1-GC axis as a potential novel therapeutic target for CMC."

Journal • Breast Cancer • Oncology • Solid Tumor • CD8

Gap junction communication regulates luminal-myoepithelial crosstalk and cell differentiation in a bilayered human mammary epithelial cell model. (PubMed, Biol Methods Protoc) - "Inhibition of gap junction communication by carbenoxolone disrupted these lineage-specific differentiation patterns. These findings highlight the importance of direct communication in regulating epithelial identity and underscore the LCS as a physiologically relevant model for studying mammary gland biology and external influences that can impact the epithelial differentiation."

Journal • CALD • KRT14 • KRT18 • KRT18

Mechanistic insights into DCPIB inhibition of VRAC: Electrostatic control and binding plasticity. (PubMed, J Gen Physiol) - "Mutations of R103 abolished ATP-dependent block of VRAC but did not affect inhibition by DCPIB or the related inhibitor carbenoxolone (CBX), indicating distinct binding mechanisms...Our findings reveal an adaptable binding mechanism for DCPIB, contrasting with described lipid-displacement mechanisms for other VRAC inhibitors, and establish electrostatic complementarity as the primary determinant of high-affinity block. These insights provide a framework for rational design of next-generation VRAC inhibitors with improved specificity."

Journal • LRRC8A

Inhibition of T Cell-Intrinsic Glucocorticoid Production Enhances Tumor Immunity (ENDO 2026) - "To examine whether immune cell 11β-HSD1 inhibits tumor immunity we then implanted mice with MC38 (colon carcinoma) or LLC (Lewis lung carcinoma) tumors, with minimal and no 11β-HSD1 activity, respectively, and administered vehicle or an 11β-HSD1 inhibitor (carbenoxolone or PF-915275, 50 mg/kg) daily...These findings indicate that T cell 11β-HSD1 regenerates active glucocorticoids that impair tumor immunity and promote tumor growth. Pharmacological inhibition of 11β-HSD1 may therefore be a useful immunotherapy for a wide range of tumors, independent of tumor cell 11β-HSD1 expression."

IO biomarker • Colon Cancer • Lung Cancer • Oncology • Solid Tumor

Connexin-43-Mediated Gap Junction Coupling Between Adipocytes Regulates Norepinephrine-Induced Ca2+ Responses in Perivascular Adipose Tissue. (PubMed, Cells) - "Blocking gap junction coupling with the drug carbenoxolone (Cbx) limited NE-evoked Ca2+ responses among adipocytes, while blocking Cx43 hemichannels with the mimetic peptide 43Gap26 had no significant effect...These observations support the conclusion that Cx43-mediated gap junction coupling among PVAT adipocytes contributes to distributing signals initiated by NE; however, how this mechanism contributes to regulating vessel constriction remains unclear. This, and how potential compensatory mechanisms are enacted in adipocytes lacking Cx43, should be addressed in future work."

Journal

Connexin Regulation and Modulation of Neural Stem Cell Differentiation Induced by Cell-Permeable Itaconate. (PubMed, J Cell Physiol) - "We found that dimethyl itaconate modulates Cxs expression in NSCs, increasing Cx36 levels, and promotes NSCs differentiation toward a neuronal phenotype, while inhibition of Cxs-based channels with carbenoxolone or mefloquine abolishes these dimethyl itaconate-induced effects. Collectively, these findings highlight a regulatory role for cell-permeable itaconate and contribute to the understanding of intercellular communication in the CNS microenvironment, providing insights into potential therapeutic strategies for CNS repair and regeneration."

Journal • Immunology • Inflammation

Impact of anti-peptic ulcer disease (PUD) medications on hyperlipidemia risk in patients with PUD: a population-based retrospective cohort study. (PubMed, Ther Adv Endocrinol Metab) - "The use of anti-PUD medications, such as H2 receptor antagonists, proton pump inhibitors, antibiotics, prostaglandin analogs, anticholinergics, antacids, and carbenoxolone, but not bismuth salts, was associated with a lower risk of developing hyperlipidemia than non-use. Patients with PUD were more likely to develop hyperlipidemia. However, patients receiving anti-PUD medications had a lower incidence of hyperlipidemia."

Journal • Retrospective data • Cardiovascular • Dyslipidemia • Gastroenterology • Gastrointestinal Disorder • Peptic Ulcer

Prodromal changes in cortical neuron physiology before amyloid pathology in a mild model of Alzheimer's disease. (PubMed, Sci Rep) - No abstract available

Journal • Alzheimer's Disease • CNS Disorders

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