- |||||||||| Vampex (carbenoxolone gel) / York Pharma
Journal: Trojan-Horse Strategy Targeting the Gut-Liver Axis Modulates Gut Microbiome and Reshapes Microenvironment for Orthotopic Hepatocellular Carcinoma Therapy. (Pubmed Central) - Oct 7, 2024
Herein, a Trojan-horse strategy is proposed using an oral dextran-carbenoxolone (DEX-CBX) conjugate, which combines prebiotic and glycyrrhetinic acid (GA) homologs, to targeted delivery GA to HCC through the gut-liver axis for simultaneous modulation of hepatic inflammation and gut microbiota...Furthermore, DEX-CBX significantly increased natural killer T cells (5.7-fold) and CD8+ T cells (3.9-fold) as well as decreased M2 macrophages (59% reduction) over PBS treatment, resulting in a tumor suppression rate of 85.4%. DEX-CBX is anticipated to offer a novel strategy to precisely modulate hepatic inflammation and the gut microbiota to address both the symptoms and root causes of LPS-induced immunosuppression in HCC.
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Journal: Adenosine triphosphate release inhibitors targeting pannexin1 improve recovery after spinal cord injury. (Pubmed Central) - Oct 2, 2024
Furthermore, Brilliant Blue FCF administration reduced local astrocytic and microglial activation and neutrophil infiltration, and no differences in these histological effects were observed between compounds. Thus, Brilliant Blue FCF protects spinal cord neurons after spinal cord injury and suppresses local inflammatory responses as well as Brilliant Blue G and carbenoxolone.
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Journal: Ca2+ permeation through C-terminal cleaved, but not full-length human Pannexin1 hemichannels, mediates cell death. (Pubmed Central) - Jun 11, 2024
Moreover, cell death was prevented with carbenoxolone or 10Panx1 in ?371hPanx1 cells, whereas it was undetectable in HeLa Panx1-/- cells...In comparison, zVAD-FMK, a pancaspase inhibitor, reduced death by ~60%, suggesting the involvement of apoptosis. Therefore, alkaline pH increases the activity of ?371hPanx1HCs, leading to a critical intracellular free-Ca2+ overload that promotes cell death.
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Journal: Mechanisms of glioblastoma replication: Ca2+ flares and Cl- currents. (Pubmed Central) - May 31, 2024
These results describe the central role of Ca2+ flares and Cl- fluxes during mitosis and show that inhibition of Ca2+-activated Cl- channels blocks GBM replication, opening the way to new approaches for the clinical treatment of GBM. Implications: Our work identifies ionic fluxes occurring during cell division as targets for devising novel therapies for the glioblastoma treatment.
- |||||||||| Vampex (carbenoxolone gel) / York Pharma
Journal: Phosphorylation-dependent allosteric regulation of Cx43 gap junction inhibitor potency. (Pubmed Central) - Apr 30, 2024
The identified new phenomenon was Cx isoform-, inhibitor-, and cell type-dependent. Overall, these results suggest that compounds, the potency of which depends on receptor phosphorylation, might be of particular interest in developing targeted therapies for diseases accompanied by high kinase activity, such as cardiac arrhythmias, epilepsy, stroke, essential tremor, inflammation, and cancer.
- |||||||||| Vampex (carbenoxolone gel) / York Pharma
Journal: Astrocytic Regulation of Endocannabinoid-Dependent Synaptic Plasticity in the Dorsolateral Striatum. (Pubmed Central) - Jan 15, 2024
While pretreatment with the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonopentanoic acid (APV) failed to prevent synaptic depression induced by FC, it blocked the facilitation of HFS-LTD. While the lack of tools to disentangle astrocytes from neurons is a major limitation of this study, our data collectively support a role for astrocytes in modulating basal neurotransmission and eCB-mediated synaptic plasticity.
- |||||||||| Vampex (carbenoxolone gel) / York Pharma
Journal, IO biomarker, Immunomodulating, Stroma: Cellular interactions in cell sheets enhance mesenchymal stromal cell immunomodulatory properties. (Pubmed Central) - Nov 17, 2023
Beyond producing directly transferable multi-cellular hcBMSC constructs, cell sheet technology amplifies hcBMSC expression of immunomodulatory factors important to therapeutic action. Additionally, this work demonstrates the importance of cell-cell interactions as a tissue engineering design criterion to enhance consistent MSC functions.
- |||||||||| Vampex (carbenoxolone gel) / York Pharma
Persistent Prothrombotic Activation of Platelet Pannexin 1 Channels in Antiphospholipid Syndrome (Poster Hall; in person) - Sep 23, 2023 - Abstract #ACRConvergence2023ACR_Convergence_2241;
The accumulation of extracellular ATP promotes even further ATP release (and likely platelet activation) via P2Y12 and P2X7 receptors. PANX1 channel blockers such as CBX and PRB could be novel ways to restore platelet homeostasis in APS, potentially restraining thrombosis without a major impact on hemostasis ( Figure 1 ).
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Journal: Novel antidepressant mechanism of hypericin: Role of connexin 43-based gap junctions. (Pubmed Central) - Sep 21, 2023
Suppression of gap junctions by bilateral injection of carbenoxolone (CBX) in the prefrontal cortex of rats significantly inhibited the restoration of gap junctional dysfunction in depression by hypericin...Comparatively, CBX inhibited the remission of hypericin on gap junctional intercellular communication function. Gap junctional function might be a novel therapeutic target for hypericin in the treatment of depression and provide potential novel insights into the antidepressant mechanism of other herbal ingredients.
- |||||||||| Vampex (carbenoxolone gel) / York Pharma
Preclinical, Journal: Blocking Pannexin-1 Channels Alleviates Thalamic Hemorrhage-Induced Pain and Inflammatory Depolarization of Microglia in Mice. (Pubmed Central) - Jul 21, 2023
We found that TH led to microglial pannexin (Panx)-1, a large-pore ion channel, opening within the thalamus accompanied with thalamic tissue injury, pain sensitivities, and neurological deficit, which were significantly prevented by either intraperitoneal injection of the Panx1 blocker carbenoxolone or intracerebroventricular perfusion of the inhibitory mimetic peptide 10Panx...In summary, we conclude that blocking of microglial Panx1 channels alleviates CPSP and neurological deficit through, at least in part, reducing neural damage mediated by the inflammatory response of thalamic microglia after TH. Targeting Panx1 might be a potential strategy in the treatment of CPSP.
- |||||||||| Vampex (carbenoxolone gel) / York Pharma
Preclinical, Journal: Ca Dynamics of Gap Junction Coupled and Uncoupled Deiters' Cells in the Organ of Corti in Hearing BALB/c Mice. (Pubmed Central) - Jul 18, 2023
We have compared the ATP-evoked Ca transients and the effect of two different gap junction (GJ) blockers (octanol and carbenoxolone, CBX) on the Ca transients in DCs located in the apical and middle turns of the hemicochlea preparation of BALB/c mice (P14-19)...The cochlear turn-dependent effect of CBX might be the result of the differing connexin isoform composition of GJs along the tonotopic axis. The contribution of IP-mediated Ca signalling inhibition by CBX cannot be excluded.
- |||||||||| Vampex (carbenoxolone gel) / York Pharma
Journal: SARS-CoV-2 E and 3a Proteins Are Inducers of Pannexin Currents. (Pubmed Central) - Jun 14, 2023
This suggests distinct pathways for the induction of these cellular events by the two proteins. We conclude that SARS-CoV-2 E and 3a proteins are not viroporins expressed at the plasma membrane.
- |||||||||| Pandel (hydrocortisone probutate) / Novartis, Vampex (carbenoxolone gel) / York Pharma
Journal: Discovery of novel inhibitor of 11 beta-hydroxysteroid dehydrogenase type 1 using in silico structure-based screening approach for the treatment of type 2 diabetes. (Pubmed Central) - May 31, 2023
The binding energies of hydrocortisone succinate, medroxyprogesterone acetate, testolactone, hydrocortisone cypionate, deoxycorticosterone acetate, and hydrocortisone probutate were lower than that of substrate corticosterone...The docking study revealed that hydrocortisone cypionate has a higher binding affinity than carbenoxolone and its other analogs...These findings indicate the potential use of this FDA approved drug in the treatment of type 2 diabetes. However, validation by in vitro inhibitory studies and clinical trials on type 2 diabetes patients is essential to confirm the current findings.
- |||||||||| fluoxetine / Generic mfg.
Journal: Gap junction is essential for the antidepressant effects of fluoxetine. (Pubmed Central) - Apr 18, 2023
The compound 3h (2-(cyclopentylamino)-1-thia-3-azaspiro[4.5]dec-2-en-4-one) showed the strongest 11?-HSD1 inhibitory effect (IC = 0.07 Our study suggested that gap junction dysfunction blocks antidepressant effects of fluoxetine, contributing to understanding the mechanism underlying the time lag of fluoxetine.
- |||||||||| Vampex (carbenoxolone gel) / York Pharma
Journal: Carbenoxolone disodium suppresses the migration of gastric cancer by targeting HDAC6. (Pubmed Central) - Mar 28, 2023
Our study suggested that gap junction dysfunction blocks antidepressant effects of fluoxetine, contributing to understanding the mechanism underlying the time lag of fluoxetine. Cell viability, wound healing and transwell assays as well as animal studies have
- |||||||||| Journal: Screening of pharmaceutical and personal care products (PPCPs) along wastewater treatment system equipped with root zone treatment: A potential model for domestic waste leachate management. (Pubmed Central) - Mar 14, 2023
In general, carbamazepine, ibuprofen, acetaminophen, trimethoprim, sulfamethoxazole, caffeine, triclocarban, and triclosan are often reported in wastewater systems...In essence, RZT-based WWTP was found to be effective in removing the PPCPs and other organic contaminants in the study but results in stress the need for further comprehensive research on RZT system to conclude the exact removal efficacy and fate of PPCPs during treatment in the system. As a current research gap, the study also recommended RZT to be appraised for PPCPs in-situ remediation from landfill leachates, an underestimated source of PPCPs intrusion in the environment.
- |||||||||| probenecid / Generic mfg.
Journal: Probenecid affects muscle Ca2+ homeostasis and contraction independently from pannexin channel block. (Pubmed Central) - Feb 23, 2023
Since probenecid has been used both in the clinic and as a masking agent for doping in sports, these results should encourage evaluation of possible effects on muscle function in treated individuals. In addition, they also raise the question of whether probenecid-induced altered Ca2+ homeostasis may be shared by other tissues.
- |||||||||| Vampex (carbenoxolone gel) / York Pharma
Journal: Understanding the Role of ATP Release through Connexins Hemichannels during Neurulation. (Pubmed Central) - Feb 12, 2023
We propose two possible and highly conserved binding sites (N and E) in Cx46 that may mediate the pharmacological effect of CBX and ENX on the formation of NTDs. In summary, our results highlight the importance of ATP release mediated by HCs-Cxs during neurulation.
- |||||||||| Piqray (alpelisib) / Novartis, Vampex (carbenoxolone gel) / York Pharma
Review, Journal: Targeting PI3K/AKT signaling pathway in obesity. (Pubmed Central) - Jan 14, 2023
In this paper the druggability of PI3K as a target for compounds with anti-obesity potential is evaluated. Perspectives on the strategies and limitations for clinical implementation of obesity management using natural compounds modulating the PI3K/AKT pathway are suggested.
- |||||||||| Vampex (carbenoxolone gel) / York Pharma
Review, Journal: Pannexin1 channels-a potential therapeutic target in inflammation. (Pubmed Central) - Nov 29, 2022
Selective inhibition of Panx1 channels may not only limit acute inflammatory responses but may also prove useful in chronic inflammatory diseases, thereby improving human health. Here, we reviewed the current knowledge on the role of Panx1 in the initiation and resolution of the inflammatory response, we summarized the effects of Panx1 inhibition in inflammatory pathologies and recapitulate current Panx1 channel pharmacology with an outlook towards future approaches.
- |||||||||| Vampex (carbenoxolone gel) / York Pharma
Journal: Astroglial Connexins Inactivation Increases Relapse of Depressive-like Phenotype after Antidepressant Withdrawal. (Pubmed Central) - Nov 16, 2022
Interestingly, the combination of VENLA and CBX is also associated with a higher rate of relapse after treatment withdrawal. To our knowledge, this study is one of the first to develop a model of relapse, and our results reveal that Cx-mediated dynamic neuroglial interactions play a critical role in the efficacy of monoaminergic antidepressant drugs, thus providing new targets for the treatment of depression.
- |||||||||| Vampex (carbenoxolone gel) / York Pharma
Preclinical, Journal: Hyposmotic stress causes ATP release in a discrete zone within the outer cortex of rat lens. (Pubmed Central) - Oct 27, 2022
This seems to be mediated via the opening of pannexin channels in a specific zone of the outer cortex of the lens. Our results support the growing evidence that the lens actively regulates its volume and therefore, its optical properties, via puerinergic signaling pathways.
- |||||||||| Vampex (carbenoxolone gel) / York Pharma
Review, Journal: Anoikis-Associated Lung Cancer Metastasis: Mechanisms and Therapies. (Pubmed Central) - Oct 15, 2022
These products include artonin E, imperatorin, oroxylin A, lupalbigenin, sulforaphane, renieramycin M, avicequinone B, and carbenoxolone. This review summarizes the current understanding of the molecular mechanisms of anoikis regulation and relevant regulators involved in lung cancer metastasis and discusses the therapeutic potential of targeting anoikis in the treatment of lung cancer metastasis.
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Journal: Inhibition of Schwann cell pannexin 1 attenuates neuropathic pain through the suppression of inflammatory responses. (Pubmed Central) - Oct 12, 2022
This review summarizes the current understanding of the molecular mechanisms of anoikis regulation and relevant regulators involved in lung cancer metastasis and discusses the therapeutic potential of targeting anoikis in the treatment of lung cancer metastasis. In this study, we found that CCI-related neuroinflammation correlates with Panx 1 activation in Schwann cells, indicating that inhibition of Panx 1 channels in Schwann cells reduces neuropathic pain through the suppression of neuroinflammatory responses.
- |||||||||| Vampex (carbenoxolone gel) / York Pharma
Biomarker, Journal: Exploration of Biomarkers of Psoriasis through Combined Multiomics Analysis. (Pubmed Central) - Oct 11, 2022
The abnormal expression of GJB2 might play a critical role in psoriasis development and progression. The genes identified in our study might serve as a diagnostic indicator and therapeutic target in psoriasis.
- |||||||||| Vampex (carbenoxolone gel) / York Pharma
Preclinical, Journal: Gap junctions regulate the activity of AgRP neurons and diet-induced obesity in male mice. (Pubmed Central) - Sep 20, 2022
Using whole-cell patch-clamp recordings, we showed that pharmacological blockade of gap junctions induced hyperpolarization and decreased the frequency of action potentials in 50-70% of agouti-related protein (AgRP)-expressing neurons, depending on the blocker used (carbenoxolone disodium, TAT-Gap19 or Gap 26)...However, AgRPΔCX43 male, but not female mice exhibited a partial protection against high-fat diet-induced obesity, even though no significant changes in energy intake or expenditure were detected. In summary, our findings indicate that gap junctions regulate the activity of AgRP neurons, and AgRP-specific CX43 ablation is sufficient to mildly prevent diet-induced obesity specifically in males.
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