Glucox Biotech AB as it stands
Vision – that Glucox Biotech AB (GB) have a strong pipeline with NADPH oxidase inhibitors that will be possible to develop into efficient and safe pharmaceuticals. The strongest GB candidate is a highly specific and selective NOX4 inhibitor.
Mission – to develop safe and effective pharmaceuticals. Also with these highly selective and specific NOX4 inhibitors aid the academic community to explore and understand physiologic function and pathologic impact in disease driving environments.
The GB NOX4 inhibitors have lately been investigated to develop efficient treatment for:
- Harmful conditions related to prolonged hypoxia followed by reperfusion
- Ischemic stroke
- Acute Kidney Injury
- Conditions caused by prolonged and chronic hyperglycemia
- Protection of beta-cells in diabetic condition
- Protection of kidney in a diabetic condition
- Combination of both hypoxia and hyperglycemic conditions
- Diabetic retinopathy in a diabetic condition.
Among all the ongoing studies that GB presently are involved in together with academic groups – is presently the most promising therapeutic studies done to prevent the development of diabetic retinopathy. The first proof made in Rat diabetes models. These studies made with a provisional formulation. Now a new formulation has been developed by the CRO IRIS Pharma – an expert company in the area of eye disease. This new formulation is potentially suitable for treating humans and are presently being evaluated in Rabbit animal models.
Reducing Oxidative Stress at the Source
Glucox Biotech AB activity focuses on developing pharmaceutical treatments, targeting specific sources of reactive oxygen that causes oxidative stress in diabetes with its complications, based on the company’s proprietary rights covering the rights to develop pharmaceutical substances for treating disorders related to oxidative stress on the basis of reactive oxygen species produces by NAD(P)H-oxidase, primarily NOX4. Recent literature establishes NOX4 as an important factor also in stroke and heart infarction. Therefore, Glucox Biotech also develops NOX4 inhibitors for the treatment of these conditions.
The idea behind Glucox Biotech’s therapies is to reduce oxidative stress by preventing the intracellular formation of reactive oxygen species and thus improve blood glycemic control and also decrease the critical risks and delay progression of complications in type 2 patients as well as cellular damage in stroke and heart infarction.
Glucox Biotech owns several patents covering the exclusive rights to develop pharmaceutical substances for treating insulin resistance and diabetes on the basis of reducing reactive oxygen species produces by NAD(P)H-oxidase (NOX4).
As off today, Glucox Biotech (GB) collaborates with European academic groups in the following areas:
– Investigation of GB inhibitors in Diabetic Retinopathy
– Investigation of GB Nox4 inhibitors in fibros assay
– Investigation of GB NOX4 inhibitors in acute kidney injury (AKI)
– Investigation of GB Nox4 inhibitors in Marfans syndrome
– Investigation of GB Nox4 inhibitors in protection of beta-cells at diabetic conditions.
– Investigation of GB Nox4/Nox2 inhibitor in protection heart at ischemic stroke.
– Investigation of GB Nox4 inhibitor in ischemic stroke brain
– Investigation of Nox4 role in liver disease and cancer
News in brief
Pharmacologic treatment of Diabetic Retinopathy (DR)
2020/2023 A fruitful collaboration with Prof. Kyriaki Thermos have resulted in one initial publication using AMPA injection to induce glutamat toxicity in eye and the protection of GLX7013114 treatment to prevent neuronal damage (Dionysopoulou et al., 2020 in Exp. Eye Res.) and a second publication recently accepted in Diabetes journal that will be published soon. The aim of the two studies is to investigate the role of the highly selective NOX4 inhibitor, GLX7013114, in the early events of diabetic retinopathy (DR), using animals with diabetes induced oxidative stress, neurodegeneration, neuroinflammation and vascular leakage, and to evaluate its efficacy as a therapeutic treatment for this stage of DR.
Initial publication 2020: Stavroula Dionysopoulou, Per Wikström, Erik Walum, KyriakiThermos, Effect of NADPH oxidase inhibitors in an experimental retinal model of excitotoxicity Experimental Eye Research 200 (2020) 108232
The collaboration with The accepted publication Jan 2023 in Diabetes – will be posted when it is public.
Protecting beta-cells in diabetes using NOX4 inhibitors and clarify mechanisms in the mitochondria using GLX7013114 with its highly selective and specific NOX4 inhibition
A fruitful collaboration for several years with prof. Nils Welsh with colleagues at Uppsala university. Has rendered into several publications including a thesis demonstrating the power of GB toolbox of NOX inhibitors.
2022 The pathological significance of NOX4 activity were beautifully demonstrated at Uppsala University using GBs NOX4 inhibitors (GLX7013114, GLX351322 and GLX481372). Three of four publications was utilizing GB inhibitors as part of this thesis (Andris Elksnis, “Pharmaceutical Protection of Beta-Cells in Diabetes – Using Tyrosine Kinase Inhibition and NOX4 Inhibitors”) that was defended 3 June 2022, at Faculty of Medicine. It clearly demonstrate that stress induced NOX4 activity is detrimental to beta-cells mimicking a diabetic environment.
Highlighting two of the publications that demonstrate the power of having access to GBs highly selective and specific NOX4 inhibitors.
- In the paper “The novel NADPH oxidase 4 selective inhibitor GLX7013114 counteracts human islet cell death in vitro” Wang et al. PLOS ONE September 28 , 2018 – three different NOX4 inhibitors produced by GB was used as tool to investigate the role of NOX4 when human beta-cells were exposed to inflammatory cytokines as well as high glucose in combination of palmitate. It was concluded that Selective NOX4 inhibition significantly protected beta-cells against both cytokines and high-glucose + palmitate.
- In the paper “Pharmacological Inhibition of NOX4 Improves Mitochondrial Function and Survival in Human Beta-Cells”, Elksnis et al., Biomedicines 2021, 9, 1865 – it was demonstrated that NOX4 inhibition using GLX7013114 increased mitochondrial membrane potential, mitochondrial reactive oxygen species and ATP/ADP ratio in a human beta-cell line, and this was paralleled with protection against human islet cell death when challenged with high-glucose and palmitate.
NEW PUBLICATIONS SUPPORT THE ROLE OF NOX4 IN DIABETES:The important pathological role of Nox4 over-activity in diet induced obesity is further emphasized in a recent review publication (Roles of Reactive Oxygen Species on Insulin Resistance in Adipose Tissue, Han CY, Diabetes Metab J. 2016 Aug;40(4):272-9). In a previous publication by Glucox Biotech and Prof. Nils Welsh lab (Anvari et al., The novel NADPH oxidase 4 inhibitor GLX351322 counteracts glucose intolerance in high-fat diet-treated C57BL/6 mice, Free Radic Res. 2015;49(11):1308-18) it was proposed that pancreatic beta-cell dysfunction is promoted by oxidative stress caused by Nox4 over activity. Interestingly both publications describe the important primary function of Nox4 activity that in a prolonged energy excess (glucose and palmitate) results in activity promoting the pathology of diabetes type 2.
GLUCOX AT GORDON CONFERENCE: Glucox’ Head of Research, Per Wikström, was invited speaker attending a Gordon Conference, June 5-10, 2016, and presented the SAR development of the latest highly selective Glucox´ Nox4 inhibitors. Structure activity relationship (SAR) was determined using Nox4 membrane- and whole cell overexpressing Nox4-assay. Two of the most interesting Nox4 inhibitors that were presented have the following specification regarding selectivity towards other Nox iso forms: GLX7013114 with 0.3 microM (IC50 Nox4) and the selectivity 22 microM (IC50 Nox1) and for GLX7013107 with 2.4 microM (IC50 Nox4) and the selectivity 44 microM (IC50 Nox1). Both compound demonstrated more or less no inhibiting capability at all towards Nox2 and Nox5 as well as for Xanthine oxidase. No internal reducing capability could be determined.
GLUCOX´ CEO PRESENTED ON NOVEL COMPOUNDS: Erik Walum gave a presentation titled: ”Identification and characterization of novel small-molecule Nox inhibitors” at the 2nd Biotech Hanse Forum in Stockholm, June 6, 2016.
NEW PUBLICATION ON GLUCOX COMPOUND: E. Anvari, P. Wikström, E. Walum & N. Welsh; The novel NADPH oxidase inhibitor GLX351322 counteracts glucose intolerance in high-fat diet-treated C57BL/6 mice. Free Radical Research, 2015; Early on line: 1-11.
GLUCOX´ CEO PRESENTED ON NOVEL COMPOUND: Erik Walum gave a presentation titled : ”Use of in vitro methods in the development of a Nox4/Nox2-inhibitor (GLX481304) for the protection of oxidative stress” at the SSCT-Swetox Workshop: Mechanisms, markers and models – the 3M strategy in risk assessment, October 13 – 15, 2015, at Bommersvik, Järna.
GLUCOX´CEO PRESENTED IN MEETING ON OUTSOURCING: CEO Erik Walum presented a paper titled: ”Hit-to-lead compound development in a dynamic life science ecosystem” at the PharmaOutsourcing conference at Stockholm Waterfront, December 9, 2015.
EU-ROS – A COST ACTION: This action is one of the largest actions in the EU COST program. The action started with 26 European countries represented and has since been growing with other representatives invited from outside Europe. This organization exchange knowledge regarding research around specific sources of ROS that is linked to diseases such as diabetes and diabetic complications, neurodegenerative diseases (Alzheimer, Parkinson, Huntington, Amyotrophic lateral sclerosis, Schizophrenia), stroke and cancer. The action stimulates all kinds of collaborations such as academic as well as business deals. Glucox Biotech AB takes an active part sharing its Nox inhibitors for academic discovery and in return using this information for drug development into successful and safe pharmaceuticals.
Glucox’ Head of Research, Per Wikström, took part in the following EU-ROS meeting: April 21-24, 2015 in Munich, Germany and gave a presentation with the title: ”Identification and characterization of novel small-molecule Nox inhibitors”. Another EU-ROS meeting was held on October 22-24, 2015 in Bucharest, Romania.