- |||||||||| azemiglitazone (MSDC-0602K) / Cirius Therap, AZD-3965 / Cancer Research UK, mitoglitazone (MSDC-0160) / Metabolic Solutions
Journal: Glyceraldehyde-3-Phosphate Dehydrogenase/1,3-Bisphosphoglycerate-NADH as Key Determinants in Controlling Human Retinal Endothelial Cellular Functions: Insights from Glycolytic Screening. (Pubmed Central) - May 30, 2025 Pharmacological inhibitors targeting lower glycolytic components were tested: heptelidic acid for glyceraldehyde-3-phosphate dehydrogenase (GAPDH), NG-52 for phosphoglycerate kinase (PGK), shikonin for pyruvate kinase M (PKM), galloflavin for lactate dehydrogenase (LDH), AZD3965 for lactate transporter (MCT1), and MSDC-0160 for the mitochondrial pyruvate carrier (MPC)...GAPDH and its downstream products (1,3-BPG and NADH) are shown to play a pivotal role in maintaining barrier integrity and promoting HREC adhesion and spreading. These findings guide the development of targeted interventions that modulate HREC bioenergetics to treat endothelial dysfunction in various retinal disorders, while minimizing potential adverse effects on healthy endothelial cells.
- |||||||||| azemiglitazone (MSDC-0602K) / Cirius Therap, pioglitazone / Generic mfg., rosiglitazone / Generic mfg.
Journal: Uncovering mechanisms of thiazolidinediones on osteogenesis and adipogenesis using spatial fluxomics. (Pubmed Central) - Mar 16, 2025 These findings indicate that the new-generation drugs do not compromise bone structure, offering a safer alternative for treating insulin resistance. Moreover, these results highlight the ability of cell compartment-specific metabolite labeling by click reactions and tracer metabolomics analysis of complex lipids to discover molecular mechanisms within the intersection of carbohydrate and lipid metabolism.
- |||||||||| Potential for New Oral Insulin Sensitizers in Combination with GLP-1 Agonists (Poster Hall (West A4-B2); 892) - May 20, 2024 - Abstract #ADA2024ADA_2897;
MSDC-0602K (azemiglitazone) is a second-generation insulin sensitizer that was designed based on the knowledge of the activity of active metabolites of the first-generation insulin sensitizer pioglitazone...Here we have looked specifically at the 23 subjects with NASH (MASH) and type 2 diabetes who had been enrolled in the trial while on a stable dose of a GLP1 agonist (11 liraglutide, 8 dulaglutide, and 4 exenatide)...Some subjects who had been on a GLP1 continued to lose weight while others did not. Given the major effects of his pharmacology to improve insulin sensitivity Iin skeletal muscle and based on some existing precedent with high dose pioglitazone, maintenance of lean mass could be a component of the overall pharmacology achieved with oral metabolic modulators.
- |||||||||| azemiglitazone (MSDC-0602K) / Cirius Therap, Paxlovid (nirmatrelvir and ritonavir) / Pfizer
Journal: Inhibition of the mitochondrial pyruvate carrier simultaneously mitigates hyperinflammation and hyperglycemia in COVID-19. (Pubmed Central) - Apr 18, 2023 We further showed that MSDC enhanced responses to nirmatrelvir (the antiviral component of Paxlovid) to provide high levels of protection against severe host disease development following SARS-CoV-2 infection and suppressed cellular inflammation in human COVID-19 lung autopsies, demonstrating its translational potential for treating severe COVID-19. Collectively, we uncover a metabolic pathway that simultaneously modulates pulmonary inflammation, tissue recovery, and host metabolic health, presenting a synergistic therapeutic strategy to treat severe COVID-19, particularly in patients with underlying metabolic disease.
- |||||||||| azemiglitazone (MSDC-0602K) / Cirius Therap, Paxlovid (nirmatrelvir and ritonavir) / Pfizer
Inhibition of MPC Simultaneously Mitigates Hyperinflammation and Hyperglycemia in COVID-19 (Walter E. Washington Convention Center, Room 201 (Level 2)) - Mar 25, 2023 - Abstract #ATS2023ATS_2609; We have utilized murine models of influenza and SARS-CoV-2 infection to test whether MSDC-0602K (MSDC), a second-generation insulin sensitizer that targets mitochondrial pyruvate carrier (MPC), can simultaneously dampen pulmonary inflammation and hyperglycemia. Collectively, we uncover a metabolic pathway that simultaneously modulates pulmonary inflammation, tissue recovery as well as host metabolic health, presenting a synergistic therapeutic strategy to treat severe COVID-19, particularly in patients with underlying metabolic disease.
- |||||||||| azemiglitazone (MSDC-0602K) / Cirius Therap
Simultaneously targeting hyperinflammation and hyperglycemia following respiratory viral infection (Exhibit Hall; P1047) - Apr 8, 2022 - Abstract #IMMUNOLOGY2022IMMUNOLOGY_2007; scRNA-seq analysis revealed that MSDC treatment reduced lung macrophage inflammation, and myeloid-specific ablation of MPC2 led to dampened lung inflammation. Further, MSDC inhibited human lung macrophage inflammatory responses following SARS-CoV-2 infection, and dampened inflammation in lung autopsies of COVID-19 patients. Mechanistically, MSDC treatment destabilized HIF-1a protein, a transcription factor promoting inflammatory responses of lung macrophages, by repressing cellular Acetyl-CoA levels and HIF-1a acetylation. Our results suggest that MSDC has the great potential to treat severe COVID-19 or other respiratory viral infection, particularly in patients with underlying metabolic conditions, by simultaneously repressing hyper-cytokinemia and hyperglycemia.
- |||||||||| Farxiga (dapagliflozin) / Ono Pharma, AstraZeneca
Clinical, Review, Journal: Non-Alcoholic Steatohepatitis (NASH) - A Review of a Crowded Clinical Landscape, Driven by a Complex Disease. (Pubmed Central) - Feb 2, 2022 At the time of writing this review, only Zydus Cadila's new drug application for Saroglitazar had been approved (2020) for NASH therapy in India...Obeticholic acid (Intercept Pharmaceuticals), Cenicriviroc (Allergan), Aramchol (Galmed Pharmaceuticals), Resmetirom (Madrigal Pharmaceuticals), Dapagliflozin and Semaglutide (Novo Nordisk) are in advanced Phase 3 clinical trials, while Belapectin (Galectin Therapeutics), MSDC-0602K (Cirius Therapeutics), Lanifibranor (Inventiva), Efruxifermin (Akero) and Tesamorelin (Theratechnologies) are expected to start Phase 3 trials soon...Hence, the development of a single therapy for NASH seems challenging and unlikely, despite the plethora of later stage trials due to report. We therefore predict that clinical, patient and company interest in pipeline and next-generation therapies will remain high for some time to come.
- |||||||||| azemiglitazone (MSDC-0602K) / Cirius Therap
Clinical, Journal: Suboptimal reliability of liver biopsy evaluation has implications for randomized clinical trials. (Pubmed Central) - Nov 16, 2021 Reliability of hepatopathologists' liver biopsy evaluation using currently accepted criteria is suboptimal. This lack of reliability may affect NASH pivotal studies by introducing patients who do not meet NASH study entry criteria, misclassifying fibrosis subgroups, and attenuating apparent treatment effects.
- |||||||||| azemiglitazone (MSDC-0602K) / Cirius Therap
Trial completion date, Trial primary completion date: A Study of MSDC-0602K to Assess Glycemic Control and Cardiovascular Outcomes in Patients With Pre-T2D or T2D and NAFLD/NASH (clinicaltrials.gov) - Jan 15, 2021 P3, N=1800, Not yet recruiting, Our results (i) supported the role of TAG/FA cycling in WAT in the beneficial additive effects of Omega-3 and TZDs on metabolism of diet-induced obese mice, and (ii) showed differential modulation of WAT gene expression and metabolism by the two TZDs, depending also on Omega-3. Trial completion date: Jul 2023 --> Nov 2023 | Trial primary completion date: Jul 2023 --> Nov 2023
- |||||||||| azemiglitazone (MSDC-0602K) / Cirius Therap
Enrollment change, Trial completion date, Trial primary completion date: A Study of MSDC-0602K to Assess Glycemic Control and Cardiovascular Outcomes in Patients With Pre-T2D or T2D and NAFLD/NASH (clinicaltrials.gov) - Jul 20, 2020 P3, N=1800, Not yet recruiting, This lack of reliability may affect NASH pivotal studies by introducing patients who do not meet NASH study entry criteria, misclassifying fibrosis subgroups, and attenuating apparent treatment effects. N=3600 --> 1800 | Trial completion date: Dec 2021 --> Jul 2023 | Trial primary completion date: Dec 2021 --> Jul 2023
- |||||||||| MSDC-0602K / Cirius Therap
[VIRTUAL] The New Insulin Sensitizer MSDC-0602K Synergizes with the GLP-1 Receptor Agonist Liraglutide () - May 18, 2020 - Abstract #ADA2020ADA_2105; Isolated islets from lean, naïve mice showed no defect in glucose-stimulated insulin secretion with 0602K treatment, suggesting that the lowered insulinemia in vivo is due to corrected insulin resistance rather than direct inhibition of insulin secretion.In conclusion, the new insulin sensitizer MSDC-0602K improves insulinemia and helps to restore islet insulin content when used alone or in combination with Liraglutide. Glucose tolerance displayed additive effects with combined 0602K+Lira treatment.
- |||||||||| MSDC-0602K / Cirius Therap
[VIRTUAL] MSDC-0602k, a New Oral Insulin Sensitizer in Insulin Resistant NASH Patients with and without Type 2 Diabetes (T2D) () - May 18, 2020 - Abstract #ADA2020ADA_1866; The ratio of C-peptide/FPI increased vs. placebo at end of study (8.54 ± 0.49, 9.69 ± 0.44, 10.45 ± 0.43, and 10.9 ± 0.53 for placebo and the three dose groups, respectively) suggesting both decreased need for secreted insulin and increased clearance of insulin. These data suggest that the new generation insulin sensitizer MSDC-0602K, focused toward MPC and away from PPAR, may be useful to treat patients suffering from combined fatty liver disease and T2D and highlight the importance of FPI.
- |||||||||| azemiglitazone (MSDC-0602K) / Cirius Therap
Trial completion: EMMINENCE: A Study to Evaluate the Safety, Tolerability & Efficacy of MSDC-0602K in Patients With NASH (clinicaltrials.gov) - Jul 23, 2019 P2, N=402, Completed, MSDC-0602K treatment safely produced significant positive effects on glycemic control, and consistent improvement in liver enzymes and non-invasive markers of NASH with a dose-dependent trend in histopathological findings, supporting further development in patients with NASH and T2D. Active, not recruiting --> Completed
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