- |||||||||| oltipraz (PMK-N01GI1) / Canopus BioPharma, Pharmaking
Preclinical, Journal: Effects of Oltipraz on the Glycolipid Metabolism and the Nrf2/HO-1 Pathway in Type 2 Diabetic Mice. (Pubmed Central) - Dec 10, 2024
In summary, OLTI improves blood glucose and insulin resistance, decreases blood lipid metabolism, reduces inflammation and apoptosis, suppresses oxidative stress through the Nrf2/HO-1 signaling pathway, mitigates pancreatic and liver tissue injury, and enhances pancreatic ?-cell insulin secretion, thereby mitigating T2DM symptoms. Moreover, Reg3g could be an important target for OLTI treatment of T2DM.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus BioPharma, Pharmaking
Journal: Heat exposure promotes sarcopenia via gut microbiota-derived metabolites. (Pubmed Central) - Oct 29, 2024
And Nrf2 activator (Oltipraz) supplementation alleviates muscle atrophy and dysfunction induced by heat exposure. Our findings reveal the detrimental effects of heat exposure on muscle function and provide new strategies for treating sarcopenia.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus BioPharma, Pharmaking
Journal: NRF2-HIF2? Signaling Attenuates Endothelial Cell Senescence and Maintains Intercellular Junctions in Diabetes. (Pubmed Central) - Aug 8, 2024
Through its simultaneous modulation of NRF2 and HIF-2?, Oltipraz significantly reduces cellular senescence and prevents the deterioration of intercellular junctions in HUVECs subjected to high glucose concentrations (25 mM). Our research positions Oltipraz as a promising therapeutic candidate for mitigating diabetes-induced vascular endothelial damage, potentially offering benefits against diabetes-related atherosclerosis and valvular calcification.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus BioPharma, Pharmaking
Review, Journal: Aflatoxin B induces infertility, fetal deformities, and potential therapies. (Pubmed Central) - Jan 29, 2024
Substances such as esculin, selenium, gynandra extract, vitamins C and E, oltipraz, and CDDO-Im are potential therapies for AFB. Thus, this review elucidates the pivotal pathogenic roles of AFB in infertility, fetal deformities, and potential therapies because AFB toxicity is a key problem globally.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus BioPharma, Pharmaking
Journal: Mechanism of Nrf2/miR338-3p/TRAP-1 pathway involved in hyperactivation of synovial fibroblasts in patients with osteoarthritis. (Pubmed Central) - Nov 5, 2023
It was confirmed by in vitro assays that oltipraz (agonists of Nrf2) treatment effectively inhibited the hyperactivation of HFLS induced by TGF-?1, and the effects of oltipraz could be reversed by the exogenous TRAP-1. In short, our research has revealed for the first time that Nrf2/miR338-3p/TRAP-1 pathway was involved in hyperactivation of HFLS in OA patients, Nrf2 has the potential to be used as therapy and new drug target of OA.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus BioPharma, Pharmaking
Preclinical, Journal: Efficacy of oltipraz in preventing acetaminophen-induced liver injury in mice. (Pubmed Central) - Aug 3, 2023
This suggests that NQO1 is responsible for the enhanced GSH recovery and protection against APAP-induced liver injury seen in OPZ-treated mice. In summary, OPZ protects against APAP-induced liver injury by inducing NQO1 expression and resulting in improved GSH recovery.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus Biopharma, Pharmaking
Journal: Stanniocalcin1 knockdown induces ferroptosis and suppresses glycolysis in prostate cancer via the Nrf2 pathway. (Pubmed Central) - Jan 3, 2023
Nrf2 pathway activator, Oltipraz, upregulated Nrf2, total NQO1, and HO-1 expressions in PC-3 cells and DU145 cells...Finally, STC1 knockdown restrained the tumor volume, tumor weight, and glycolysis in prostate cancer in vivo. Thus, STC1/Nrf2 pathway is a vital pathway to induce ferroptosis and suppress glycolysis in prostate cancer.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus Biopharma, Pharmaking
Journal: 17β-estradiol plays the anti-osteoporosis role via a novel ESR1-Keap1-Nrf2 axis-mediated stress response activation and Tmem119 upregulation. (Pubmed Central) - Jan 3, 2023
Nrf2 re-activation induced by the pyrazinyl dithiolethione oltipraz significantly rescued the cell phenotype of estrogen-deficient BMSCs in vitro and ex vivo...Conversely, Nrf2 knockout largely blocked the bone anabolic effect of 17β-estradiol in vivo and ex vivo. This study provides insight into the mechanisms whereby estrogen prevents osteoporosis through promoting osteoblastic bone formation via Nrf2-mediated activation of antioxidant signaling and upregulation of Tmem119, and thus provides evidence for Nrf2 as a potential target for clinical prevention and treatment of menopause-related osteoporosis.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus Biopharma, Pharmaking
Journal: Elucidating the Anti-Tumorigenic Efficacy of Oltipraz, a Dithiolethione, in Glioblastoma. (Pubmed Central) - Oct 22, 2022
However, there was no alteration in body weight, organ ratio, and biochemical parameters, reflecting the absence of any toxicity otherwise. Together, our findings could demonstrate the promising chemotherapeutic efficacy of Olt with potential implications in treating GBM.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus BioPharma, Pharmaking
Trial completion, Trial completion date, Trial primary completion date: Oltipraz for Liver Fat Reduction in Patients With Non-alcoholic Fatty Liver Disease Except for Liver Cirrhosis (clinicaltrials.gov) - Oct 6, 2022
P3, N=146, Completed,
Together, our findings could demonstrate the promising chemotherapeutic efficacy of Olt with potential implications in treating GBM. Unknown status --> Completed | Trial completion date: Oct 2021 --> Sep 2022 | Trial primary completion date: Oct 2020 --> Sep 2022
- |||||||||| oltipraz (PMK-N01GI1) / Canopus Biopharma, Pharmaking
Journal: Cartilage targeting therapy with reactive oxygen species-responsive nanocarrier for osteoarthritis. (Pubmed Central) - Sep 28, 2022
Inspired by oxidative stress in the pathogenesis of osteoarthritis, we firstly testified the antioxidant capacity of a synthetic small molecule compound, oltipraz (OL), to the chondrocytes treated by IL-1β...Animal experiments further confirmed the great cartilage-protecting ability of MSN-OL through upregulating the expression of Nrf2/HO-1 signaling pathway without obvious toxicity. In summary, this study provided a delivery system through ROS-responsive regulation of the therapeutic agents into chondrocytes of the cartilage, and confirmed the exact biological mechanisms of this innovative strategy.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus Biopharma, Pharmaking
Preclinical, Journal: Oltipraz ameliorates the progression of steatohepatitis in Nrf2-null mice fed a high-fat diet. (Pubmed Central) - Apr 12, 2022
These histopathological findings approximately corresponded to the data of mRNA expression of tumor necrosis factor α, monocyte chemoattractant protein-1, Timp-1, and collagen type 1α1. These results indicated that oltipraz administration ameliorated liver injury by Nrf2 independent manner in a model of steatohepatitis generated by Nrf2-null mice with high-fat diet.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus Biopharma, Pharmaking
Journal: Inhibition of Nrf2 degradation alleviates age-related osteoporosis induced by 1,25-Dihydroxyvitamin D deficiency. (Pubmed Central) - Jan 6, 2022
To further validate that the Nrf2-Keap1 pathway serves as the key mediator in the anabolic effect of 1,25(OH)D on bone, Nrf2 mice, or hBM-MSCs with shRNA-mediated Nrf2-knockdown, were treated with 1,25(OH)D; we found that Nrf2 knockout largely blocked the bone anabolic effect of 1,25(OH)D in vivo and ex vivo, and Nrf2 knockdown in hBM-MSCs markedly blocked the role of 1,25(OH)D in inhibiting oxidative stress and promoting osteogenic differentiation and bone formation. This study provides insight into the mechanism whereby 1,25(OH)D postpones age-related osteoporosis via VDR-mediated activation of Nrf2-antioxidant signaling and inhibition of oxidative stress, and thus provides evidence for oltipraz as a potential reagent for clinical prevention and treatment of age-related osteoporosis.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus Biopharma, Pharmaking
Journal: CoCrMo-Nanoparticles induced peri-implant osteolysis by promoting osteoblast ferroptosis via regulating Nrf2-ARE signalling pathway. (Pubmed Central) - Dec 25, 2021
This study provides insight into the mechanism whereby 1,25(OH)D postpones age-related osteoporosis via VDR-mediated activation of Nrf2-antioxidant signaling and inhibition of oxidative stress, and thus provides evidence for oltipraz as a potential reagent for clinical prevention and treatment of age-related osteoporosis. These results indicate that CoNPs promote osteoblast ferroptosis by regulating the Nrf2-ARE signalling pathway, which suggests a new mechanism underlying PIO and represents a potential therapeutic approach for AL.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus Biopharma, Pharmaking
Journal, IO biomarker: G/M cell cycle arrest and apoptosis induced by COH-203 in human promyelocytic leukemia HL-60 cells. (Pubmed Central) - Oct 25, 2021
The combretastatin A-4/oltipraz hybrid (COH), 5-(3-amino-4-methoxyphenyl)-4-(3,4,5-trimethoxyphenyl)-3H-1,2-dithiole-3-one (COH-203) is one of the COH compounds synthesized by our previous study, which has been reported to affect a number of cancer cell lines, such as SGC-7901, KB, HT-1080, HepG2, SMMC-7721 and BEL-7402...In addition, treatment with COH-203 resulted in downregulated expression of Bcl-2. This result revealed that COH-203-induced apoptosis in HL-60 cells may occur via the mitochondrial pathway in a caspase-dependent manner.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus Biopharma, Pharmaking
Journal: Novel adipokine asprosin modulates browning and adipogenesis in white adipose tissue. (Pubmed Central) - Aug 21, 2021
Our findings suggest that novel adipokine asprosin negatively regulated browning and elevate lipid deposition in adipose tissue via a Nrf2-mediated mechanism. Asprosin may be a promising target for the prevention and treatment of obesity and other metabolic diseases.
- |||||||||| cisplatin / Generic mfg., paclitaxel / Generic mfg.
Preclinical, Journal: Targeting dormant ovarian cancer cells in vitro and in an in vivo mouse model of platinum resistance. (Pubmed Central) - Aug 14, 2021
Continued treatment with carboplatin was accompanied by an increase in tumor signal while there was little or no increase in tumor signal observed with subsequent treatment with UCN-01 or Oltipraz. Taken together, our findings suggest that genes involved in mitochondrial function in spheroids may be an important therapeutic target in preventing disease recurrence.
- |||||||||| RSL3 / Stanford University
Journal: Suppressing the KIF20A/NUAK1/Nrf2/GPX4 signaling pathway induces ferroptosis and enhances the sensitivity of colorectal cancer to oxaliplatin. (Pubmed Central) - Jul 24, 2021
We evaluated CRC cells with acquired oxaliplatin resistance (HCT116-Or) or congenital resistance (H716) to determine whether a ferroptosis inducer (RSL3) or inhibitor (liproxstatin-1) could modulate the effects of oxaliplatin...Silencing KIF20A enhanced cellular sensitivity to oxaliplatin both in vivo and in vitro, and silencing KIF20A also suppressed NUAK1 activation, while a NUAK1 agonist (ETC-1002) could reverse the oxaliplatin sensitivity of KIF20A-silenced cells...Applying a Nrf2 agonist (oltipraz) also reversed the oxaliplatin sensitivity of NUAK1-silenced cells. Therefore, cellular ferroptosis may be inhibited via the KIF20A/NUAK1/PP1β/GPX4 pathway in CRC cells, which may underly the resistance of CRC to oxaliplatin.
- |||||||||| paclitaxel / Generic mfg.
Journal: Nrf2 activation ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain. (Pubmed Central) - May 29, 2021
Repeated injection of oltipraz caused further elevation of the expression levels of Nrf2 and HO-1 in the spinal cord of PINP rats, which was reversed by pre-injection of trigonelline. These results demonstrate that oltipraz ameliorates PINP via activating Nrf2/HO-1-signaling pathway in the spinal cord.
- |||||||||| Zarzio (filgrastim biosimilar) / Novartis, oltipraz (PMK-N01GI1) / Canopus Biopharma, Pharmaking
[VIRTUAL] NRF2 AS A THERAPEUTIC TARGET IN ACUTE LEUCEMIA – IN VITRO STUDIES WITH OLTIPRAZ () - May 13, 2021 - Abstract #EHA2021EHA_829;
Conclusion Our results demonstrate that lymphoid and myeloid acute leukemias were sensitive to NRF2 modulation using Oltipraz, suggesting that this drug may constitute a new therapeutic approach in these hematological neoplasms. However, the drug efficacy is cell type dependent and could be also related with molecular/genetic characteristics of the leukemia.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus Biopharma, Pharmaking
Journal: Modulation of Oxidative Stress and Inflammation in the Aged Lacrimal Gland. (Pubmed Central) - Feb 20, 2021
A separate group of 15.5 to 17 months of age C57BL/6 mice received a diet containing an Nrf2 inducer (Oltipraz) for 8 weeks...The findings provide novel insight into the development of chronic, low-grade inflammation and oxidative stress in age-related dry eye. New therapies targeting oxidative stress pathways will be valuable in treating age-related dry eye.
- |||||||||| GS5423 / Rockefeller University, National Institute of Allergy and Infectious Diseases, Gilead, oltipraz (PMK-N01GI1) / Canopus Biopharma, Pharmaking
Biomarker, Journal: Ubiquitin-Like Modifier Activating Enzyme 1 as a Novel Diagnostic and Prognostic Indicator That Correlates With Ferroptosis and the Malignant Phenotypes of Liver Cancer Cells. (Pubmed Central) - Dec 22, 2020
Furthermore, blocking UBA1 strikingly repressed the protein expression levels of Nrf2, HO-1, NQO1, and FTH1 in the Nrf2 signal transduction pathway. Our findings demonstrated that UBA1 participates in the development of HCC by modulating Huh7 phenotypes and ferroptosis via the Nrf2 signal transduction pathway and might be a promising diagnostic and prognostic indicator for HCC.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus Biopharma, Pharmaking
Biomarker, Journal: Mining a human transcriptome database for chemical modulators of NRF2. (Pubmed Central) - Nov 12, 2020
A gene expression biomarker was built from statistically-filtered gene lists derived from microarray experiments in primary human hepatocytes and cancer cell lines exposed to NRF2-activating chemicals (oltipraz, sulforaphane, CDDO-Im) or in which the NRF2 suppressor Keap1 was knocked down by siRNA...Using a NRF2-responsive reporter gene in HepG2 cells, we confirmed the activity of a set of chemicals predicted using the biomarker. The biomarker will be useful for future gene expression screening studies of environmentally-relevant chemicals.
- |||||||||| dimethyl fumarate / Generic mfg.
Preclinical, Journal, HEOR: Comparative effectiveness of 4 natural and chemical activators of Nrf2 on inflammation, oxidative stress, macrophage polarization, and bactericidal activity in an in vitro macrophage infection model. (Pubmed Central) - Sep 1, 2020
We first compared the capacity of sulforaphane (SFN), wogonin (WG), oltipraz (OTZ), and dimethyl fumarate (DMF) to induce the nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of the antioxidant, anti-inflammatory response pathways...Conversely, OTZ exhibited pro-oxidant and proinflammatory properties, and affected intracellular survival of E. coli in THP-1-derived macrophages. Altogether, we provide new potential therapeutic alternatives in treating inflammation and bacterial infection.
- |||||||||| Tecfidera (dimethyl fumarate) / Biogen
Biomarker, Clinical, Review, Journal: Current Landscape of NRF2 Biomarkers in Clinical Trials. (Pubmed Central) - Aug 14, 2020
This review focuses on results from clinical trials with four agents known to target NRF2 signaling in preclinical studies (dimethyl fumarate, bardoxolone methyl, oltipraz, and sulforaphane), and evaluates the successes and limitations of biomarkers focused on expression of NRF2 target genes and others, inflammation and oxidative stress biomarkers, carcinogen metabolism and adduct biomarkers in unavoidably exposed populations, and targeted and untargeted metabolomics. While no biomarkers excel at defining pharmacodynamic actions in this setting, it is clear that these four lead clinical compounds do touch the NRF2 pathway in humans.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus Biopharma, Pharmaking
Journal: Acetaminophen-induced reduction in glutathione-S-transferase A1 in hepatocytes: A role for hepatic nuclear factor 1α and its response element. (Pubmed Central) - Jul 16, 2020
Contrastingly, administration of oltipraz alleviated cells damage with GSTA1 mRNA level elevating relative to hepatotoxicity induced by APAP...However, the luciferase activity had no change with the variation of nuclear HNF-1α when the cells transfected with the plasmid of pGSTA1-ΔHNF1-LUC in which the HRE was mutated. In conclusion, HNF-1α could affect the transcription of GSTA1 and HNF-1 response element in the GSTA1 promoter region, which is functionally active for the GSTA1 transcription.
- |||||||||| oltipraz (PMK-N01GI1) / Canopus Biopharma, Pharmaking
Journal: Identification of Pannexin 2 as a Novel Marker Correlating with Ferroptosis and Malignant Phenotypes of Prostate Cancer Cells. (Pubmed Central) - Jun 19, 2020
However, these effects were rescued by Nrf2 activator, oltipraz...We established that silencing PANX2 remarkably reduced protein expression levels in members of Nrf2 signaling pathway (Nrf2, HO-1, and FTH1). Our study demonstrated that PANX2 is implicated in the pathogenesis of PCa, which regulates malignant phenotypes and ferroptosis through Nrf2 signaling pathway, and maybe a potential therapeutic target for PCa.
- |||||||||| Tecfidera (dimethyl fumarate) / Biogen
Preclinical, Journal: Nrf2 Activation Protects Mouse Beta Cells from Glucolipotoxicity by Restoring Mitochondrial Function and Physiological Redox Balance. (Pubmed Central) - May 6, 2020
Oltipraz (10 μmol/L) or dimethyl fumarate (DMF, 50 μmol/L) leads to nuclear accumulation of Nrf2, restores mitochondrial activity and glucose-dependent ROS turnover, and antagonizes glucolipotoxicity-induced inhibition of insulin release and apoptosis...As our data show that this maintains glucose-stimulated insulin secretion, targeting Nrf2 might be suited to ameliorate progression of type 2 diabetes mellitus. By contrast, nonstressed beta cells do not benefit from Nrf2 activation, thus underlining the importance of physiological shifts in ROS homeostasis for the regulation of beta cell function.
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