keyword
MENU ▼
Read by QxMD icon Read
search

bardoxolone methyl

keyword
https://www.readbyqxmd.com/read/28994286/a-novel-derivative-of-bardoxolone-methyl-improves-safety-for-treatment-of-diabetic-nephropathy
#1
Zhangjian Huang, Yi Mou, Xiaojun Xu, Di Zhao, Yisheng Lai, Yuwen Xu, Cen Chen, Ping Li, Sixun Peng, Jide Tian, Yihua Zhang
Currently, no effective and safe medicines are available to treat diabetic nephropathy (DN). Bardoxolone methyl (CDDO-Me) has displayed promising anti-DN activity but serious side-effects in the clinical trial, probably because the highly reactive α-cyano-α,β-unsaturated ketone (CUK) in ring A of CDDO-Me can covalently bind to thiol functionalities in many biomacromolecules. In this study, we designed and synthesized a γ-glutamyl transpeptidase (GGT)-based and CUK-modified derivative 2 of CDDO-Me to address this issue...
October 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28978980/role-of-bardoxolone-methyl-a-nuclear-factor-erythroid-2-related-factor-2-activator-in-aldosterone-and-salt-induced-renal-injury
#2
Mikako Hisamichi, Atsuko Kamijo-Ikemori, Takeshi Sugaya, Seiko Hoshino, Kenjiro Kimura, Yugo Shibagaki
The aim of this study was to investigate the renoprotective effect of bardoxolone methyl (BM), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator with an antioxidant effect, in a salt-sensitive hypertension model induced by aldosterone (Ald) and salt. Tubulointerstitial damage with urinary liver-type fatty acid-binding protein (L-FABP) was evaluated using human L-FABP chromosomal transgenic (L-FABP(+/-)) male mice. The mice in the Ald group (n=7) received systemic Ald infusions via an osmotic minipump and were given 1% NaCl water for 35 days...
October 5, 2017: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/28901514/multimodal-actions-of-the-phytochemical-sulforaphane-suppress-both-ar-and-ar-v7-in-22rv1-cells-advocating-a-potent-pharmaceutical-combination-against-castration-resistant-prostate-cancer
#3
Namrata Khurana, Hogyoung Kim, Partha K Chandra, Sudha Talwar, Pankaj Sharma, Asim B Abdel-Mageed, Suresh C Sikka, Debasis Mondal
Prostate cancer (PCa) cells expressing full-length androgen receptor (AR-FL) are susceptible to androgen deprivation therapy (ADT). However, outgrowth of castration-resistant prostate cancer (CRPC) can occur due to the expression of constitutively active (ligand-independent) AR splice variants, particularly AR-V7. We previously demonstrated that sulforaphane (SFN), an isothiocyanate phytochemical, can decrease AR-FL levels in the PCa cell lines, LNCaP and C4-2B. Here, we examined the efficacy of SFN in targeting both AR-FL and AR-V7 in the CRPC cell line, CWR22Rv1 (22Rv1)...
August 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28886135/differential-regulation-of-innate-immune-cytokine-production-through-pharmacological-activation-of-nuclear-factor-erythroid-2-related-factor-2-nrf2-in-burn-patient-immune-cells-and-monocytes
#4
Timothy K Eitas, Wesley Stepp, Lucas Sjeklocha, Clayton Long, Caitlin Riley, James Callahan, Yolanda Sanchez, Peter Gough, Laquanda Knowlin, David van Duin, Shiara Ortiz-Pujols, Samuel Jones, Robert Maile, Zhi Hong, Scott Berger, Bruce Cairns
Burn patients suffer from immunological dysfunction for which there are currently no successful interventions. Similar to previous observations, we find that burn shock patients (≥15% Total Burn Surface Area (TBSA) injury) have elevated levels of the innate immune cytokines Interleukin-6 (IL-6) and Monocyte Chemoattractant Protein-1 (MCP-1)/CC-motif Chemokine Ligand 2(CCL2) early after hospital admission (0-48 Hours Post-hospital Admission (HPA). Functional immune assays with patient Peripheral Blood Mononuclear Cells (PBMCs) revealed that burn shock patients (≥15% TBSA) produced elevated levels of MCP-1/CCL2 after innate immune stimulation ex vivo relative to mild burn patients...
2017: PloS One
https://www.readbyqxmd.com/read/28753294/electrophilic-triterpenoid-enones-a-comparative-thiol-trapping-and-bioactivity-study
#5
Danilo Del Prete, Orazio Taglialatela-Scafati, Alberto Minassi, Carmina Sirignano, Cristina Cruz, Maria L Bellido, Eduardo Muñoz, Giovanni Appendino
Bardoxolone methyl (1) is the quintessential member of triterpenoid cyanoacrylates, an emerging class of bioactive compounds capable of transient covalent binding to thiols. The mechanistic basis for this unusual "pulsed reactivity" profile and the mode of its biological translation are unknown. To provide clues on these issues, a series of Δ(1)-dehydrooleanolates bearing an electron-withdrawing group at C-2 (7a-m) were prepared from oleanolic acid (3a) and comparatively investigated in terms of reactivity with thiols and bioactivity against a series of electrophile-sensitive transcription factors (Nrf2, NF-κB, STAT3)...
August 25, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28678272/design-synthesis-and-biological-activity-of-second-generation-synthetic-oleanane-triterpenoids
#6
Liangfeng Fu, Qi-Xian Lin, Evans O Onyango, Karen T Liby, Michael B Sporn, Gordon W Gribble
We report the synthesis and biological activity of C-24 demethyl CDDO-Me 2 and the C-28 amide derivatives 3 and 4, which are analogues of the anti-inflammatory synthetic triterpenoid bardoxolone methyl (CDDO-Me) 1. Demethylation of the C-24 methyl group was accomplished via "abnormal Beckmann" rearrangement and subsequent ring A reformation. Amides 3 and 4 were found to be potent inhibitors of the production of the inflammatory mediator NO in vitro.
July 19, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28438659/the-nrf2-activator-dh404-attenuates-adverse-ventricular-remodeling-post-myocardial-infarction-by-modifying-redox-signalling
#7
Kristen J Bubb, Cindy Kok, Owen Tang, Nathalie B Rasko, Asa B Birgisdottir, Thomas Hansen, Rebecca Ritchie, Ravinay Bhindi, Scott A Reisman, Colin Meyer, Keith Ward, Keyvan Karimi Galougahi, Gemma A Figtree
BACKGROUND: The novel synthetic triterpenoid, bardoxolone methyl, has the ability to upregulate cytoprotective proteins via induction of the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. This makes it a promising therapeutic agent in disease states characterized by dysregulated oxidative signalling. We have examined the effect of a Nrf2 activator, dihydro-CDDO-trifluoroethyl amide (DH404), a derivative of bardoxolone methyl, on post-infarct cardiac remodeling in rats. METHODS/RESULTS: DH404, administered from day 2 post myocardial infarction (MI: 30min transient ischemia followed by reperfusion) resulted in almost complete protection against adverse ventricular remodeling as assessed at day 28 (left ventricular end-systolic area: sham 0...
April 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28375181/dietary-metabolites-and-chronic-kidney-disease
#8
REVIEW
Sho Hasegawa, Tzu-Ming Jao, Reiko Inagi
Dietary contents and their metabolites are closely related to chronic kidney disease (CKD) progression. Advanced glycated end products (AGEs) are a type of uremic toxin produced by glycation. AGE accumulation is not only the result of elevated glucose levels or reduced renal clearance capacity, but it also promotes CKD progression. Indoxyl sulfate, another uremic toxin derived from amino acid metabolism, accumulates as CKD progresses and induces tubulointerstitial fibrosis and glomerular sclerosis. Specific types of amino acids (d-serine) or fatty acids (palmitate) are reported to be closely associated with CKD progression...
April 4, 2017: Nutrients
https://www.readbyqxmd.com/read/28277986/bardoxolone-methyl-inhibits-migration-and-metabolism-in-mcf7-cells
#9
Alaa Refaat, Chathyan Pararasa, Muhammed Arif, James E P Brown, Amtul Carmichael, Sameh S Ali, Hiroaki Sakurai, Helen R Griffiths
Bardoxolone-methyl (BAR) is reported to have anti-inflammatory, anti-proliferative and anti-fibrotic effects. BAR activates Nrf2 and may ameliorate oxidative stress through induction of antioxidant genes. However, off-target effects, probably concentration and NFkB-dependent, have limited the clinical use of BAR. Nrf2 regulates expression of antioxidant and mitochondrial genes and has been proposed as a target for both obesity and breast cancer. Therefore, we explored whether BAR can alter migration and proliferation in the MCF7 cell line and whether metabolic function is affected by BAR...
February 2017: Free Radical Research
https://www.readbyqxmd.com/read/28275049/bardoxolone-methyl-and-a-related-triterpenoid-downregulate-cmyc-expression-in-leukemia-cells
#10
Un-Ho Jin, Yating Cheng, Beiyan Zhou, Stephen Safe
Structurally related pentacyclic triterpenoids methyl 2-cyano-3,12-dioxoolean-1,9-dien-28-oate [bardoxolone-methyl (Bar-Me)] and methyl 2-trifluoromethyl-3,11-dioxoolean-1,12-dien-30-oate (CF3DODA-Me) contain 2-cyano-1-en-3-one and 2-trifluoromethyl-1-en-3-one moieties, respectively, in their A-rings and differ in the position of their en-one structures in ring C. Only Bar-Me forms a Michael addition adduct with glutathione (GSH) and inhibits IKKβ phosphorylation. These differences may be due to steric hindrance by the 11-keto group in CF3DODA-Me, which prevents Michael addition by the conjugated en-one in the A-ring...
May 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28253885/the-nuclear-factor-erythroid-derived-2-like-2-nrf2-activator-dh404-protects-against-diabetes-induced-endothelial-dysfunction
#11
Arpeeta Sharma, Luddwi Rizky, Nada Stefanovic, Mitchel Tate, Rebecca H Ritchie, Keith W Ward, Judy B de Haan
BACKGROUND: Vascular dysfunction is a pivotal event in the development of diabetes-associated vascular disease. Increased inflammation and oxidative stress are major contributors to vascular dysfunction. Nrf2, a master regulator of several anti-oxidant genes and a suppressor of inflammatory NF-κB, has potential as a target to combat oxidative stress and inflammation. The aim of this study was to investigate the effects of a novel Nrf2 activator, the bardoxolone methyl derivative dh404, on endothelial function in vitro and in vivo...
March 3, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28097824/mechanisms-of-metabolic-memory-and-renal-hypoxia-as-a-therapeutic-target-in-diabetic-kidney-disease
#12
REVIEW
Yosuke Hirakawa, Tetsuhiro Tanaka, Masaomi Nangaku
Diabetic kidney disease (DKD) is a worldwide public health problem. The definition of DKD is under discussion. Although the term DKD was originally defined as 'kidney disease specific to diabetes,' DKD frequently means chronic kidney disease with diabetes mellitus and includes not only classical diabetic nephropathy, but also kidney dysfunction as a result of nephrosclerosis and other causes. Metabolic memory plays a crucial role in the progression of various complications of diabetes, including DKD. The mechanisms of metabolic memory in DKD are supposed to include advanced glycation end-products, deoxyribonucleic acid methylation, histone modifications and non-coding ribonucleic acid including micro ribonucleic acid...
May 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/27979484/microrna-125b-as-a-new-potential-biomarker-on-diagnosis-of-renal-ischemia-reperfusion-injury
#13
REVIEW
Aydın Güçlü, Cengiz Koçak, Fatma E Koçak, Raziye Akçılar, Yavuz Dodurga, Aydın Akçılar, Levent Elmas
BACKGROUND: Acute renal failure is commonly seen in the perioperative period. Ischemia-reperfusion (IR) injury plays a major role in acute renal failure and delayed graft function. MicroRNAs (miRs), which are pivotal modulators of cell activities, offer a major opportunity for affective diagnosis and treatment strategies because they are tissue specific and in the center of gene expression modulation. The effect of bardoxolone methyl (BM) on miR-21, miR-223-5p, and miR-125b in renal IR injury was evaluated in this study...
January 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/27823964/michael-acceptor-containing-drugs-are-a-novel-class-of-5-lipoxygenase-inhibitor-targeting-the-surface-cysteines-c416-and-c418
#14
Isabelle V Maucher, Michael Rühl, Simon B M Kretschmer, Bettina Hofmann, Benjamin Kühn, Jasmin Fettel, Anja Vogel, Karsten T Flügel, Georg Manolikakes, Nadine Hellmuth, Ann-Kathrin Häfner, Vahid Golghalyani, Ann-Katrin Ball, Matthias Piesche, Carmela Matrone, Gerd Geisslinger, Michael J Parnham, Michael Karas, Dieter Steinhilber, Jessica Roos, Thorsten J Maier
Recently, we published that nitro-fatty acids (NFA) are potent electrophilic molecules which inhibit 5-lipoxygenase (5-LO) by interacting catalytically with cysteine residues next to a substrate entry channel. The electrophilicity is derived from an intramolecular Michael acceptor moiety consisting of an electron-withdrawing group in close proximity to a double bond. The potential of the Michael acceptor moiety to interact with functionally relevant cysteines of proteins potentially renders them effective and sustained enzyme activity modulators...
February 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27818722/nrf2-is-an-attractive-therapeutic-target-for-retinal-diseases
#15
REVIEW
Yasuhiro Nakagami
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that binds to antioxidant response elements located in the promoter region of genes encoding many antioxidant enzymes and phase II detoxifying enzymes. Activation of Nrf2 functions is one of the critical defensive mechanisms against oxidative stress in many species. The retina is constantly exposed to reactive oxygen species, and oxidative stress is a major contributor to age-related macular diseases. Moreover, the resulting inflammation and neuronal degeneration are also related to other retinal diseases...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27474227/a-novel-nuclear-factor-erythroid-2-related-factor-2-nrf2-activator-rs9-attenuates-brain-injury-after-ischemia-reperfusion-in-mice
#16
Keita Yamauchi, Yusuke Nakano, Takahiko Imai, Toshinori Takagi, Kazuhiro Tsuruma, Masamitsu Shimazawa, Toru Iwama, Hideaki Hara
Recanalization of occluded vessels leads to ischemia-reperfusion injury (IRI), with oxidative stress as one of the main causes of injury, despite the fact that recanalization therapy is the most effective treatment for ischemic stroke. The nuclear factor erythroid 2-related factor 2 (Nrf2) is one of the transcription factors which has an essential role in protection against oxidative stress. RS9 is a novel Nrf2 activator obtained from bardoxolone methyl (BARD), an Nrf2 activator that has already been tested in a clinical trial, using a biotransformation technique...
October 1, 2016: Neuroscience
https://www.readbyqxmd.com/read/27417254/bardoxolone-methyl-prevents-obesity-and-hypothalamic-dysfunction
#17
Danielle Camer, Yinghua Yu, Alexander Szabo, Hongqin Wang, Chi H L Dinh, Xu-Feng Huang
High-fat (HF) diet-induced obesity is associated with hypothalamic leptin resistance and low grade chronic inflammation, which largely impairs the neuroregulation of negative energy balance. Neuroregulation of negative energy balance is largely controlled by the mediobasal and paraventricular nuclei regions of the hypothalamus via leptin signal transduction. Recently, a derivative of oleanolic acid, bardoxolone methyl (BM), has been shown to have anti-inflammatory effects. We tested the hypothesis that BM would prevent HF diet-induced obesity, hypothalamic leptin resistance, and inflammation in mice fed a HF diet...
August 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27242339/a-novel-nrf2-activator-from-microbial-transformation-inhibits-radiation-induced-dermatitis-in-mice
#18
Yasuhiro Nakagami, Kayoko Masuda
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that regulates many antioxidants, and we have recently succeeded in obtaining a novel Nrf2 activator, RS9, from microbial transformation. RS9 is categorized as a triterpenoid, and well-known triterpenoids such as RTA 402 (bardoxolone methyl) and RTA 408 have been tested in clinical trials. RTA 408 lotion is currently being tested in patients at risk for radiation dermatitis. This prompted us to study the profiles of RS9 in the skin...
September 2016: Journal of Radiation Research
https://www.readbyqxmd.com/read/26920068/bardoxolone-methyl-prevents-high-fat-diet-induced-colon-inflammation-in-mice
#19
Chi H L Dinh, Yinghua Yu, Alexander Szabo, Qingsheng Zhang, Peng Zhang, Xu-Feng Huang
Obesity induces chronic, low-grade inflammation, which increases the risk of colon cancer. We investigated the preventive effects of Bardoxolone methyl (BARD) on high-fat diet (HFD)-induced inflammation in a mouse colon. Male C57BL/6J mice (n=7) were fed a HFD (HFD group), HFD plus BARD (10 mg/kg) in drinking water (HFD/BARD group), or normal laboratory chow diet (LFD group) for 21 weeks. In HFD mice, BARD reduced colon thickness and decreased colon weight per length. This was associated with an increase in colon crypt depth and the number of goblet cells per crypt...
April 2016: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/26908173/design-and-synthesis-of-irreversible-analogues-of-bardoxolone-methyl-for-the-identification-of-pharmacologically-relevant-targets-and-interaction-sites
#20
Michael H L Wong, Holly K Bryan, Ian M Copple, Rosalind E Jenkins, Pak Him Chiu, Jaclyn Bibby, Neil G Berry, Neil R Kitteringham, Christopher E Goldring, Paul M O'Neill, B Kevin Park
Semisynthetic triterpenoids such as bardoxolone methyl (methyl-2-cyano 3,12-dioxooleano-1,9-dien-28-oate; CDDO-Me) (4) are potent inducers of antioxidant and anti-inflammatory signaling pathways, including those regulated by the transcription factor Nrf2. However, the reversible nature of the interaction between triterpenoids and thiols has hindered attempts to identify pharmacologically relevant targets and characterize the sites of interaction. Here, we report a shortened synthesis and SAR profiling of 4, enabling the design of analogues that react irreversibly with model thiols, as well as the model protein glutathione S-transferase P1, in vitro...
March 24, 2016: Journal of Medicinal Chemistry
keyword
keyword
91967
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"