Evidence
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
J Med Chem. 2024 Jul 12. doi: 10.1021/acs.jmedchem.4c00211. Online ahead of print.
ABSTRACT
Ferroptosis is a promising therapeutic target for injury-related diseases, yet diversity in ferroptosis inhibitors remains limited. In this study, initial structure optimization led us to focus on the bond dissociation enthalpy (BDE) of the N-H bond and the residency time of radical scavengers in a phospholipid bilayer, which may play an important role in ferroptosis inhibition potency. This led to the discovery of compound D1, exhibiting potent ferroptosis inhibition, high radical scavenging, and moderate membrane permeability. D1 demonstrated significant neuroprotection in an oxygen glucose deprivation/reoxygenation (OGD/R) model and reduced infarct volume in an in vivo stroke model upon intravenous treatment. Further screening based on this strategy identified NecroX-7 and Eriodictyol-7-O-glucoside as novel ferroptosis inhibitors with highly polar structural characteristics. This approach bridges the gap between free radical scavengers and ferroptosis inhibitors, providing a foundation for research and insights into novel ferroptosis inhibitor development.
PMID:38996382 | DOI:10.1021/acs.jmedchem.4c00211
![Google](https://www.google.com/images/branding/googlelogo/2x/googlelogo_light_color_92x30dp.png)
![Google Keep](https://www.gstatic.com/images/branding/product/1x/keep_48dp.png)
![Share on Linkedin](https://psychiatryai.com/wp-content/uploads/2023/10/linkedin-logo-png-2048-1.png)
Estimated reading time: 3 minute(s)
Latest: Psychiatryai.com #RAISR4D Evidence
![](/wp-content/uploads/2024/04/bd462cc11bcf0bd0d0d6f1d0f8b7cd04-modified-1.png)
Cool Evidence: Engaging Young People and Students in Real-World Evidence
![](/wp-content/uploads/2024/04/bd462cc11bcf0bd0d0d6f1d0f8b7cd04-modified-1.png)
Real-Time Evidence Search [Psychiatry]
![](/wp-content/uploads/2024/04/pubmed.png)
AI Research
![](/wp-content/uploads/2024/05/Il5nR_nf_400x400-modified-1.png)
Discovery of New Phenyltetrazolium Derivatives as Ferroptosis Inhibitors for Treating Ischemic Stroke: An Example Development from Free Radical Scavengers
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
🌐 90 Days
AI Virtual Reality Related Evidence Matrix
Discovery of 3-((4-Benzylpyridin-2-yl)amino)benzamides as Potent GPR52 G Protein-Biased Agonists Discovery of Potent Multikinase Type-II Inhibitors Targeting CDK5 in the DFG-out Inactive State with Promising Potential against Glioblastoma Ferroptosis in health and disease Pacidusin B isolated from Phyllanthus acidus triggers ferroptotic cell death in HT1080 cells Structure-Based Drug Design of ADRA2A Antagonists Derived from Yohimbine A "Ferroptosis-Amplifier" Hydrogel for Eliminating Refractory Cancer Stem Cells Post-lumpectomy Peroxynitrite-Triggered Carbon Monoxide Donor Improves Ischemic Stroke Outcome by Inhibiting Neuronal Apoptosis and Ferroptosis Brusatol induces ferroptosis to inhibit hepatocellular carcinoma progression by targeting ATF3 Fatty acid-binding protein 5 is a functional biomarker and indicator of ferroptosis in cerebral hypoxia Structure-Activity Studies of 1,2,4-Oxadiazoles for the Inhibition of the NAD+-Dependent Lysine Deacylase Sirtuin 2 Structure-Activity Studies of 1,2,4-Oxadiazoles for the Inhibition of the NAD+-Dependent Lysine Deacylase Sirtuin 2 Discovery of a Highly Potent and Selective BRD9 PROTAC Degrader Based on E3 Binder Investigation for the Treatment of Hematological Tumors The Flavonoid Glycoside from Abrus cantoniensis Hance Alleviates Alcoholic Liver Injury by Inhibiting Ferroptosis in an AMPK-Dependent Manner Novel Inhibitory Site Revealed by XAP044 Mode of Action on the Metabotropic Glutamate 7 Receptor Venus Flytrap Domain Cell-cell contacts prevent t-BuOOH-triggered ferroptosis and cellular damage in vitro by regulation of intracellular calcium Electroacupuncture pretreatment inhibits ferroptosis and inflammation after middle cerebral artery occlusion in rats by activating Nrf2 Fentanyl-Type Antagonist of the μ-Opioid Receptor: Important Role of Axial Chirality in the Active Conformation DMT1 ubiquitination by Nedd4 protects against ferroptosis after intracerebral hemorrhage Evolutionary Multiobjective Molecule Optimization in an Implicit Chemical Space Evolutionary Multiobjective Molecule Optimization in an Implicit Chemical Space Electroacupuncture Inhibits Neural Ferroptosis in Rat Model of Traumatic Brain Injury via Activating System Xc-/GSH/GPX4 Axis Uncovering the ferroptosis related mechanism of laduviglusib in the cell-type-specific targets of the striatum in Huntington's disease Ferroptosis Pathways: Unveiling the Neuroprotective Power of Cistache Deserticola Phenylethanoid Glycosides Identification of potential key ferroptosis- and autophagy-related genes in myelomeningocele through bioinformatics analysis Naphthoquinones and anthraquinones: Exploring their impact on acetylcholinesterase enzyme activity Design and Synthesis of Clinical Candidate PF-06852231 (CVL-231): A Brain Penetrant, Selective, Positive Allosteric Modulator of the M4 Muscarinic Acetylcholine Receptor SRSF2 promotes glioblastoma cell proliferation by inducing alternative splicing of FSP1 and inhibiting ferroptosis SRSF2 promotes glioblastoma cell proliferation by inducing alternative splicing of FSP1 and inhibiting ferroptosis Exploring novel indazole derivatives as ASK1 inhibitors: Design, synthesis, biological evaluation and docking studies Tanshinone _A inhibits ferroptosis via Nrf2 signaling pathway to protect liver in rats of non-alcoholic fatty liver disease Ligand-Directed Labeling of the Adenosine A1 Receptor in Living Cells Molecular Mechanism of Fusarium Fungus Inhibition by Phenazine-1-carboxamide Bohemian Rhapsody of Future Drug Delivery Systems: Rational Changes Necessary for the Next Revolution Wilson Disease: Copper-Mediated Cuproptosis, Iron-Related Ferroptosis, and Clinical Highlights, with Comprehensive and Critical Analysis Update Wilson Disease: Copper-Mediated Cuproptosis, Iron-Related Ferroptosis, and Clinical Highlights, with Comprehensive and Critical Analysis Update Unveiling the Mechanism of Phenamacril Resistance in F. graminearum: Computational and Experimental Insights into the C423A Mutation in FgMyoI Unveiling the Mechanism of Phenamacril Resistance in F. graminearum: Computational and Experimental Insights into the C423A Mutation in FgMyoI Utilization of an optimized AlphaFold protein model for structure-based design of a selective HDAC11 inhibitor with anti-neuroblastoma activity Myeloid derived suppressor cells and macrophages in regulation of immune response in cancer and tumor progression Receptor Ligand-Free Mesoporous Silica Nanoparticles: A Streamlined Strategy for Targeted Drug Delivery across the Blood-Brain Barrier Regulating NCOA4-Mediated Ferritinophagy for Therapeutic Intervention in Cerebral Ischemia-Reperfusion Injury Development of Peptide-Based Probes for Molecular Imaging of the Postsynaptic Density in the Brain Epigenetic Inhibitors as Alzheimer's Disease Therapeutic Agents SLC22A17 as a Cell Death-Linked Regulator of Tight Junctions in Cerebral Ischemia Ultrasound-Based Micro-/Nanosystems for Biomedical Applications Impact of Sacrificial Hydrogen Bonds on the Structure and Properties of Rubber Materials: Insights from All-Atom Molecular Dynamics Simulations Targeting brain-peripheral immune responses for secondary brain injury after ischemic and hemorrhagic stroke Fast transfer of triplet to doublet excitons from organometallic host to organic radical semiconductors Deep Learning-Assisted Spectrum-Structure Correlation: State-of-the-Art and Perspectives World of the Right: Radical Conservatism and Global Order Click-chemistry mediated synthesis of OTBN-1,2,3-Triazole derivatives exhibiting STK33 inhibition with diverse anti-cancer activities Effect Analysis of Nurse-Led Cognitive Behavioural Therapy on Patients with Urinary Incontinence after Radical Prostatectomy Effect Analysis of Nurse-Led Cognitive Behavioural Therapy on Patients with Urinary Incontinence after Radical Prostatectomy Inhibiting spinal cord-specific hsp90 isoforms reveals a novel strategy to improve the therapeutic index of opioid treatment Near-infrared lipid droplets polarity fluorescent probe for early diagnosis of nonalcoholic fatty liver disease Antibiotic discovery with artificial intelligence for the treatment of Acinetobacter baumannii infections A theoretical screening of phytochemical constituents from Millettia brandisiana as inhibitors against acetylcholinesterase Quinolinyl-based multitarget-directed ligands with soluble epoxide hydrolase and fatty acid amide hydrolase inhibitory activities: Synthetic studies and pharmacological evaluations Bioinspired Colorimetric Double Inverse Opal Photonic Crystal Indicators for Ethanol Concentration Sensing in Fermentation Engineering α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies Structure-Based Optimization of Selective and Brain Penetrant CK1δ Inhibitors for the Treatment of Circadian Disruptions Preparation of Pueraria lobata Root-Derived Exosome-Like Nanovesicles and Evaluation of Their Effects on Mitigating Alcoholic Intoxication and Promoting Alcohol Metabolism in Mice Artificial intelligence for high content imaging in drug discovery Yeast Platforms for Production and Screening of Bioactive Derivatives of Rauwolscine
Evidence Blueprint
Discovery of New Phenyltetrazolium Derivatives as Ferroptosis Inhibitors for Treating Ischemic Stroke: An Example Development from Free Radical Scavengers
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
☊ AI-Driven Related Evidence Nodes
(recent articles with at least 5 words in title)
More Evidence
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
Discovery of New Phenyltetrazolium Derivatives as Ferroptosis Inhibitors for Treating Ischemic Stroke: An Example Development from Free Radical Scavengers
🌐 365 Days
AI Virtual Reality Related Evidence Matrix
Discovery of 3-((4-Benzylpyridin-2-yl)amino)benzamides as Potent GPR52 G Protein-Biased Agonists Development of First-in-Class Dual Sirt2/HDAC6 Inhibitors as Molecular Tools for Dual Inhibition of Tubulin Deacetylation Discovery of Potent Multikinase Type-II Inhibitors Targeting CDK5 in the DFG-out Inactive State with Promising Potential against Glioblastoma Ferroptosis in health and disease Discovery of Orally Available and Brain Penetrant AEP Inhibitors Discovery and Characterization of RGH-122, a Potent, Selective, and Orally Bioavailable V1a Receptor Antagonist Pacidusin B isolated from Phyllanthus acidus triggers ferroptotic cell death in HT1080 cells Butylated Hydroxytoluene (BHT) Protects SH-SY5Y Neuroblastoma Cells from Ferroptotic Cell Death: Insights from In Vitro and In Vivo Studies Identification of hyperoxidized PRDX3 as a ferroptosis marker reveals ferroptotic damage in chronic liver diseases Liraglutide attenuates type 2 diabetes mellitus-associated non-alcoholic fatty liver disease by activating AMPK/ACC signaling and inhibiting ferroptosis Structure-Based Drug Design of ADRA2A Antagonists Derived from Yohimbine A "Ferroptosis-Amplifier" Hydrogel for Eliminating Refractory Cancer Stem Cells Post-lumpectomy Peroxynitrite-Triggered Carbon Monoxide Donor Improves Ischemic Stroke Outcome by Inhibiting Neuronal Apoptosis and Ferroptosis Effect and Mechanism of LIN28 on Ferroptosis in Mg2+-free Rat Hippocampal Neuron Model of Epilepsy Brusatol induces ferroptosis to inhibit hepatocellular carcinoma progression by targeting ATF3 Ferroptosis inhibitors reduce celastrol toxicity and preserve its insulin sensitizing effects in insulin resistant HepG2 cells Fatty acid-binding protein 5 is a functional biomarker and indicator of ferroptosis in cerebral hypoxia Structure-Activity Studies of 1,2,4-Oxadiazoles for the Inhibition of the NAD+-Dependent Lysine Deacylase Sirtuin 2 Structure-Activity Studies of 1,2,4-Oxadiazoles for the Inhibition of the NAD+-Dependent Lysine Deacylase Sirtuin 2 Neutral polysaccharide from Gastrodia elata alleviates cerebral ischemia-reperfusion injury by inhibiting ferroptosis-mediated neuroinflammation via the NRF2/HO-1 signaling pathway Ferroptosis in organ ischemia-reperfusion injuries: recent advancements and strategies Ferroptosis contributes to ethanol-induced hepatic cell death via labile iron accumulation and GPx4 inactivation Identification of Novel, Selective Ataxia-Telangiectasia Mutated Kinase Inhibitors with the Ability to Penetrate the Blood-Brain Barrier: The Discovery of AZD1390 Discovery of a First-in-Class CD38 Inhibitor for the Treatment of Mitochondrial Myopathy Ethanol-Induced Hepatic Ferroptosis Is Mediated by PERK-Dependent MAMs Formation: Preventive Role of Quercetin Discovery of a Highly Potent and Selective BRD9 PROTAC Degrader Based on E3 Binder Investigation for the Treatment of Hematological Tumors The Flavonoid Glycoside from Abrus cantoniensis Hance Alleviates Alcoholic Liver Injury by Inhibiting Ferroptosis in an AMPK-Dependent Manner Novel Inhibitory Site Revealed by XAP044 Mode of Action on the Metabotropic Glutamate 7 Receptor Venus Flytrap Domain A guideline on the molecular ecosystem regulating ferroptosis Is Target-Based Drug Discovery Efficient? Discovery and "Off-Target" Mechanisms of All Drugs Melatonin Ameliorates Hepatic Ferroptosis in NAFLD by Inhibiting ER Stress via the MT2/cAMP/PKA/IRE1 Signaling Pathway Selective autophagy associated with iron overload aggravates non-alcoholic steatohepatitis via ferroptosis Iron metabolism and ferroptosis in Non-alcoholic fatty liver disease: what is our next step? In Silico Discovery and Subsequent Characterization of Potent 4R-Tauopathy Positron Emission Tomography Radiotracers Organic Selenium induces ferroptosis in pancreatic cancer cells Research progress on the mechanism of action of heme oxygenase-1 regulating ferroptosis in non-alcoholic fatty liver disease Bioinformatics analysis of ferroptosis-related genes and immune cell infiltration in non-alcoholic fatty liver disease MUC1-C is a target of salinomycin in inducing ferroptosis of cancer stem cells Iron chelation prevents nigrostriatal neurodegeneration in a chronic methamphetamine mice model Melatonin targets ferroptosis through bimodal alteration of redox environment and cellular pathways in NAFLD model Exploring the anti-ferroptosis mechanism of Kai-Xin-San against Alzheimer's disease through integrating network pharmacology, bioinformatics, and experimental validation strategy in vivo and in vitro Discovery of Nivasorexant (ACT-539313): The First Selective Orexin-1 Receptor Antagonist (SO1RA) Investigated in Clinical Trials Discovery of Nivasorexant (ACT-539313): The First Selective Orexin-1 Receptor Antagonist (SO1RA) Investigated in Clinical Trials Pharmacological and Physicochemical Properties Optimization for Dual-Target Dopamine D3 (D3R) and μ-Opioid (MOR) Receptor Ligands as Potentially Safer Analgesics Design of Cell-Permeable Inhibitors of Eukaryotic Translation Initiation Factor 4E (eIF4E) for Inhibiting Aberrant Cap-Dependent Translation in Cancer Design and optimization of selective and potent CDK9 inhibitors with flavonoid scaffold for the treatment of acute myeloid leukemia Elevated levels of alcohol dehydrogenase aggravate ethanol-evoked cardiac remodeling and contractile anomalies through FKBP5-yap-mediated regulation of ferroptosis and ER stress Cell-cell contacts prevent t-BuOOH-triggered ferroptosis and cellular damage in vitro by regulation of intracellular calcium Discovery of Novel Oleamide Analogues as Brain-Penetrant Positive Allosteric Serotonin 5-HT2C Receptor and Dual 5-HT2C/5-HT2A Receptor Modulators Electroacupuncture pretreatment inhibits ferroptosis and inflammation after middle cerebral artery occlusion in rats by activating Nrf2 Discovery of a quinoline-containing compound JT21-25 as a potent and selective inhibitor of apoptosis signal-regulating kinase 1 (ASK1) Fentanyl-Type Antagonist of the μ-Opioid Receptor: Important Role of Axial Chirality in the Active Conformation Metformin alleviates hepatic iron overload and ferroptosis through AMPK-ferroportin pathway in HFD-induced NAFLD DMT1 ubiquitination by Nedd4 protects against ferroptosis after intracerebral hemorrhage Sestrin2 attenuates depressive-like behaviors and neuroinflammation in CUMS mice through inhibiting ferroptosis Berberine ameliorates iron levels and ferroptosis in the brain of 3 × Tg-AD mice Evolutionary Multiobjective Molecule Optimization in an Implicit Chemical Space Evolutionary Multiobjective Molecule Optimization in an Implicit Chemical Space In vitro CRISPR screening uncovers CRTC3 as a regulator of IFN-γ-induced ferroptosis of hepatocellular carcinoma Pyrazoline Derivatives as Promising MAO-A Targeting Antidepressants: An Update Electroacupuncture Inhibits Neural Ferroptosis in Rat Model of Traumatic Brain Injury via Activating System Xc-/GSH/GPX4 Axis Research progress on ferroptosis in gliomas (Review) Benzofurans as acetylcholinesterase inhibitors for treating Alzheimer's disease: synthesis, in vitro testing, and in silico analysis All-Hydrocarbon Stapled Peptide Multifunctional Agonists at Opioid and Neuropeptide FF Receptors: Highly Potent, Long-Lasting Brain Permeant Analgesics with Diminished Side Effects