We have located links that may give you full text access.
Identification of Cellular Protein Targets of a Half-Sandwich Iridium(III) Complex Reveals Its Dual Mechanism of Action via Both Electrophilic and Oxidative Stresses.
Journal of Medicinal Chemistry 2024 April 6
Identification of intracellular targets of anticancer drug candidates provides key information on their mechanism of action. Exploiting the ability of the anticancer (C∧N)-chelated half-sandwich iridium(III) complexes to covalently bind proteins, click chemistry with a bioorthogonal azido probe was used to localize a phenyloxazoline-chelated iridium complex within cells and profile its interactome at the proteome-wide scale. Proteins involved in protein folding and actin cytoskeleton regulation were identified as high-affinity targets. Upon iridium complex treatment, the folding activity of Heat Shock Protein HSP90 was inhibited in vitro and major cytoskeleton disorganization was observed. A wide array of imaging and biochemical methods validated selected targets and provided a multiscale overview of the effects of this complex on live human cells. We demonstrate that it behaves as a dual agent, inducing both electrophilic and oxidative stresses in cells that account for its cytotoxicity. The proposed methodological workflow can open innovative avenues in metallodrug discovery.
Full text links
Related Resources
Trending Papers
British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults.Gut 2024 April 17
Systemic lupus erythematosus.Lancet 2024 April 18
Should renin-angiotensin system inhibitors be held prior to major surgery?British Journal of Anaesthesia 2024 May
Ventilator Waveforms May Give Clues to Expiratory Muscle Activity.American Journal of Respiratory and Critical Care Medicine 2024 April 25
Acute Kidney Injury and Electrolyte Imbalances Caused by Dapagliflozin Short-Term Use.Pharmaceuticals 2024 March 27
Colorectal polypectomy and endoscopic mucosal resection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2024.Endoscopy 2024 April 27
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app