《Target Discovery of Selective Non-Small-Cell Lung Cancer Toxins Reveals Inhibitors of Mitochondrial Complex I》 was written by Madhusudhan, Nikhil; Hu, Bin; Mishra, Prashant; Calva-Moreno, Jose F.; Patel, Khushbu; Boriack, Richard; Ready, Joseph M.; Nijhawan, Deepak. Application of 301673-14-3 And the article was included in ACS Chemical Biology in 2020. The article conveys some information:
Selective toxicity among cancer cells of the same lineage is a hallmark of targeted therapies. As such, identifying compounds that impair proliferation of a subset of non-small-cell lung cancer (NSCLC) cell lines represents one strategy to discover new drugs for lung cancer. Previously, phenotypic screens of 202 103 compounds led to the identification of 208 selective NSCLC toxins. The mechanism of action for the majority of these compounds remains unknown. Here, we discovered the target for a series of quinazoline diones (QDC) that demonstrate selective toxicity among 96 NSCLC lines. Using photoreactive probes, we found that the QDC binds to both mitochondrial complex I of the electron transport chain and hydroxyacyl CoA dehydrogenase subunit alpha (HADHA), which catalyzes long-chain fatty acid oxidation Inhibition of complex I is the on-target activity for QDC, while binding to HADHA is off-target. The sensitivity profile of the QDC across NSCLC lines correlated with the sensitivity profiles of six addnl. structurally distinct compounds The antiproliferative activity of these compounds is also the consequence of binding to mitochondrial complex I, reflecting significant structural diversity among complex I inhibitors. Small mols. targeting complex I are currently in clin. development for the treatment of cancer. Our results highlight complex I as a target in NSCLC and report structurally diverse scaffolds that inhibit complex I. After reading the article, we found that the author used tert-Butyl 4-iodopiperidine-1-carboxylate(cas: 301673-14-3Application of 301673-14-3)
tert-Butyl 4-iodopiperidine-1-carboxylate(cas: 301673-14-3) is one of organic iodides. The carbon-iodine bond is weaker than other carbon-halogen bonds due to the poor electronegative nature of the iodine atom. In general, organic iodides are light-sensitive and turn yellow during storage, owing to the formation of iodine. Organic iodides can be alkyl, alkenyl, or alkynyl, and all of them are very reactive toward with many kinds of nucleophiles.Application of 301673-14-3
Referemce:
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com