de Jesus Cortez, Felipe; Nguyen, Phuong; Truillet, Charles; Tian, Boxue; Kuchenbecker, Kristopher M.; Evans, Michael J.; Webb, Paul; Jacobson, Matthew P.; Fletterick, Robert J.; England, Pamela M. published their research in ACS Chemical Biology on December 15 ,2017. The article was titled 《Development of 5N-Bicalutamide, a High-Affinity Reversible Covalent Antiandrogen》.SDS of cas: 887707-25-7 The article contains the following contents:
Resistance to clin. antiandrogens has plagued the evolution of effective therapeutics for advanced prostate cancer. As with the first-line therapeutic bicalutamide (Casodex), resistance to newer antiandrogens (enzalutamide, ARN-509) develops quickly in patients, despite the fact that these drugs have ∼10-fold better affinity for androgen receptor than bicalutamide. Improving affinity alone is often not sufficient to prevent resistance and alternative strategies are needed to improve antiandrogen efficacy. Covalent and reversible covalent drugs are being used to thwart drug resistance in other contexts, and activated aryl nitriles are among the moieties being exploited for this purpose. The authors capitalized on the presence of an aryl nitrile in bicalutamide, and the existence of a native cysteine residue (Cys784) in the androgen receptor ligand binding pocket, to develop 5N-bicalutamide I, a cysteine-reactive antiandrogen. I exhibits a 150-fold improvement in Ki and 20-fold improvement in IC50 over the parent compound The authors attribute the marked improvement in affinity and activity to the formation of a covalent adduct with Cys784, a residue that is not among the more than 160 androgen receptor point mutations associated with prostate cancer. Increasing the residence time of bound antiandrogen via formation of a covalent adduct may forestall the drug resistance seen with current clin. antiandrogens. After reading the article, we found that the author used 2-Chloro-5-iodo-3-(trifluoromethyl)pyridine(cas: 887707-25-7SDS of cas: 887707-25-7)
2-Chloro-5-iodo-3-(trifluoromethyl)pyridine(cas: 887707-25-7) belongs to pyridine. Pyridine, its benzo and pyridine-based compounds play diverse roles in organic chemistry. As ligands, solvents, and catalysts they facilitate reactions; thus descriptions of these new ligands and their applications abound each year.SDS of cas: 887707-25-7
Referemce:
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com