The Nicotinic Acetylcholine Receptor is an Allosteric Protein; The Specific Allosteric Model does not apply to the Receptor's Molecular Mechanism of Action

1987 ◽  
pp. 51-62
Keyword(s):  
Molecular Mechanism ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Mechanism Of Action ◽  
Nicotinic Acetylcholine ◽  
Molecular Mechanism Of Action ◽  
Allosteric Model ◽  
Allosteric Protein

Diacylfuroxans Are Masked Nitrile Oxides That Inhibit GPX4 Covalently

2019 ◽  
Author(s):  
John Eaton ◽  
Richard A. Ruberto ◽  
Anneke Kramm ◽  
Vasanthi S. Viswanathan ◽  
Stuart Schreiber
Keyword(s):  
Molecular Mechanism ◽  
Mechanism Of Action ◽  
Therapeutic Target ◽  
Biologically Active ◽  
Drug Resistant ◽  
Nitrile Oxides ◽  
Molecular Mechanism Of Action

<div><div><div><p>GPX4 represents a promising yet difficult-to-drug therapeutic target for the treatment of, among others, drug-resistant cancers. While most GPX4 inhibitors rely on a chloroacetamide moiety to modify covalently the protein’s catalytic selenocysteine residue, the discovery and mechanistic elucidation of structurally diverse GPX4-inhibiting molecules has uncovered novel electrophilic warheads that bind and inhibit GPX4. Here we report our discovery that diacylfuroxans can act as masked nitrile oxides that inhibit GPX4 covalently. These observations illuminate a novel molecular mechanism of action for biologically active furoxans and also suggest that nitrile oxides may be uniquely suited to targeting GPX4.</p></div></div></div>

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