The current study reports novel inhibitors of s-nitrosoglutathione reductase (GSNOR) identified that specifically inhibit GSNOR among the alcohol dehydrogenases. These inhibitors may bind into the GSNO binding site and inhibit GSNOR at multiple places in its kinetic pathway. These molecules inhibit GSNOR in a dose dependent manner and demonstrate that GSNOR actively regulates the s-nitrosylation of proteins against incoming low molecular weight nitrosothiols. These compounds are useful in method of treatment of diseases such as asthma, chronic obstructive pulmonary disease, heart disease, heart failure, heart attack, hypertension, atherosclerosis, restenosis, impotence, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, stroke, septic shock, cardiogenic shock, endotoxic shock, toxic shock syndrome, systemic inflammatory response syndrome, and other inflammatory diseases. These compounds can also be used to diagnose and/or study disease and/or conditions or enzymes involving the s-nitrosylation of proteins.

Sanghani; Paresh

Indiana University Research and Technology Corporation

Materials and methods for inhibiting mamalian S-nitrosoglutathione reductase

The invention provides compounds and methods of their use in the detection of apoptosis and necrosis both in vitro and in vivo. Also provided are compounds and methods of their use in selective delivery of agents to cells undergoing apoptosis or necrosis. The compounds and methods are based on conjugates formed with a dehydrogenase such as lactate dehydrogenase, alcohol dehydrogenase, aldehyde dehydrogenase, and malate dehydrogenase. The compounds and methods are useful in the diagnosis and treatment of conditions characterized by apoptosis, including cancer, cardiac disease, neurologic disease including stroke, and autoimmunity. The compounds and methods offer distinct advantages over corresponding compounds and methods based on Annexin V. Also provided are methods for screening for compounds that modulate, i.e., inhibit or promote, apoptosis.

alcohol dehydrogenase/stroke

Materials and methods for inhibiting mamalian S-nitrosoglutathione reductase

Compositions for detecting cell death and methods of use thereof

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