Compositions and methods of modulating S-nitrosylation
A method of treating cardiovascular disorders and diseases in a subject in need thereof includes administering to the subject an ADH inhibitor, AKR inhibitor, and/or SNO-CoAR inhibitor at an amount(s) effective to promote S-nitrosylation of proteins in the subject, wherein the ADH inhibitor and/or SNO-CoAR inhibitor is not an ADH3 inhibitor.
1. A method of treating myocardial ischemia reperfusion injury in a subject in need thereof, the method comprising:
administering to the subject an AKR1A1 inhibitor at an amount effective to promote S-nitrosylation of proteins in the subject and treat myocardial ischemia reperfusion injury in the subject, wherein the AKR1A1 inhibitor has an AKR1A1 IC 50 ≤100 nm, wherein the AKR1A1 inhibitor is imirestat
or an imirestat analogue compound selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
2. The method of claim 1 , wherein a selective or partially selective AKR1A1 inhibitor is administered in combination with a selective or partially selective AKR1B1 inhibitor.
3. The method of claim 2 , wherein the AKR1B1 inhibitor can have a selectivity for AKR1B1 versus AKR1A1≥2 times.
4. A method of treating myocardial ischemia reperfusion injury in a subject in need thereof, the method comprising:
administering to the subject an AKR1A1 inhibitor at an amount effective to promote S-nitrosylation of proteins in the subject and treat myocardial ischemia reperfusion injury in the subject, wherein the AKR1A1 inhibitor has an AKR1A1 IC 50 ≤100 nm, wherein the AKR1A1 inhibitor is an imirestat analogue compound selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
5. A method of treating myocardial ischemia reperfusion injury in a subject in need thereof, the method consisting of:
administering to the subject an AKR1A1 inhibitor at an amount effective to promote S-nitrosylation of proteins in the subject and treat myocardial ischemia reperfusion injury in the subject, wherein the AKR1A1 inhibitor has an AKR1A1 IC 50 ≤100 nm, wherein the AKR1A1 inhibitor is imirestat
or an imirestat analogue compound selected from the group consisting of:
and pharmaceutically acceptable salts thereof.