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Description: BI-9627 is a novel and highly potent NHE1 (sodium-hydrogen exchanger isoform 1) inhibitor with with an EC50 of 31 nM. It has good drug like properties such as high oral bioavailability, low DDI (drug drug interaction) potential, excellent pharmacokinetics, and good selectivity against NHE2 and NHE3. Sodium-hydrogen exchanger isoform 1 (NHE1) is a ubiquitously expressed transmembrane ion channel responsible for intracellular pH regulation. During myocardial ischemia, low pH activates NHE1 and causes increased intracellular calcium levels and aberrant cellular processes, leading to myocardial stunning, arrhythmias, and ultimately cell damage and death. The role of NHE1 in cardiac injury has prompted interest in the development of NHE1 inhibitors for the treatment of heart failure.
References: J Med Chem. 2012 Aug 23; 55(16):7114-40.
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