National Heart, Lung, and Blood Institute 1R61HL179722-01A1

Small molecule therapeutics for heart failure through a reduction in the activity of tristetraprolin and improving cardiac metabolism.

NIH grant awarded to University of Arizona for developing small molecule therapeutics targeting TTP protein to treat heart failure by improving cardiac metabolism and reducing inflammation. The project involves compound optimization and testing in animal models.

Description

This project aims to develop small molecule drugs that inhibit the activity of the TTP protein to improve cardiac metabolism and treat heart failure, while avoiding systemic inflammation. Tristetraprolin (TTP) is a zinc finger protein involved in mRNA decay, affecting inflammatory responses and cardiac metabolism. The project focuses on disrupting TTP's interaction with CNOT1 to inhibit its activity without causing inflammation. Using structural modeling and assays, candidate compounds will be optimized for efficacy and safety in mouse models. Key objectives include optimizing IC50 of lead compounds, assessing effects on TNFα and TTP targets, and evaluating toxicity and therapeutic effects in animal models.

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