TRT Inhibitors

Telomerase reverse transcriptase (TERT) inhibitors represent a class of compounds specifically designed to target and inhibit the enzymatic activity of telomerase reverse transcriptase. Telomerase, an enzyme complex responsible for maintaining the integrity of telomeres in cells, is composed of a protein component and an RNA component. The protein component, known as TERT, is the catalytic subunit of the telomerase complex. Telomeres are repetitive DNA sequences located at the ends of linear chromosomes, acting as protective caps. Over time, as cells divide, telomeres naturally shorten. However, in certain cell types, such as stem cells and some cancer cells, TERT can prevent this shortening by adding repetitive sequences back to the ends of telomeres, granting the cells an ability to divide indefinitely.

TERT inhibitors have been synthesized and studied mainly due to their ability to halt the action of TERT, thereby limiting the elongation of telomeres. The inhibition of TERT has profound implications on cellular lifespan and proliferation. From a chemical perspective, these inhibitors often possess unique structural motifs that allow them to effectively interact with and inhibit the TERT protein. These structural motifs are often found in extensive structure-activity relationship (SAR) studies, in which various modifications to a molecule are made to understand which features are most critical for inhibitory activity. As such, the design of TERT inhibitors is a sophisticated interplay between organic synthesis, molecular biology, and biophysical studies, aiming to achieve selectivity and potency in the inhibition of the target enzyme.