Unraveling the Journey of Alzheimer’s Treatment: Exploring Human Glutaminyl Cyclase Inhibitors

Published on August 3, 2023

Imagine you’re a treasure hunter on a quest to find the ultimate cure for Alzheimer’s disease. Your key to success lies within the elusive human glutaminyl cyclase (hQC), a target that holds the potential to change lives. Like a skilled detective, scientists have been unraveling the secrets of hQC and its involvement in Alzheimer’s pathology. They have discovered a promising weapon called the benzimidazole-based QC inhibitor, PQ912, which has shown early signs of effectiveness while maintaining safety. This breakthrough has brought renewed hope to the fight against AD. In their tireless pursuit, researchers have explored classic Zinc binding group (ZBG)-containing chemicals and identified several potent inhibitors. As they navigate through challenges and new trends in inhibitor development, they are paving the way for an alternative and promising therapy that could modify the course of AD. Join the exploration of this fascinating research to understand how hQC inhibitors may hold the key to unlocking a brighter future for Alzheimer’s patients!

Human glutaminyl cyclase (hQC) is drawing considerable attention and emerging as a potential druggable target for Alzheimer’s disease (AD) due to its close involvement in the pathology of AD via the post-translational pyroglutamate modification of amyloid-β. A recent phase 2a study has shown promising early evidence of efficacy for AD with a competitive benzimidazole-based QC inhibitor, PQ912, which also demonstrated favorable safety profiles. This finding has sparked new hope for the treatment of AD. In this review, we briefly summarize the discovery and evolution of hQC inhibitors, with a particular interest in classic Zinc binding group (ZBG)-containing chemicals reported in recent years. Additionally, we highlight several high-potency inhibitors and discuss new trends and challenges in the development of QC inhibitors as an alternative and promising disease-modifying therapy for AD.

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