Rare diseases and pyruvate kinase M2: a promising therapeutic connection.

Pyruvate kinase M2 (PKM2) is a key glycolytic enzyme that regulates proliferating cell metabolism. The role of PKM2 in common diseases has been well established, but its role in rare diseases (RDs) is less understood. Over the past few years, PKM2 has emerged as a crucial player in RDs, including, neoplastic, respiratory, metabolic, and neurological disorders. Herein, we summarize recent findings and developments highlighting PKM2 as an emerging key player in RDs. We also discuss the current status of PKM2 modulation in RDs with particular emphasis on preclinical and clinical studies in addition to current challenges in the field.

Imidazopyrimidine: from a relatively exotic scaffold to an evolving structural motif in drug discovery.

Nitrogen-fused heterocycles are of immense importance in modern drug discovery and development. Among them, imidazopyrimidine is a highly versatile scaffold with vast pharmacological utility. These compounds demonstrate a broad spectrum of pharmacological actions, including antiviral, antifungal, anti-inflammatory, and anticancer. Their adaptable structure allows for extensive structural modifications, which can be utilized for optimizing pharmacological effects via structure-activity relationship (SAR) studies. Additionally, imidazopyrimidine derivatives are particularly noteworthy for their ability to target specific molecular entities, such as protein kinases, which are crucial components of various cellular signaling pathways associated with multiple diseases. Despite the evident importance of imidazopyrimidines in drug discovery, there is a notable lack of a comprehensive review that outlines their role in this field. This review highlights the ongoing interest and investment in exploring the therapeutic potential of imidazopyrimidine compounds, underscoring their pivotal role in shaping the future of drug discovery and clinical medicine.