Insight into small-molecule inhibitors targeting extracellular nucleotide pyrophosphatase/phosphodiesterase1 for potential multiple human diseases.

Extracellular nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) has been identified as a type II transmembrane glycoprotein. It plays a crucial role in various biological processes, such as bone mineralization, cancer cell proliferation, and immune regulation. Consequently, ENPP1 has garnered attention as a promising target for pharmacological interventions. Despite its potential, the development of clinical-stage ENPP1 inhibitors for solid tumors, diabetes, and silent rickets remains limited. However, there are encouraging findings from preclinical trials involving small molecules exhibiting favorable therapeutic effects and safety profiles. This perspective aims to shed light on the structural properties, biological functions and the relationship between ENPP1 and diseases. Additionally, it focuses on the structure-activity relationship of ENPP1 inhibitors, with the intention of guiding the future development of new and effective ENPP1 inhibitors.

PDE4 inhibitors for disease therapy: advances and future perspective.

The PDE4 enzyme family is specifically responsible for hydrolyzing cAMP and plays a vital role in regulating the balance of second messengers. As a crucial regulator in signal transduction, PDE4 has displayed promising pharmacological targets in a variety of diseases, for which its inhibitors have been used as a therapeutic strategy. This review provides a comprehensive summary of the development of PDE4 inhibitors in the past few years, along with the structure, clinical and research progress of multiple inhibitors of PDE4, focusing on the research and development strategies of PDE4 inhibitors. We hope our analysis will provide a significant reference for the future development of new PDE4 inhibitors.