Recent development of ATR inhibitors for cancer therapy

Area of Science:

• Oncology
• Molecular Biology
• Medicinal Chemistry

Background:

• Ataxia Telangiectasia and Rad3-related (ATR) kinase is crucial for genomic stability and DNA damage response.
• ATR signaling dysregulation is linked to cancer development, therapeutic resistance, and neurodegenerative diseases.
• ATR inhibitors are promising cancer therapeutics, with several candidates in clinical trials.

Purpose of the Study:

• To review medicinal chemistry progress in ATR inhibitor development since 2018.
• To systematically analyze major chemical scaffolds used in ATR inhibitor design.
• To provide guidance for developing next-generation ATR inhibitors with improved clinical profiles.

Main Methods:

• Literature review focusing on medicinal chemistry advancements in ATR inhibitor development post-2018.
• Systematic analysis of chemical scaffolds and structure-activity relationships.
• Synthesis of information on ongoing clinical trials and candidate molecules like berzosertib, ceralasertib, and gartisertib.

Main Results:

• Significant progress has been made in the medicinal chemistry of ATR inhibitors since 2018.
• Various chemical scaffolds have been explored, leading to potent and selective compounds.
• Berzosertib, ceralasertib, and gartisertib are key examples of ATR inhibitors advancing in clinical trials.

Conclusions:

• Continued medicinal chemistry efforts are essential for developing effective ATR inhibitors.
• Understanding chemical scaffolds is key to designing next-generation inhibitors with enhanced potency and selectivity.
• Optimized ATR inhibitors hold significant potential for improving cancer therapy outcomes.