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Updated: Sep 11, 2025

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
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Development of quinazoline based ATR inhibitors as targeted therapeutics for ATM-deficient and ATM-proficient cancers

Pranav U Bhagwat1, Sivapriya Kirubakaran1

  • 1Department of Chemistry, Indian Institute of Technology Gandhinagar, Palaj, Gandhinagar, Gujarat, 382055, India. priyak@iitgn.ac.in.

Organic & Biomolecular Chemistry
|August 11, 2025
PubMed

Insights

Researchers developed a novel quinazoline-based inhibitor targeting Ataxia telangiectasia and rad3-related (ATR) kinase for cancer therapy. This new compound shows promising efficacy and reduced toxicity, making it a potential pre-clinical candidate.

Area of Science:

  • Oncology
  • Medicinal Chemistry
  • Molecular Biology

Background:

  • Ataxia telangiectasia and rad3-related (ATR) kinase is a key regulator of the DNA replication stress response.
  • ATR kinase is a promising therapeutic target for various cancers.
  • Current ATR kinase inhibitors face challenges due to patient toxicity.

Purpose of the Study:

  • To develop a novel quinazoline-based ATR inhibitor with improved efficacy and reduced toxicity.
  • To synthesize and optimize a library of quinazoline derivatives.
  • To evaluate the anti-cancer activity and safety profile of the lead compound.

Main Methods:

  • Scaffold hopping technique was employed to design novel compounds.
  • A library of quinazoline-based compounds was synthesized.
  • In vitro assays were performed to assess anti-cancer activity in ATM-deficient and ATM-proficient cell lines, as well as toxicity in non-cancerous cells.

Main Results:

  • A novel quinazoline-based ATR inhibitor, compound 11, was identified and optimized.
  • Compound 11 demonstrated promising anti-cancer activity in both ATM-deficient and ATM-proficient cancer cell lines.
  • Compound 11 exhibited significant non-toxicity in non-cancerous cell lines, suggesting a favorable safety profile.

Conclusions:

  • The novel quinazoline-based compound 11 is a potent ATR inhibitor with a promising therapeutic window.
  • Compound 11 warrants further investigation as a pre-clinical candidate for cancer treatment.
  • This study highlights the potential of scaffold hopping in developing targeted cancer therapies with reduced toxicity.

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