Medicinal chemistry breakthroughs on ATM, ATR, and DNA-PK inhibitors as prospective cancer therapeutics DOI Creative Commons

Ram Lal Sharma,

Anshul Mishra,

Monika Bhardwaj

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 40(1)

Published: April 21, 2025

This review discusses the critical roles of Ataxia Telangiectasia Mutated Kinase (ATM), ATM and Rad3-related (ATR), DNA-dependent protein kinase (DNA-PK) in DNA damage response (DDR) their implications cancer. Emphasis is placed on intricate interplay between these kinases, highlighting collaborative distinct maintaining genomic integrity promoting tumour development under dysregulated conditions. Furthermore, covers ongoing clinical trials, patent literature, medicinal chemistry campaigns ATM/ATR/DNA-PK inhibitors as antitumor agents. Notably, employed robust drug design strategies aimed at assembling new structural templates with amplified DDR inhibitory ability, well outwitting pharmacokinetic liabilities existing inhibitors. Given success attained through such endeavours, pipeline repair anticipated to be supplemented by a reasonable number tractable entries (DDR inhibitors) soon.

Language: Английский

Medicinal chemistry breakthroughs on ATM, ATR, and DNA-PK inhibitors as prospective cancer therapeutics DOI Creative Commons

Ram Lal Sharma,

Anshul Mishra,

Monika Bhardwaj

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 40(1)

Published: April 21, 2025

This review discusses the critical roles of Ataxia Telangiectasia Mutated Kinase (ATM), ATM and Rad3-related (ATR), DNA-dependent protein kinase (DNA-PK) in DNA damage response (DDR) their implications cancer. Emphasis is placed on intricate interplay between these kinases, highlighting collaborative distinct maintaining genomic integrity promoting tumour development under dysregulated conditions. Furthermore, covers ongoing clinical trials, patent literature, medicinal chemistry campaigns ATM/ATR/DNA-PK inhibitors as antitumor agents. Notably, employed robust drug design strategies aimed at assembling new structural templates with amplified DDR inhibitory ability, well outwitting pharmacokinetic liabilities existing inhibitors. Given success attained through such endeavours, pipeline repair anticipated to be supplemented by a reasonable number tractable entries (DDR inhibitors) soon.

Language: Английский

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