Summary
The DNA damage repair (DDR) is one of the broadest and most complex cellular responses on external stimuli. In the case of DNA double strand breaks (DSB), a very important upstream signaling agent is ataxia-telangiectasia mutated (ATM) kinase, which directly binds to damaged DNA and plays a key role in the initiation and control of the downstream processes including cell cycle checkpoints, activation of senescence pathways and prevention of mitotic catastrophe.
Due to these critical functions, ATM is considered to be a promising target for the development of novel therapeutic strategies in the treatment of malignancies, where pharmacological inhibition of ATM can be exploited for the sensibilization of cancer cells towards DSB inducing agents.
Via our medicinal chemistry development pipeline we independently evaluated two different scaffolds in parallel to increase the chances of a successful profiling of novel ATM inhibitors with a favorable profile. Both approaches finally lead to the generation of novel IP and the identification of promising candidates in both structural classes.
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