Uses
AZD 0156 is an inhibitor of the Ataxia-Telangiectasia Mutated (ATM) protein, a signaling kinase involved in the DNA damage response.
Biological Activity
azd0156 is an atm kinase inhibitor.ataxia telangiectasia mutant (atm), a serine/threonine protein kinase from the phosphatidylinositol 3-kinase-related kinase (pikk) family of protein kinases, plays a critical role in the cellular dna damage response signalling activated by dna double strand breaks. activated atm can promote dna repair and s/g1-cell cycle checkpoints to prevent premature mitosis, maintain genomic integrity as well as promote appropriate cell survival or death pathways. thus, atm inhibitor can represent a promosing clinical opportunity to hyper-sensitize tumors to chemo/radiotherapy.
in vitro
azd0156 was identified as a first in class orally available atm inhibitor, showing sub-nanomolar potency in cell based assays of atm inhibition. moreover, azd0156 had selectivities of greater than 1000 fold over other members of the pikk family enzymes [1].
in vivo
in animal study, azd0156 displayed excellent preclinical pk properties including oral bioavailability. additionally, in mouse xenograft models, azd0156 showed robust efficacy after oral administration when combined with double strand breaks (dsb) inducing agents [1].
References
[1] kurt g. pike. identifying high quality, potent and selective inhibitors of atm kinase: discovery of azd0156. [abstract]. in: proceedings of the 107th annual meeting of the american association for cancer research; 2016 apr 16-20; new orleans, la. philadelphia (pa): aacr; cancer res 2016;76(14 suppl):abstract nr 4859.
[2] https://clinicaltrials. gov/ct2/show/nct02588105 term=azd0156&rank=1
