Radiofluorination of a highly potent ATM inhibitor as a potential PET imaging agent

EJNMMI Research

Table 1 ATM inhibitors under preclinical and clinical investigation

Name	ATM IC₅₀ (nM)	Status/Key findings
AZD1390	0.78	Phase I clinical trial for brain cancer in combination with radiotherapy [16] Phase I clinical trial for NSCLC in combination with radiotherapy [17]. Phase I clinical trial completed to assess brain PET imaging with ¹¹C-labelled AZD1390 (labelled in the starred position) [5, 6]
AZD0156	0.58	Phase I clinical trial for advanced solid tumours, alone and in combination with other agents [18, 19]
M4076	0.2	Phase I clinical trial for advanced solid tumours [20, 21]
M3541	0.5	Completed phase I clinical trials for solid tumours in combination with radiotherapy [22]
KU60019	6.3	Preclinical in vitro evaluation of KU60019 in combination with CHK2 inhibitor, CX4945 [23, 24]
KU55933	13	First specific ATM inhibitor, demonstrated sensitisation of cells to ionising radiation and topoisomerase inhibitors [25]
KU59403	3	Preclinical investigation in combination with topoisomerase inhibitors and improved pharmacologic properties over previous KuDOS inhibitors [11]
CP466722	410	Demonstrated rapid and reversible inhibition of ATM in vitro, revealing that only transient ATM inhibition is require for cell sensitisation to ionising radiation [26, 27]