A positron emission tomography imaging probe selectively targeting the BD1 bromodomain and extra-terminal domain.

ABSTRACT: The two tandem bromodomains of BET (bromodomain and extra-terminal domain) proteins (BD1 and BD2) may play distinct and critical roles in neurological diseases. To better understand the underlying mechanisms of the BD1 bromodomain and facilitate brain permeable domain-selective inhibitor development, we describe here the development of the first BET BD1 positron emission tomography (PET) radioligand [¹¹C]1a. Compound 1a was tested to possess potent binding affinities and good selectivity (>20-fold over BD2) for BD1 bromodomains of BRD2 (K_d = 25 nM), BRD3 (K_d = 24 nM), and BRD4 (K_d = 19 nM). Physicochemical characterization of 1a indicated the brain permeability and specific binding. [¹¹C]1a was radiosynthesized in

SUBMITTER: Bai P 

PROVIDER: S-EPMC9618257 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature