Identification of allosteric inhibitors of the ecto-5'-nucleotidase (CD73) targeting the dimer interface.

ABSTRACT: The ecto-5'-nucleotidase CD73 plays an important role in the production of immune-suppressive adenosine in tumor micro-environment, and has become a validated drug target in oncology. Indeed, the anticancer immune response involves extracellular ATP to block cell proliferation through T-cell activation. However, in the tumor micro-environment, two extracellular membrane-bound enzymes (CD39 and CD73) are overexpressed and hydrolyze efficiently ATP into AMP then further into immune-suppressive adenosine. To circumvent the impact of CD73-generated adenosine, we applied an original bioinformatics approach to identify new allosteric inhibitors targeting the dimerization interface of CD73, which should impair the large dynamic motions required for its enzymatic function. Several hit compounds is

SUBMITTER: Rahimova R 

PROVIDER: S-EPMC5805337 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature