Skip to Content
Merck
  • CD73 inhibition by purine cytotoxic nucleoside analogue-based diphosphonates.

CD73 inhibition by purine cytotoxic nucleoside analogue-based diphosphonates.

European journal of medicinal chemistry (2018-09-04)
Charles Dumontet, Suzanne Peyrottes, Céline Rabeson, Emeline Cros-Perrial, Pierre Yves Géant, Laurent Chaloin, Lars Petter Jordheim
ABSTRACT

The ecto-5'-nucleotidase CD73 has emerged as an important drug target in oncoimmunology as well as in other diseases. We describe new ADP analogues as CD73 inhibitors based on the replacement of the adenosine moiety, in the reference inhibitor APCP, by purine nucleoside analogues. Compounds were assessed for CD73 inhibition both on purified recombinant protein and on CD73-expressing cancer cells. The clofarabine-containing compound (2) was shown to be more potent than APCP with IC50 values of 0.18 μM (vs. 3.8 μM) on purified protein and 0.24 μM (vs. 23.6 μM) on CD73 expressed on cells. This work gives additional insights into structure-activity relationship of substrate-analogues as CD73 inhibitors.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Clofarabine, ≥98% (HPLC)