NCIt definition : A drug-dendrimer conjugate composed of a B-cell lymphoma 2 (Bcl-2)/Bcl-XL inhibitor
AZD4320 that is chemically conjugated to a proprietary 5-generation pegylated poly-lysine
dendrimer via a hydrolytically labile linker, with potential pro-apoptotic and antineoplastic
activities. Upon administration of AZD0466, AZD4320 is released through hydrolytic
cleavage of the linker. AZD4320 is a Bcl2-homology domain 3 (BH3) mimetic that specifically
binds to and inhibits the activity of the anti-apoptotic proteins Bcl-2 and Bcl-XL.
This restores apoptotic processes and inhibits cell proliferation in Bcl-2/Bcl-XL-dependent
tumor cells. Bcl-2 and Bcl-XL, proteins belonging to the Bcl-2 family that are overexpressed
in many cancers, play an important role in the negative regulation of apoptosis. Their
expression in tumors is associated with increased drug resistance and cancer cell
survival. The conjugation of AZD 4320 to the dendrimer construct may allow extended
release of the agent, which may improve efficacy and lower toxicity.;
Semantic type(s)