2 research outputs found
Probing the Binding Site of Abl Tyrosine Kinase Using in Situ Click Chemistry
Modern combinatorial chemistry is used to discover compounds
with
desired function by an alternative strategy, in which the biological
target is directly involved in the choice of ligands assembled from
a pool of smaller fragments. Herein, we present the first experimental
result where the use of in situ click chemistry has been successfully
applied to probe the ligand-binding site of Abl and the ability of
this enzyme to form its inhibitor. Docking studies show that Abl is
able to allow the in situ click chemistry between specific azide and
alkyne fragments by binding to Abl-active sites. This report allows
medicinal chemists to use protein-directed in situ click chemistry
for exploring the conformational space of a ligand-binding pocket
and the ability of the protein to guide its inhibitor. This approach
can be a novel, valuable tool to guide drug design synthesis in the
field of tyrosine kinases
Heteronanoparticles by Self-Assembly of Ecdysteroid and Doxorubicin Conjugates To Overcome Cancer Resistance
Heteronanoparticles
(H-NPs) consisting of conjugates characterized
by a squalene tail linked to doxorubicin and ecdysteroid derivatives
are presented. Biological evaluation on A2780ADR cell line confirms
not only the maintenance of the activity of the parental drug but
also the ability to overcome cancer resistance. The <i>in vitro</i> cell uptake was demonstrated, and the involvement of an endosomal-mediated
pathway was suggested