Targeting the Subpocket Enables the Discovery of Thiadiazole–Pyridazine Derivatives as Glutaminase C Inhibitors
Hanyu Sun,
Tingting Du,
Minjian Yang
et al.
Abstract:As glutaminase C (GAC) has become an attractive target
for cancer
treatment by regulating glutaminolysis, thus, interest in GAC inhibitors
has risen in recent years. Herein, a potential binding subpocket comprising
basic residues was identified, and through extensive structure–activity
relationship studies, promising inhibitors 11 and 39 were identified with robust GAC inhibitory activity and
A549 cell antiproliferative activity. X-ray crystallography of the 11–GAC and 27–GAC complexes revealed
a novel binding… Show more
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