Xu, Xi published the artcileDiscovery of novel glutaminase 1 allosteric inhibitor with 4-piperidinamine linker and aromatic heterocycles, COA of Formula: C10H20N2O2, the main research area is piperidinamine linker aromatic heterocycle preparation design GLS1 glutaminase inhibitor; glutaminase GLS1 allosteric inhibitor SAR metabolic stability antitumor; 4-Piperidinamine; Allosteric inhibitors; GLS1; Glutaminase 1; Glutamine metabolism.
Glutaminase 1 (GLS1) is overexpressed in multiple types of malignant tumors and is viewed as a promising target in cancer therapy. Thus, the discovery for small-mol. GLS1 inhibitors is urgent. Based on the authors’ previous study of compound I, a potent GLS1 allosteric inhibitor yet with a limited metabolic stability, a structure-based optimization was carried out, with a series of novel GLS1 allosteric inhibitors rationally designed, synthesized and biol. evaluated. Such endeavor has culminated in the identification of compound II, a promising GLS1 allosteric inhibitor with a 4-piperidinamine linker and aromatic heterocycles. Compound II displayed robust GLS1 binding affinity, superior liver microsome metabolic stability, and moderate anti-tumor activity (TGI: 47.5%) in HCT116 xenograft model with no considerable toxicity in vivo. The mechanism underlying the anti-proliferative effect of compound II on HCT116 cells was studied, revealing that the compound blocked the glutamine metabolism, induced the production of ROS, and triggered apoptosis. These findings merit further investigation of compound II as a targeted cancer therapeutic.
European Journal of Medicinal Chemistry published new progress about Allosteric modulators. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, COA of Formula: C10H20N2O2.
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem