Discovery of novel tertiary amide derivatives as NEDDylation pathway activators to inhibit the tumor progression in vitro and in vivo was written by Fu, Dong-Jun;Song, Jian;Zhu, Ting;Pang, Xiao-Jing;Wang, Sheng-Hui;Zhang, Yan-Bing;Wu, Bo-Wen;Wang, Jun-Wei;Zi, Xiaolin;Zhang, Sai-Yang;Liu, Hong-Min. And the article was included in European Journal of Medicinal Chemistry in 2020.Computed Properties of C8H9Cl This article mentions the following:
NEDDylation pathway regulates multiple physiol. process, unlike inhibitors, NEDDylation activators are rarely studied. Novel amide derivatives were synthesized and evaluated for antiproliferative activity against MGC803, MCF-7 and PC-3 cells. Among them, VII-31 displayed the most potent activity with an IC50 value of 94 nmol/L against MGC803 cells. Cellular mechanisms elucidated that VII-31 inhibited the cell viability, arrested cell cycle at G2/M phase and induced apoptosis via intrinsic and extrinsic pathways against MGC803 cells. In addition, VII-31 activated NAE1-Ubc12-Cullin1 NEDDylation via interacting with NAE1 directly. Furthermore, the activation of NEDDylation resulted in the degradation of inhibitor of apoptosis proteins (IAPs). Importantly, VII-31 inhibited tumor growth in xenograft models in vivo without the apparent toxicity. In summary, it is the first time to reveal that VII-31 deserves consideration for cancer therapy as a NEDDylation activator. In the experiment, the researchers used many compounds, for example, 1-(Chloromethyl)-3-methylbenzene (cas: 620-19-9Computed Properties of C8H9Cl).
1-(Chloromethyl)-3-methylbenzene (cas: 620-19-9) belongs to organic chlorides. Organic chlorides are compounds containing a carbon-chlorine bond, which are widely used in the oil field as a wax dissolver. Aliphatic organochlorides are often alkylating agents as chlorine can act as a leaving group, which can result in cellular damage.Computed Properties of C8H9Cl
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics