Homo-PROTAC mediated suicide of MDM2 to treat non-small cell lung cancer was written by He, Shipeng;Ma, Junhui;Fang, Yuxin;Liu, Ying;Wu, Shanchao;Dong, Guoqiang;Wang, Wei;Sheng, Chunquan. And the article was included in Acta Pharmaceutica Sinica B in 2021.Product Details of 548472-68-0 This article mentions the following:
The dose-related adverse effects of MDM2-P53 inhibitors have caused significant concern in the development of clin. safe anticancer agents. Herein we report an unprecedented homo-PROTAC strategy for more effective disruption of MDM2-P53 interaction. The design concept is inspired by the capacity of sub-stoichiometric catalytic PROTACs enabling to degrade an unwanted protein and the dual functions of MDM2 as an E3 ubiquitin ligase and a binding protein with tumor suppressor P53. The new homo-PROTACs are designed to induce self-degradation of MDM2. The results of the investigation have shown that PROTAC 11a efficiently dimerizes MDM2 with highly competitive binding activity and induces proteasome-dependent self-degradation of MDM2 in A549 non-small cell lung cancer cells. Furthermore, markedly, enantiomer 11a-1 exhibits potent in vivo antitumor activity in A549 xenograft nude mouse model, which is the first example of homo-PROTAC with in vivo therapeutic potency. This study demonstrates the potential of the homo-PROTAC as an alternative chem. tool for tumorigenic MDM2 knockdown, which could be developed into a safe therapy for cancer treatment. In the experiment, the researchers used many compounds, for example, 4-(cis-4,5-Bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one (cas: 548472-68-0Product Details of 548472-68-0).
4-(cis-4,5-Bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one (cas: 548472-68-0) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Product Details of 548472-68-0
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Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics