Interruption of MDM2 signaling augments MDM2-targeted T cell-based antitumor immunotherapy through antigen-presenting machinery was written by Kono, Michihisa;Kumai, Takumi;Hayashi, Ryusuke;Yamaki, Hidekiyo;Komatsuda, Hiroki;Wakisaka, Risa;Nagato, Toshihiro;Ohkuri, Takayuki;Kosaka, Akemi;Ohara, Kenzo;Kishibe, Kan;Takahara, Miki;Katada, Akihiro;Hayashi, Tatsuya;Celis, Esteban;Kobayashi, Hiroya;Harabuchi, Yasuaki. And the article was included in Cancer Immunology Immunotherapy in 2021.Synthetic Route of C30H30Cl2N4O4 This article mentions the following:
Identification of immunogenic tumor antigens, their corresponding T cell epitopes and the selection of effective adjuvants are prerequisites for developing effective cancer immunotherapies such as therapeutic vaccines. Murine double minute 2 (MDM2) is an E3 ubiquitin-protein ligase that neg. regulates tumor suppressor p53. Because MDM2 overexpression serves as a poor prognosis factor in various types of tumors, it would be beneficial to develop MDM2-targeted cancer vaccines. In this report, we identified an MDM2-derived peptide epitope (MDM232-46) that elicited antigen-specific and tumor-reactive CD4+ T cell responses. These CD4+ T cells directly killed tumor cells via granzyme B. MDM2 is expressed in head and neck cancer patients with poor prognosis, and the T cells that recognize this MDM2 peptide were present in these patients. Notably, Nutlin-3 (MDM2-p53 blocker), inhibited tumor cell proliferation, was shown to augment antitumor T cell responses by increasing MDM2 expression, HLA-class I and HLA-DR through class II transactivator (CIITA). These results suggest that the use of this MDM2 peptide as a therapeutic vaccine combined with MDM2 inhibitors could represent an effective immunol. strategy to treat cancer. 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: 548472-68-0Synthetic Route of C30H30Cl2N4O4).
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. Piperazine belongs to the family of medicines called anthelmintics. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Synthetic Route of C30H30Cl2N4O4
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics