Discovery of a New Isoxazole-3-hydroxamate-Based Histone Deacetylase 6 Inhibitor SS-208 with Antitumor Activity in Syngeneic Melanoma Mouse Models was written by Shen, Sida;Hadley, Melissa;Ustinova, Kseniya;Pavlicek, Jiri;Knox, Tessa;Noonepalle, Satish;Tavares, Mauricio T.;Zimprich, Chad A.;Zhang, Guiping;Robers, Matthew B.;Barinka, Cyril;Kozikowski, Alan P.;Villagra, Alejandro. And the article was included in Journal of Medicinal Chemistry in 2019.SDS of cas: 2670-38-4 This article mentions the following:
Isoxazole is a five-membered heterocycle that is widely used in drug discovery endeavors. Here, the authors report the design, synthesis, and structural and biol. characterization of SS-208, a novel HDAC6-selective inhibitor containing the isoxazole-3-hydroxamate moiety as a zinc-binding group as well as a hydrophobic linker. A crystal structure of the Danio rerio HDAC6/SS-208 complex reveals a bidentate coordination of the active-site zinc ion that differs from the preferred monodentate coordination observed for HDAC6 complexes with phenylhydroxamate-based inhibitors. While SS-208 has minimal effects on the viability of murine SM1 melanoma cells in vitro, it significantly reduced in vivo tumor growth in a murine SM1 syngeneic melanoma mouse model. These findings suggest that the antitumor activity of SS-208 is mainly mediated by immune-related antitumor activity as evidenced by the increased infiltration of CD8+ and NK+ T cells and the enhanced ratio of M1 and M2 macrophages in the tumor microenvironment. In the experiment, the researchers used many compounds, for example, 3,4-Dichlorobenzamide (cas: 2670-38-4SDS of cas: 2670-38-4).
3,4-Dichlorobenzamide (cas: 2670-38-4) belongs to amides. The amide group is called a peptide bond when it is part of the main chain of a protein, and an isopeptide bond when it occurs in a side chain, such as in the amino acids asparagine and glutamine. In simple aromatic amides, fragmentation occurs on both sides of the carbonyl group. If a hydrogen is available in N-substituted aromatic amides, it tends to migrate and form an aromatic amine and the loss of a ketene.SDS of cas: 2670-38-4
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics