Development of CDK2 and CDK5 Dual Degrader TMX-2172 was written by Teng, Mingxing;Jiang, Jie;He, Zhixiang;Kwiatkowski, Nicholas P.;Donovan, Katherine A.;Mills, Caitlin E.;Victor, Chiara;Hatcher, John M.;Fischer, Eric S.;Sorger, Peter K.;Zhang, Tinghu;Gray, Nathanael S.. And the article was included in Angewandte Chemie, International Edition in 2020.Name: 4-Amino-3-methylbenzenesulfonamide This article mentions the following:
Cyclin-dependent kinase 2 (CDK2) is a potential therapeutic target for the treatment of cancer. Development of CDK2 inhibitors has been extremely challenging as its ATP-binding site shares high similarity with CDK1, a related kinase whose inhibition causes toxic effects. Here, we report the development of TMX-2172(I), a heterobifunctional CDK2 degrader with degradation selectivity for CDK2 and CDK5 over not only CDK1, but transcriptional CDKs (CDK7 and CDK9) and cell cycle CDKs (CDK4 and CDK6) as well. In addition, we demonstrate that antiproliferative activity in ovarian cancer cells (OVCAR8) depends on CDK2 degradation and correlates with high expression of cyclin E1 (CCNE1), which functions as a regulatory subunit of CDK2. Collectively, our work provides evidence that TMX-2172 represents a lead for further development and that CDK2 degradation is a potentially valuable therapeutic strategy in ovarian and other cancers that overexpress CCNE1. In the experiment, the researchers used many compounds, for example, 4-Amino-3-methylbenzenesulfonamide (cas: 53297-70-4Name: 4-Amino-3-methylbenzenesulfonamide).
4-Amino-3-methylbenzenesulfonamide (cas: 53297-70-4) belongs to amides. Amides include many other important biological compounds, as well as many drugs like paracetamol, penicillin and LSD. Low-molecular-weight amides, such as dimethylformamide, are common solvents. 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.Name: 4-Amino-3-methylbenzenesulfonamide
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