Synthetic Route of 22013-33-8, New Advances in Chemical Research in 2021. Redox catalysis has been broadly utilized in electrochemical synthesis due to its kinetic advantages over direct electrolysis. 22013-33-8, Name is 2,3-Dihydrobenzo[b][1,4]dioxin-6-amine. In a Article, once mentioned of 22013-33-8.
Many natural products that show therapeutic activities are often difficult to synthesize or isolate and have unknown targets, hindering their development as drugs. Identifying druggable hotspots targeted by covalently acting anti-cancer natural products can enable pharmacological interrogation of these sites with more synthetically tractable compounds. Here, we used chemoproteomic platforms to discover that the anti-cancer natural product withaferin A targets C377 on the regulatory subunit PPP2R1A of the tumor-suppressor protein phosphatase 2A (PP2A) complex leading to activation of PP2A activity, inactivation of AKT, and impaired breast cancer cell proliferation. We developed a more synthetically tractable cysteine-reactive covalent ligand, JNS 1-40, that selectively targets C377 of PPP2R1A to impair breast cancer signaling, proliferation, and in vivo tumor growth. Our study highlights the utility of using chemoproteomics to map druggable hotspots targeted by complex natural products and subsequently interrogating these sites with more synthetically tractable covalent ligands for cancer therapy. Many natural products exhibit therapeutic activity, but translating these molecules into drugs is hindered by difficulty in their synthesis and isolation. Grossman, Ward et al. show that chemoproteomic technologies can be used to discover simpler molecules that react with the same sites as those targeted by natural products.
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