Novel Oxindole Sulfonamides and Sulfamides [electronic resource] : EPZ031686, the First Orally Bioavailable Small Molecule SMYD3 Inhibitor

• Ngôn ngữ: eng
• Ký hiệu phân loại: 547.7 Macromolecules and related compounds
• Thông tin xuất bản: Argonne, Ill. : Oak Ridge, Tenn. : Argonne National Laboratory ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2015
• Mô tả vật lý: Size: p. 134-138 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 261115
• Chủ đề: 1. 60 applied life sciences; 2. Kmt; 3. Methyltransferase; 4. Oncology; 5. Oxindole; 6. Smyd3; 7. Tool compound

Tóm tắt

 SMYD3 has been implicated in a range of cancers
  however, until now no potent selective small molecule inhibitors have been available for target validation studies. A novel oxindole series of SMYD3 inhibitors was identified through screening of the Epizyme proprietary histone methyltransferase-biased library. Potency optimization afforded two tool compounds, sulfonamide EPZ031686 and sulfamide EPZ030456, with cellular potency at a level sufficient to probe the in vitro biology of SMYD3 inhibition. EPZ031686 shows good bioavailability following oral dosing in mice making it a suitable tool for potential in vivo target validation studies.