XINTONG LIU1,2,3, EMIKO SANADA1,3,4, JIANG LI5, XIAOMENG LI6, HIROYUKI OSADA1,4,7,*, NOBUMOTO WATANABE1,2,3,*
Oncology Research, Vol.31, No.5, pp. 645-654, 2023, DOI:10.32604/or.2023.030240
Abstract β-transducin repeat-containing protein (β-TrCP) is an F-box protein subunit of the E3 Skp1-Cullin-F box (SCF) type ubiquitin-ligase complex, and provides the substrate specificity for the ligase. To find potent ligands of β-TrCP useful for the proteolysis targeting chimera (PROTAC) system using β-TrCP in the future, we developed a high-throughput screening system for small molecule β-TrCP ligands. We screened the chemical library utilizing the system and obtained several hit compounds. The effects of the hit compounds on in vitro ubiquitination activity of SCFβ-TrCP1 and on downstream signaling pathways were examined. Hit compounds NPD5943, NPL62020-01, and NPL42040-01 inhibited the TNFα-induced degradation of… More >
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