Synthesis and Biological Evaluation of β-Lactam Derivatives Targeting Speckle-Type POZ Protein (SPOP)

Speckle-type POZ protein (SPOP) acts as a cullin3-RING ubiquitin ligase adaptor, which facilitates the recognition and ubiquitination of substrate proteins. Previous research suggests that targeting SPOP holds promise in the treatment of clear cell renal cell carcinoma (ccRCC). On the basis of the reported SPOP inhibitor 230D7, a series of β-lactam derivatives were synthesized in this study. The biological activity assessment of these compounds revealed E1 as the most potent inhibitor, which can disrupt the SPOP–substrate interactions in vitro and suppress the colony formation of ccRCC cells. Taken together, this study provided compound E1 as a potent inhibitor against ccRCC and offered insight into the development of the β-lactam SPOP inhibitor.