Combined Scaffold Evaluation and Systems-level Transcriptome-Based Analysis for Accelerated Lead Optimization Reveals Ribosomal Targeting Spirooxindole Cyclopropanes.

In this study, we have combined scaffold-directed synthesis with a hybrid experimental and transcriptome analysis to identify bis-spirooxindole cyclopropanes that inhibit cancer cell proliferation through disruption of ribosomal function. These findings demonstrate the value of an integrated, biologically-inspired synthesis and assay strategy for the accelerated identification of first-in-class cancer therapeutic candidates.
PMID: 31140738 [PubMed - as supplied by publisher]

Source: ChemMedChem - May 28, 2019 Category: Chemistry Authors: Rodriguez K, Howe E, Bacher E, Burnette M, Meloche J, Meisel J, Schnepp P, Tan X, Chang M, Zartman J, Zhang S, Ashfeld BL Tags: ChemMedChem Source Type: research