Fig. 4: Discovering a novel scaffold hit of SPOP.
From: Sequence-based drug design as a concept in computational drug design
a Scheme of virtual screening protocol for small-molecule inhibitors of SPOP. b Chemical structure of 221C7 and its negative control 222A5. c 221C7 competitively inhibits puc_SBC1 peptide binding to SPOPMATH, as measured by the FP assay. Negative control 222A5 does not inhibit puc_SBC1 peptide binding to SPOPMATH. Error bars represent mean ± SEM of two independent experiments. d 221C7 disrupts protein binding between SPOPMATH and PTEN, as measured by in vitro pull-down assay. This experiment is repeated three times independently with similar results. e NMR measurement of direct binding between 221C7 and SPOPMATH. CPMG NMR spectra for 221C7 (red), 221C7 in the presence of 5 \({{{{{\rm{\mu }}}}}}\)M SPOPMATH (green). The STD spectrum for 221C7 is recorded in the presence of 5 \({{{{{\rm{\mu }}}}}}\)M SPOPMATH. f A similarity search of 221C7 was conducted, and 26 compounds were purchased, 19 of which were active in the FP assay. Source data are provided as a Source Data file.
