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. Author manuscript; available in PMC: 2021 Oct 16.
Published in final edited form as: ACS Chem Biol. 2020 Sep 28;15(10):2722–2730. doi: 10.1021/acschembio.0c00520

Figure 4.

Figure 4.

Molecular modeling of 26 identifies that the nitrogens in the pyrimidine ring are critical for GSPT1 degradation. (A) CC-885 (gray) bound to CRBN (green) and GSPT1 (cyan) in a ternary complex (PDB: 5HXB). (B) Docking of 26 (yellow) into PDB: 5HXB. (C) Structures of 26 and its analog 52, with the N-1 replaced with carbon. (D) Antiproliferative IC50 curves ± SD after 48 h treatments (three biological replicates; Graphpad Prism 8 software). (E) Immunoblot after 4 h treatments in MM1.S cells. Vinculin representative of 4 blots. Quantification shown as percentage of DMSO control normalized to vinculin.