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. Author manuscript; available in PMC: 2021 Jul 9.
Published in final edited form as: J Med Chem. 2020 Jun 15;63(13):7186–7210. doi: 10.1021/acs.jmedchem.0c00456

Figure 5.

Figure 5.

BET inhibitor 27 is a potent antiproliferative agent in breast cancer cell lines resistant to tamoxifen, AIs, CDK4/6 inhibitors, and fulvestrant. (A–E) Concentration-dependent response to compound 27 (red) compared to 1 (blue) and 4OHT (TAM, brown), with potency for 27 annotated. (A) 27 dose-dependently inhibited the proliferation of parental MCF-7:WS8 cells that are sensitive to growth inhibition by tamoxifen. Compound 27 dose-dependently inhibited the proliferation of tamoxifen resistant MCF-7:5C (B) and MCF-7:TAM1 (C) cells with superior potency to 1. Compounds 27 and 1 dose-dependently inhibited the proliferation of tamoxifen sensitive parental T47D cells (D) and ESR1 D538G mutant T47D/TDG cells (E), with no significant right-shift in potency in the ESR1 mutant cell line. (F) Compound 27 dose-dependently inhibited the proliferation of MCF-7:CPR cells that are resistant to tamoxifen (brown. 1 μM) and palbociclib (green. 1 μM). (G) Comparison of 27 with 1 and 5 in fulvestrant-resistant MCF-7:CFR cell proliferation assay using drug washout after 3 h, by replacing media after incubation with drug for 3 h and measuring cell viability after 5 days. Solid bars show no washout. Hashed bars show washout treatment.