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. Author manuscript; available in PMC: 2021 Jul 28.
Published in final edited form as: J Am Chem Soc. 2021 Mar 19;143(12):4714–4724. doi: 10.1021/jacs.1c00312

Figure 6. Blood cell counts and gut versus tumor biomarker assessments of T2 and AZD5153.

Figure 6.

(a) Analysis of blood cell populations demonstrates that, unlike free AZD5153, T2 Brush prodrug does not cause systemic toxicity normally associated with BET inhibition in bone marrow. No reduction in platelet, reticulocyte, neutrophil, and lymphocyte levels were detected (n=5) at doses resulting in superior anti-tumor efficacy of T2 compared to free AZD5153; error bars represent SD. h,i, T2 causes only minimal intestinal toxicity compared to OTX-015 as evidenced by in situ protein expression of c-Myc, biomarker for BET inhibition, in the base of crypts and preserved colonic villus epithelial surface morphology. Anti-tumor efficacy of T2 prodrug is comparable to free AZD5153 as shown by modulation of PD markers c-Myc, HEXIM1, and CD180 levels in extracted tumors. Statistical analysis performed using unpaired t test for tumor volumes and c-Myc expression and using Welch’s t test for assessment of hematologic toxicity; all groups compared to the vehicle group except where indicated otherwise. Any p-values not shown are n.s.; * p<0.05, ** p<0.01, *** p<0.001, **** p<0.0001. Scale bars: 100 μm.