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. Author manuscript; available in PMC: 2024 Apr 10.
Published in final edited form as: Cancer Cell. 2023 Mar 9;41(4):726–739.e11. doi: 10.1016/j.ccell.2023.02.010

Figure 8. DEG-77, an analog of DEG-35 has better efficacy and can block leukemic stem cell activity.

Figure 8.

(A) Pharmacokinetic study showing plasma concentration of DEG-77 over a 72 h period in mice after a single intraperitoneal injection of DEG-35 at 223 mg/kg. The plasma concentrations represent the means +/− SEM from three mice per time point. (B) Scheme showing strategy for analyzing pharmacodynamics of targets of DEG-77 in the MLL-AF9 CrbnI391V mice model. (C) Western blot analysis of targets IKZF2, CK1α and GSPT1 of leukemic bone marrow cells from mice treated with DEG-77 at 223 mg/kg, at indicated time point. (D) Colony assay of leukemic cells from bone marrow and spleen of mice treated with DMSO or DEG-77 24 h post treatment. Data shown is the means +/− SEM of n=3 samples for each condition. Student’s t test, *p < 0.05. (E, F) Survival curves of BL/6 mice transplanted with (E) MLL-AF9 CrbnI391V cells treated with DMSO or DEG-77 at dose of 223mg/kg weekly or (F) secondarily transplanted. ****p < 0.0001 log-rank test. n=10 mice for each group. (G) Survival curve of NSG mice transplanted with MOLM-13 cells and treated with DMSO (n=10) or DEG-77 (n=9) treated at 223mg/kg weekly. **p < 0.01 log-rank test. (H) Western blot analysis of MOLM-13 cells sorted from bone marrow of NSG mice 24h after drug treatment. (I) Survival curve of NSG mice transplanted with AML PDX#2 treated with DMSO (n=15) or DEG-77 (n=5) at dose of 223mg/kg, weekly from 4 weeks post-transplant. **p < 0.01 log-rank test. (J) Engraftment frequency of AML PDX cells measured by flow cytometry by hCD45 using bone marrow aspirates at 4 weeks post-transplant (left panel) before and (right panel) one week after a single dose of DEG-77 treatment. Data shown is means +/− SEM of the indicated samples as shown. Student’s t test, ***p < 0.001. (K) Survival curve of non-irradiated CrbnI391V mice transplanted with MLL-AF9 CrbnI391V cells treated with DMSO or DEG-77 at dose of 223 mg/kg weekly. **p < 0.01 log-rank test. n=10 mice for each group. (L) Disease burden shown by frequency of GFP positive cells (MLL-AF9 CrbnI391V cells) in bone marrow or spleen at time of sacrifice. Data shown is means +/− SEM of the indicated samples as shown. Student’s t test, *p < 0.05. See also Figure S8.