DP-15 is a BRD4 and GSPT1 PROTAC degrader with DC50 values of 0.48 nM and 5.25 nM, respectively. DP-15 induces ubiquitination and degradation of BRD4 and GSPT1. DP-15 induces Apoptosis. DP-15 exerts anticancer activity against acute myeloid leukemia and non-Hodgkin's lymphoma cells. DP-15 can be used in studies related to acute myeloid leukemia and non-Hodgkin's lymphoma [1]. (Pink: BRD4 and GSPT1 ligand; Blue: Cereblon ligand; Black: linker ).
In Vivo, DP-15 (2.5 mg/kg; i.p.; twice daily; 18 days) significantly reduces AML tumor burden, decreases leukemic cell infiltration in peripheral blood, spleen, and bone marrow, and prolongs survival in NSG mice without causing significant body weight loss[1].
In Vitro, DP-15 (0.1 μM; 72 h) potently inhibits the proliferation of MOLM13 acute myeloid leukemia (AML) cells, with an IC50 of 8.55 nM after 72 h of treatment, and reduces cell viability to 7.02% at a concentration of 0.1 μM[1]. DP-15 (72 h) potently inhibits the proliferation of OCI-AML3, NB4, THP-1 and HL-60 acute myeloid leukemia (AML) cell lines, with IC50 values ranging from 2.69 nM to 17.96 nM after 72 h of treatment[1]. DP-15 (72 h) potently inhibits the proliferation of SU-DHL-1, Raji, Karpas299 and Daudi non-Hodgkin's lymphoma (NHL) cell lines, with IC50 values ranging from 6.29 nM to 25.48 nM after 72 h of treatment[1]. DP-15 (0.01-1000 nM; 6-24 h) efficiently and selectively degrades BRD4 and GSPT1 in MOLM13 acute myeloid leukemia (AML) cells in a time- and concentration-dependent manner; after 24 h of treatment, its DC50 value against BRD4 is 0.48 nM, while that against GSPT1 is 5.25 nM, and it also downregulates c-Myc[1]. DP-15 (0.1 μM; 6-24 h) induces time-dependent early apoptosis in MOLM13 acute myeloid leukemia (AML) cells, with approximately 70% of cells being Annexin V-positive after 24 h of treatment with 0.1 μM[1]. DP-15 (0.1 μM; 6-12 h) induces G1-phase cell cycle arrest in MOLM13 acute myeloid leukemia (AML) cells after 6 h and 12 h of treatment[1].
References:
[1]. Xu Y, et al. Discovery of highly potent dual GSPT1/BRD4 degraders with anti-AML activity. European journal of medicinal chemistry. 2025 Apr 15;288:117381.
In Vivo, DP-15 (2.5 mg/kg; i.p.; twice daily; 18 days) significantly reduces AML tumor burden, decreases leukemic cell infiltration in peripheral blood, spleen, and bone marrow, and prolongs survival in NSG mice without causing significant body weight loss[1].
In Vitro, DP-15 (0.1 μM; 72 h) potently inhibits the proliferation of MOLM13 acute myeloid leukemia (AML) cells, with an IC50 of 8.55 nM after 72 h of treatment, and reduces cell viability to 7.02% at a concentration of 0.1 μM[1]. DP-15 (72 h) potently inhibits the proliferation of OCI-AML3, NB4, THP-1 and HL-60 acute myeloid leukemia (AML) cell lines, with IC50 values ranging from 2.69 nM to 17.96 nM after 72 h of treatment[1]. DP-15 (72 h) potently inhibits the proliferation of SU-DHL-1, Raji, Karpas299 and Daudi non-Hodgkin's lymphoma (NHL) cell lines, with IC50 values ranging from 6.29 nM to 25.48 nM after 72 h of treatment[1]. DP-15 (0.01-1000 nM; 6-24 h) efficiently and selectively degrades BRD4 and GSPT1 in MOLM13 acute myeloid leukemia (AML) cells in a time- and concentration-dependent manner; after 24 h of treatment, its DC50 value against BRD4 is 0.48 nM, while that against GSPT1 is 5.25 nM, and it also downregulates c-Myc[1]. DP-15 (0.1 μM; 6-24 h) induces time-dependent early apoptosis in MOLM13 acute myeloid leukemia (AML) cells, with approximately 70% of cells being Annexin V-positive after 24 h of treatment with 0.1 μM[1]. DP-15 (0.1 μM; 6-12 h) induces G1-phase cell cycle arrest in MOLM13 acute myeloid leukemia (AML) cells after 6 h and 12 h of treatment[1].
References:
[1]. Xu Y, et al. Discovery of highly potent dual GSPT1/BRD4 degraders with anti-AML activity. European journal of medicinal chemistry. 2025 Apr 15;288:117381.