DB1055 is a HOXA9 inhibitor that competes with HOXA9 binding to DNA (blocking its DNA interaction activity). DB1055 induces in vitro cell growth reduction, cell apoptosis, and differentiation in human acute myeloid leukemia (AML) cells. DB1055 leads to monocyte-to-macrophage differentiation and exhibits antileukemic activities in a human THP-1 AML in vivo model. DB1055 does not impact human CD34 + bone marrow cells. DB1055 can be used for the research of acute myeloid leukemia [1].
In Vivo, DB1055 (20 mg/kg; i.p.; on days 1, 3, and 5; for 3 weeks) reduces THP-1-induced splenomegaly and increases hCD11b-positive THP-1 cells in NSG mice[1]. DB1055 (40 mg/kg; i.p.; on days 1, 3, and 5; for ever 3 weeks) reduces AML-associated splenomegaly and decreases blast cell counts in patient-derived AML xenograft NSG mice[1]. DB1055 (30 mg/kg; i.p.; on days 1, 3, and 5) does not result in a significant decrease in white or red blood cell counts in C57BL/6 mice, indicating that DB1055 does not inhibit normal hematopoiesis[1].
In Vitro, DB1055 (10 µM; days 1-4 post-treatment) inhibits proliferation of THP-1 cells[1]. DB1055 (1.5-5 µM; 14-day) dose-dependently inhibits colony formation by THP-1 cells[1]. DB1055 (5-15 µM; 7-day) induces cell death in THP-1 cells in a concentration-dependent manner[1]. DB1055 (5-15 µM; 7-day) induces apoptotic cell death in THP-1 cells in a concentration-dependent manner[1]. DB1055 (5 µM; 3-day and 6-day) induces morphological features of differentiation in THP-1 cells[1]. DB1055 (5-15 µM; 7-day) induces myeloid differentiation in THP-1 cells, as measured by increased CD11b and CD14 expression, in a concentration-dependent manner[1]. DB1055 (0.1-10 µM; for 15 days) has low toxicity toward normal human CD34+ cell-derived erythroid, myeloid, and megakaryocyte lineages[1]. DB1055 (0.01-10 µM) inhibits HOXA9 binding to the TLR4 and EMP1 gene promoters (IC50 = 0.28 μM (TLR4), 0.18 μM (EMP1))[1].
References:
[1]. Lambert M, et al. Induction of AML cell differentiation using HOXA9/DNA binding inhibitors as a potential therapeutic option for HOXA9-dependent AML. Hemasphere. 2024;8(5):e77. Published 2024 May 6.
In Vivo, DB1055 (20 mg/kg; i.p.; on days 1, 3, and 5; for 3 weeks) reduces THP-1-induced splenomegaly and increases hCD11b-positive THP-1 cells in NSG mice[1]. DB1055 (40 mg/kg; i.p.; on days 1, 3, and 5; for ever 3 weeks) reduces AML-associated splenomegaly and decreases blast cell counts in patient-derived AML xenograft NSG mice[1]. DB1055 (30 mg/kg; i.p.; on days 1, 3, and 5) does not result in a significant decrease in white or red blood cell counts in C57BL/6 mice, indicating that DB1055 does not inhibit normal hematopoiesis[1].
In Vitro, DB1055 (10 µM; days 1-4 post-treatment) inhibits proliferation of THP-1 cells[1]. DB1055 (1.5-5 µM; 14-day) dose-dependently inhibits colony formation by THP-1 cells[1]. DB1055 (5-15 µM; 7-day) induces cell death in THP-1 cells in a concentration-dependent manner[1]. DB1055 (5-15 µM; 7-day) induces apoptotic cell death in THP-1 cells in a concentration-dependent manner[1]. DB1055 (5 µM; 3-day and 6-day) induces morphological features of differentiation in THP-1 cells[1]. DB1055 (5-15 µM; 7-day) induces myeloid differentiation in THP-1 cells, as measured by increased CD11b and CD14 expression, in a concentration-dependent manner[1]. DB1055 (0.1-10 µM; for 15 days) has low toxicity toward normal human CD34+ cell-derived erythroid, myeloid, and megakaryocyte lineages[1]. DB1055 (0.01-10 µM) inhibits HOXA9 binding to the TLR4 and EMP1 gene promoters (IC50 = 0.28 μM (TLR4), 0.18 μM (EMP1))[1].
References:
[1]. Lambert M, et al. Induction of AML cell differentiation using HOXA9/DNA binding inhibitors as a potential therapeutic option for HOXA9-dependent AML. Hemasphere. 2024;8(5):e77. Published 2024 May 6.