| Description | SEL24-B489 is a highly effective and orally bioavailable compound that acts as a robust, type I inhibitor of both PIM and FLT3-ITD. It exhibits exceptional binding affinity with K d values of 2 nM for PIM1, 2 nM for PIM2, and 3 nM for PIM3. |
| In vitro | In MOLM-13 and to a lesser extent in MV4-11 cells, a dose-dependent disruption of cell cycle with especially pronounced depletion of the S phase after treatment with SEL24-B489, accompanied by PARP cleavage and apoptosis was observed[1]. SEL24-B489 causes a profound inhibition of S6 (S 235/236 ), but has little effect on PI3K/mTOR signaling[1]. SEL24-B489 inhibits STAT5 (Ser 726 ) and reduced expression of MCL1, whereas none of the selective inhibitors altered c-MYC abundance or induced PARP cleavage[1]. Cell Viability Assay[1]Cell Line: AZD1208, AC220 and AraC in AML cell lines. Concentration: 0-10 μM. Incubation Time: 72 h. Result: Decreased viability. |
| In vivo | SEL24-B489 (25-100 mg/kg, orally) exhibited activity in AML in vivo models[1]. SEL24-B489 induces apoptosis of DLBCL cell lines in low/sub-micromolar concentrations and exhibits activity in a xenograft model[2]. Animal Model: SCID/beige mice bearing MV-4-11 tumors (FLT3-ITD+)[1]. Dosage: 50, 75 and 100 mg/kg. Administration: Orally, twice daily. Result: Marked dose – dependent tumor reduction (67%, 74% and 82% tumor growth inhibition (TGI) for 50, 75 and 100 mg/kg daily doses, respectively). |
| Target activity | Pim1:2 nM (Kd), Pim3:3 nM (Kd), Pim2:2 nM (Kd) |
| Synonyms | SEL24-B489 |
| molecular weight | 446.143 |
| Molecular formula | C15H18Br2N4O2 |
| CAS | 1616359-00-2 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| References | 1. Wojciech Czardybon, A novel, dual pan-PIM/FLT3 inhibitor SEL24 exhibits broad therapeutic potential in acute myeloid leukemia. Oncotarget. 2018 Mar 30;9(24):16917-16931. 2. Ewa Jablonska, et al. A Novel Pan-PIM Kinase Inhibitor, SEL24-B489, Induces Apoptosis and Inhibits Proliferation of Diffuse Large B-Cell Lymphoma Cells through Inhibition of Protein Translation and Attenuation of Myc and NFkB Activity. Blood (2015) 126 (23): 706. |