IC50: 0.1-1 μM (BAP1)[1]
BAP1-IN-1 (Compound 8) is a BRCA1 associated protein 1 (BAP1) catalytic activity inhibitor with an IC50 of 0.1-1 μM[1].
BAP1-IN-1 (Compound 8) (1 μM; 30 min) specifically inhibits BAP1 not just in vitro but also within the cellular context[1].
BAP1-IN-1 (0.1 μM; 24 h) significantly alters 240 genes in BAP1-WT cells, whereas only 33 transcripts are changed in BAP1-KO cells, demonstrating that the gene expression changes mainly depend on the presence of BAP1 protein[1].
BAP1-IN-1 (0-10 μM; 72 h) selectively inhibits cells with ASXL1 GOF mutations[1].
Western Blot Analysis[1]
| Cell Line: | CAL51 cells |
| Concentration: | 1 μM |
| Incubation Time: | 30 min |
| Result: | Remarkably inhibited BAP1 catalytic activity. |
Cell Viability Assay[1]
| Cell Line: | THP1, MOML13, K562, THP1-ASXL1-WT and THP1-ASXL1-Y591fs cells |
| Concentration: | 0, 0.1, 0.3, 1, 3 and 10 μM |
| Incubation Time: | 72 h |
| Result: | K562 cells (ASXL1-Y591*) were significantly more sensitive to the treatment. Cells with ASXL1fs mutations were ten times more sensitive to the treatment. |
BAP1-IN-1 (Compound 8) (50 mg/kg/d; i.p.; 4 weeks) delays the progression of ASXL1-mutant leukemia and improves survival in mice[1].
| Animal Model: | NSGS mice, K562 (ASXL1-WT/Y591*) xenograft model and patient-derived tumor cells (ASXL1-WT/Q588*) model[1] |
| Dosage: | 50 mg/kg/d |
| Administration: | Intraperitoneal injection, drug treatments were started at day 28 after transplantation |
| Result: | Significantly delayed progression of disease in both models. |
[1]. Wang L, et al. Epigenetic targeted therapy of stabilized BAP1 in ASXL1 gain-of-function mutated leukemia. Nat Cancer. 2021 May;2(5):515-526.