Bomedemstat (IMG-7289) hydrochloride is an orally active and irreversible lysine-specific demethylase 1 (LSD1) inhibitor. Bomedemstat hydrochloride can increase H3K4 and H3K9 methylation, and then alter gene expression. Bomedemstat hydrochloride shows anti-cancer activities, inhibits cancer cell proliferation and induces apoptosis[1][2].
Bomedemstat selectively inhibits proliferation and induces apoptosis of Jak2V617F cells by concomitantly increasing expression and methylation of p53[1].
Bomedemstat (50 nM-1 μM; 96 h) enhances survival, induces apoptosis via BCL-XL and PUMA in a TP53-dependent manner, and leads to cell cycle arrest[1].
Apoptosis Analysis[1]
| Cell Line: | SET-2 cells |
| Concentration: | 50 nM, 100 nM, and 1 μM |
| Incubation Time: | 96 hours |
| Result: | Decreased levels of the antiapoptotic protein BCL-XL and increased levels of the pro-apoptotic protein PUMA. |
Bomedemstat treatment (oral gavage; 45 mg/kg; once daily; 56 d) normalizes or improves blood cell counts, reduces spleen volumes, restores normal splenic architecture, and reduces bone marrow fibrosis[1].
| Animal Model: | Mx-Jak2V617F mice[1] |
| Dosage: | 45 mg/kg |
| Administration: | Oral gavage; 45 mg/kg; once daily; 56 days |
| Result: | Reduced splenomegaly significantly with a few treated mice normalizing their spleen weight, the 56-day course led to partial restoration of lymph follicles and spleen architecture by histological examination. |