Bomedemstat

Bomedemstat (IMG-7289), an orally active and irreversible lysine-specific demethylase 1 (LSD1) inhibitor, shows activity in mouse myeloproliferative neoplasm (MPN) models. This compound exhibits antineoplastic effects and can be used for acute myeloid leukemia (AML) and myelofibrosis (MF) research.

Bomedemstat (50 nM-1 μM, 96 hours) treatment of SET-2 cells increases survival and induces apoptosis via BCL-XL and PUMA in a TP53-dependent manner, leading to cell cycle arrest. [1]

Once-daily treatment with IMG-7289 normalized or improved blood cell counts, reduced spleen volumes, restored normal splenic architecture, and reduced bone marrow fibrosis. Most importantly, LSD1 inhibition lowered mutant allele burden and improved survival [1]. Animal Model: Mx1cre-Jak2 V617F mice [1] Dosage: 45 mg/kg Administration: Administered daily by oral gavage for either 14, 42, or 56 consecutive days Result: In this Mx-Jak2V617F model of myeloproliferative neoplasm (MPN), mice developed severe splenomegaly (up to 10-fold increase in spleen weight). Splenic architecture was completely destroyed, eliminating demarcation of the white and red pulp. Treatment significantly reduced splenomegaly with a few treated mice normalizing their spleen weight. Remarkably, the 56-day course led to partial restoration of lymph follicles and spleen architecture by histological examination.