Bomedemstat ditosylate

Bomedemstat (IMG-7289) ditosylate is an oral and irreversible inhibitor of the epigenetically active lysine-specific demethylase 1 (LSD1) in mouse models of myeloproliferative neoplasms (MPNs). Bomedemstat can be used for the research of acute myelogenous leukemia (AML) and myelofibrosis (MF). Antineoplastic activity[1].

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Histone Demethylase

Bomedemstat (IMG-7289) ditosylate selectively inhibits proliferation and induced apoptosis of JAK2V617F cells by concomitantly increasing expression and methylation of p53, and, independently, the pro-apoptotic factor PUMA and by decreasing the levels of its antiapoptotic antagonist BCL-XL[1].  Bomedemstat (25  nM, 50 nM) ditosylate and Ruxolitinib (175 nM) synergize in inhibiting JAK2V617F-driven proliferation[1]. Bomedemstat (50 and 100 nM) ditosylate exerts a pro-apoptotic effect on 3 key regulators of programmed cell death, TP53, BCL-XL, and PUMA[1]. Cell Viability Assay[1] Cell Line: The human cell lines SET-2 (ATCC 608) and HEK293 Concentration: 25  nM, 50 nM Incubation Time: 96 hours Result: 25 nM alone significantly reduced colony formation. Western Blot Analysis[1] Cell Line: SET-2 cells Concentration: 50 and 100 nM Incubation Time: Result: Decreased levels of the antiapoptotic protein BCL-XL and increased levels of the pro-apoptotic protein PUMA.

Once-daily treatment with Bomedemstat (IMG-7289; 45 mg/kg) ditosylate normalizes or improves blood cell counts, reduces spleen volumes, restores normal splenic architecture, and reduces bone marrow fibrosis[1]. Animal Model: Mx1cre-Jak2V617F 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.

[1]. Jonas S Jutzi,et al. LSD1 Inhibition Prolongs Survival in Mouse Models of MPN by Selectively Targeting the Disease Clone. Hemasphere.2018 Jun 8;2(3):e54.