Bomedemstat ditosylate

Bomedemstat, also known as IMG-7289, is a lysine-specific histone demethylase 1 (LSD1) inhibitor with antineoplastic activity. Bomedemstat may be useful in the treatment of acute myeloid leukaemia, myelodysplastic syndrome, and Myelofibrosis. IMG-7289 selectively inhibited proliferation and induced apoptosis of JAK2 V617F 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 BCLXL. 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.

Product information

CAS Number: 1990504-72-7

Molecular Weight: 864.02

Formula: C42H50FN7O8S2

Chemical Name: bis(4-methylbenzene-1-sulfonic acid); N-[(2S)-5-{[(1R, 2S)-2-(4-fluorophenyl)cyclopropyl]amino}-1-(4-methylpiperazin-1-yl)-1-oxopentan-2-yl]-4-(1H-1, 2, 3-triazol-1-yl)benzamide

Smiles: CN1CCN(CC1)C(=O)[C@H](CCCN[C@@H]1C[C@H]1C1=CC=C(F)C=C1)NC(=O)C1C=CC(=CC=1)N1C=CN=N1.CC1C=CC(=CC=1)S(O)(=O)=O.CC1C=CC(=CC=1)S(O)(=O)=O

InChiKey: WLRWBXFBIJMKHG-DVNXTAPYSA-N

InChi: InChI=1S/C28H34FN7O2.2C7H8O3S/c1-34-15-17-35(18-16-34)28(38)25(3-2-12-30-26-19-24(26)20-4-8-22(29)9-5-20)32-27(37)21-6-10-23(11-7-21)36-14-13-31-33-36;2*1-6-2-4-7(5-3-6)11(8,9)10/h4-11,13-14,24-26,30H,2-3,12,15-19H2,1H3,(H,32,37);2*2-5H,1H3,(H,8,9,10)/t24-,25-,26+;;/m0../s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: To be determined

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

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. Bomedemstat (25  nM, 50 nM) ditosylate and Ruxolitinib (175 nM) synergize in inhibiting JAK2V617F-driven proliferation. Bomedemstat (50 and 100 nM) ditosylate exerts a pro-apoptotic effect on 3 key regulators of programmed cell death, TP53, BCL-XL, and PUMA.

In Vivo:

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.

References:

1. Fang Y, Liao G, Yu B. LSD1/KDM1A inhibitors in clinical trials: advances and prospects. J Hematol Oncol. 2019 Dec 4;12(1):129. doi: 10.1186/s13045-019-0811-9. Review. PubMed PMID: 31801559; PubMed Central PMCID: PMC6894138.
2. Jutzi JS, Kleppe M, Dias J, Staehle HF, Shank K, Teruya-Feldstein J, Gambheer SMM, Dierks C, Rienhoff HY Jr, Levine RL, Pahl HL. LSD1 Inhibition Prolongs Survival in Mouse Models of MPN by Selectively Targeting the Disease Clone. Hemasphere. 2018 Jun 8;2(3):e54. doi: 10.1097/HS9.0000000000000054. eCollection 2018 Jun. PubMed PMID: 31723778; PubMed Central PMCID: PMC6745991.

Products are for research use only. Not for human use.