LSD1 Inhibitor VII, SP-2509

A cell-permeable phenethylidene-benzohydrazide compound that acts as a potent, selective, reversible, and non-competitive inhibitor of Lysine-Specific Demethylase 1 (LSD1; IC₅₀ = 13 nM; K_i = 31 nM). Exhibits excellent selectivity over monoamine oxidases A and B (IC₅₀ >300 µM), lactate dehydrogenase, glucose oxidase, hERG, CYP1A2, CYP2D6 (IC₅₀ ≥ 10 µM), CYP2C9 (IC₅₀ = 8.04 µM) and CYP2C19 (IC₅₀ = 9.76 µM). Inhibits CYP3A4 only at >200-fold higher concentration. Reduces the proliferation of several cancer cell lines, including AN3 Ca, BT-20, MCF-7, T-47D, HT29, MIA PaCa-2 and SK-N-MC (IC₅₀ = 356, 489, 637, 649, 429, 468 and 329 nM, respectively).

A cell-permeable, lysine-specific demethylase 1 (LSD1) active site-targeting phenethylidene-benzohydrazide that inhibits LSD1 activity (IC₅₀ = 13 nM) in a reversible and substrate non-competitive (K_i = 34 nM) manner, while inhibiting CYP3A4 only at much higher concentrations (IC₅₀ = 2.61 µM) and displaying little or no potency towards CYP1A2/2C9/2C19/2D6. MAO-A/B, D-lactate dehydrogenase, glucose oxidase, and hERG (IC₅₀ ≥8.0 µM). Shown to enhance histone H3 Lys9 dimethylation (H3K9me2) in androgen-dependent prostate cancer VCaP cultures (1 to 10 µM) and effectively inhibits LSD1-dependent cancer growth (IC₅₀ in nM = 329/SK-N-MC, 356/AN3 Ca, 429/HT29, 468/MIA PaCa-2, 489/BT-20, 612/HER218, 614/HCT 116, 637/MCF-7, 649/T-47D; 96 h).

Cell permeable: yes

Primary Target
LSD1

Reversible: yes

Packaged under inert gas

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Fiskus, W., et al. 2014. Leukemia28, 2155.
Sorna, V., et al. 2013. J. Med. Chem.56, 9496.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Toxicity: Standard Handling (A)