5.09703

LSD1 Inhibitor VII, SP-2509

• Synonym(s): LSD1 Inhibitor VII, SP-2509, BHC110 Inhibitor VII, Histone Lysine Demethylase Inhibitor XIV, KIAA1718 Inhibitor VII, LSD Inhibitor VII, SP-2509
• Empirical Formula (Hill Notation): C₁₉H₂₀ClN₃O₅S
• CAS Number: 1423715-09-6
• Molecular Weight: 437.90
• UNSPSC Code: 12352200
• NACRES: NA.77

Properties

• assay: ≥98% (HPLC)
• Quality Level: 100
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: off-white
• solubility: DMSO: 100 mg/mL
• storage temp.: 2-8°C
• InChI: 1S/C19H20ClN3O5S/c1-13(17-12-15(20)5-6-18(17)24)21-22-19(25)14-3-2-4-16(11-14)29(26,27)23-7-9-28-10-8-23/h2-6,11-12,24H,7-10H2,1H3,(H,22,25)/b21-13+
• InChI key: NKUDGJUBIVEDTF-FYJGNVAPSA-N

Description

General description

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).

Biochem/physiol Actions

Cell permeable: yes

Primary Target
LSD1

Reversible: yes

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

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

Other Notes

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

Legal Information

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

Safety Information

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable