Seclidemstat (formerly also known as SP-2577; SP2577) is a novel, potent small molecule inhibitor of epigenetic enzyme LSD1 (lysine-specific demethylase 1) with anticancer activity. It inhibits LSD1 with a mean IC50 of 127 nM. Seclidemstat has the potential for the treatment of cancer. It is currently undergoing Phase 1 clinical trial in Ewing's sarcoma. Seclidemstat represents a paradigm shift in the treatment of cancer and Ewing sarcoma is a devastating pediatric, adolescent and young adult bone cancer where no targeted therapies are currently available.

Physicochemical Properties

Molecular Formula	C20H23CLN4O4S
Molecular Weight	450.93
Exact Mass	450.112
CAS #	1423715-37-0
Related CAS #	Seclidemstat mesylate;2044953-70-8
PubChem CID	135565033
Appearance	Off-white to yellow solid powder
Density	1.4±0.1 g/cm3
Index of Refraction	1.645
LogP	4.07
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	5
Heavy Atom Count	30
Complexity	734
Defined Atom Stereocenter Count	0
SMILES	C/C(=N\NC(=O)C1=CC(=CC=C1)S(=O)(=O)N2CCN(CC2)C)/C3=C(C=CC(=C3)Cl)O
InChi Key	MVSQDUZRRVBYLA-HYARGMPZSA-N
InChi Code	InChI=1S/C20H23ClN4O4S/c1-14(18-13-16(21)6-7-19(18)26)22-23-20(27)15-4-3-5-17(12-15)30(28,29)25-10-8-24(2)9-11-25/h3-7,12-13,26H,8-11H2,1-2H3,(H,23,27)/b22-14+
Chemical Name	N''-[(1E)-1-(5-chloro-2-hydroxyphenyl)ethylidene]- 3-(4-methylpiperazine-1-sulfonyl)benzohydrazid
Synonyms	SP-2577;SP 2577;SP2577
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	IC50: 127 nM (LSD1)[1]
ln Vitro	In cells with an IC50 ranging from 0.013 to 2.819 μM (COV434, BIN67, SCCOHT-1, TOV21G, SKOV3, A427, H522, A549, H1299, G401, G402, HCC15 cells), seclidemstat (72 hours) inhibits the growth of tumors caused by SWI/SNF mutations. seclidemstat (72 hours) increases IFNβ immunity and endogenous retrovirus (ERV) expression in SCCOHT cell lines (SCCOHT-1), BIN67, and COV434 cells [2]. seclidemstat (72 hours) increases PD-L1 expression in SCCOHT COV 434 pIND 20 BRG1-2.7 cell line [2].
ln Vivo	Seclidemstat reduces tumor volume at 40, 80 mg/kg by i.p. and also shows such effect at 80 mg/kg via p.o. dosing.
References	[1]. Reversible Lysine Specific Demethylase 1 (LSD1) Inhibitors: A Promising Wrench to Impair LSD1 [published correction appears in J Med Chem. 2021 May 13;64(9):6410-6411]. J Med Chem. 2021;64(5):2466-2488. [2]. The novel reversible LSD1 inhibitor SP-2577 promotes anti-tumor immunity in SWItch/Sucrose-NonFermentable (SWI/SNF) complex mutated ovarian cancer. PLoS One. 2020;15(7):e0235705. Published 2020 Jul 10.
Additional Infomation	Seclidemstat is an orally available, reversible, noncompetitive inhibitor of lysine-specific demethylase 1 (LSD1, or KDM1A), with potential antineoplastic activity. Upon oral administration, seclidemstat reversibly inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the di- and mono-methylated forms of lysine at position 4 of histone 3 (H3K4) to mono- and unmethylated H3K4, respectively. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor suppressor genes. This may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. In addition, LSD1 demethylates mono- or di-methylated H3K9 which increases gene expression of tumor promoting genes; inhibition of LSD1 promotes H3K9 methylation and decreases transcription of these genes.

Solubility Data

Solubility (In Vitro)

DMSO:10 mM Water:N/A Ethanol:N/A

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.61 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2 mg/mL (4.44 mM) in 1.6% DMA 5% Ethanol 45% PEG400 48.4% PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). Solubility in Formulation 3: 10 mg/mL (22.18 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2176 mL	11.0882 mL	22.1764 mL
	5 mM	0.4435 mL	2.2176 mL	4.4353 mL
	10 mM	0.2218 mL	1.1088 mL	2.2176 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.