HCI-2509 (SP2509) --- Reversible LSD1 Inhibitor

HCI-2509 (also named as SP2509 or LSD1-C12) is a highly potent, specific, and reversible Lysine Specific Demethylase-1 (LSD1) inhibitor. It inhibits LSD1 in biochemical assay with an IC50 ~13 nM, and has no activity against monoamine oxidase proteins MAO-A and MAO-B (>300 µM). HCI-2509 is a non-competitive inhibitor to bind LSD1, changes its solution dynamics in a manner distinct from TCP. It has minimal inhibition of CYPs and hERG, shows cellular activity against several cancer cell lines including endometrial, breast, colorectal, pancreatic, and prostate cancer (IC50 ~0.3-2.5 µM). HCI-2509 displayed sing-agent efficacy in multiple xenograft models and had good PK/PD relationship by using tumor histone H3K4 and H3K9 methylation. HCI-2509 serves as a very useful chemical probe to study the target biology of LSD1.

Product information

CAS Number: 1423715-09-6

Molecular Weight: 437.90

Formula: C19H20ClN3O5S

Synonym:

SP2509

LSD1-C12

Chemical Name: (E)-N'-(1-(5-chloro-2-hydroxyphenyl)ethylidene)-3-(morpholinosulfonyl)benzohydrazide

Smiles: C/C(=N\NC(=O)C1=CC(=CC=C1)S(=O)(=O)N1CCOCC1)/C1=CC(Cl)=CC=C1O

InChiKey: NKUDGJUBIVEDTF-FYJGNVAPSA-N

InChi: 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+

Technical Data

Appearance: Solid Power.

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

Solubility: DMSO up to 50 mM

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:

HCI-2509 was used at 1 µM in vitro.

In Vivo:

HCI-2509 was administered through IP injection at 25-30 mg/kg once per day in xenografts models.

References:

1. HCI-2509 was administered through IP injection at 25-30 mg/kg once per day in xenografts models.
2. Sorna V, et al. High-Throughput Virtual Screening Identifies Novel N'-(1-Phenylethylidene)-benzohydrazides as Potent, Specific, and Reversible LSD1 Inhibitors. (2013) J Med Chem. 56(23):9496-508.
3. Wiles ET, et al. BCL11B is up-regulated by EWS/FLI and contributes to the transformed phenotype in Ewing sarcoma. (2013) PLoS One. 8(3):e59369.
4. Bret J. Stephens, et al.: Activity of the LSD1 inhibitor HCI-2509 in ER-negative breast cancer cells. (2012) AACR Chicago. Abstract 1045. Cancer Research: April 15, 2012; Volume 72, Issue 8, Supplement 1.
5. Emily R, et al. Inhibition of LSD1 disrupts global EWS/ETS transcriptional function in Ewing sarcoma. (2014) AACR San Diego. Abstract 3679.

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

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