Daminozide --- KDM2/7 Histone Demethylases Inhibitor

Daminozide is a potent and selective small molecule inhibitor of the KDM2/7 family of human JmjC histone demethylases. It inhibits KDM2A at IC50 ~1.5 μM, PHF8 at IC50 ~0.55 μM, and KIAA1718 at IC50 ~2.1 μM. It has at least 60-fold selectivity as an inhibitor of the KDM2/7 subfamily over the other demethylase subfamily members such as KDM3A, KDM4E, KDM5C and KDM6B, and exhibits no inhibition even at 1 mM for PHD2, FIH, and BBOX1 (all of which are important 2OG oxygenases). The X-ray co-crystal structures revealed the daminozide’s inhibition mode: it binds in the 2OG binding pocket and chelates to the active site metal via its acylhydrazide carbonyl and dimethylamino groups. The selectivity of daminozide for the KDM2/7 subfamily could, at least in part, arise from a “snug fit” obtained via binding in the position trans to His247 wherein its two methyl groups are accommodated in a tight hydrophobic pocket (formed by Val255, Ile313, and Tyr257), which is conserved in the KDM2/7subfamily. Given the link between JmjC enzymes and diseases (such as cancer, metabolic disease, neurological disease, and inflammation), further studies on the biological effects of daminozide is of great interest.

Product information

CAS Number: 1596-84-5

Molecular Weight: 160.17

Formula: C6H12N2O3

Chemical Name: N-(dimethylamino)succinamic acid

Smiles: CN(C)NC(=O)CCC(O)=O

InChiKey: NOQGZXFMHARMLW-UHFFFAOYSA-N

InChi: InChI=1S/C6H12N2O3/c1-8(2)7-5(9)3-4-6(10)11/h3-4H2,1-2H3,(H,7,9)(H,10,11)

Technical Data

Appearance: Solid Power.

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

Solubility: DMSO up to 100 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:

Daminozide was used at 10-20 µM final concentration in vitro and in cellular assays.

References:

1. Rose NR, et al. Plant Growth Regulator Daminozide Is a Selective Inhibitor of Human KDM2/7 Histone Demethylases (2012) J Med Chem. 55(14):6639-43.

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

Documents