GSK-J1 lithium salt

GSKJ1 is a selective and potent histone demethylase inhibitor (GSK-J1) that has significant activity (IC50 60 nM for human JmjD3) in vitro and in cells using an ester derivative (GSK-J4: 1 µM < IC50 < 10 µM; e.g. 9 µM in primary human macrophages). The pyridine regio-isomer GSK-J2 displays significantly less on-target activity (IC50 > 100 µM for human JmjD3) and thus can be used as control for target effects in vitro, and as ester derivative (GSK-J5) in cells. Recent data has shown that GSK-J1 also shows some activity (IC50 950 nM for Jarid1b, IC50 1.76 uM for Jarid1c) against H3K4me3/2/1 demethylases.

Product information

CAS Number: 2309668-29-7

Molecular Weight: 395.38

Formula: C22H22LiN5O2

Synonym:

GSK J1 lithium salt

Chemical Name: lithium(1+) 3-{[2-(pyridin-2-yl)-6-(2, 3, 4, 5-tetrahydro-1H-3-benzazepin-3-yl)pyrimidin-4-yl]amino}propanoate

Smiles: [Li+].[O-]C(=O)CCNC1=CC(=NC(=N1)C1=CC=CC=N1)N1CCC2=CC=CC=C2CC1

InChiKey: WTBLFQHAMMUILY-UHFFFAOYSA-M

InChi: InChI=1S/C22H23N5O2.Li/c28-21(29)8-12-24-19-15-20(26-22(25-19)18-7-3-4-11-23-18)27-13-9-16-5-1-2-6-17(16)10-14-27;/h1-7,11,15H,8-10,12-14H2,(H,28,29)(H,24,25,26);/q;+1/p-1

Technical Data

Appearance: Solid Power

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

Solubility: Soluble in DMSO

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:

GSK-J1 inhibits TNF-α production by human primary macrophages in an H3K27-dependent manner. GSK-J1 inhibits the demethylase activity of KDM5C with 8.5-fold increased potency compared with that of KDM5B at 1 mM α-ketoglutarate, with IC50 of 11 μM and 94 μM, respectively.GSK-J1 is selective for H3K27 demethylases of the KDM6 subfamily and specifically binds to endogenous JMJD3.

References:

1. Horton JR, et al. Characterization of a Linked Jumonji Domain of the KDM5/JARID1 Family of Histone H3 Lysine 4 Demethylases. J Biol Chem. 2016 Feb 5;291(6):2631-46.
2. Heinemann B, et al. Inhibition of demethylases by GSK-J1/J4. Nature. 2014 Oct 2;514(7520):E1-2.
3. Kruidenier L, et al. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature. 2012 Aug 16;488(7411):404-8.

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