GSK-J4 hydrochloride

GSK-J4 hydrochloride is a potent dual inhibitor of H3K27me3/me2-demethylases JMJD3/KDM6B and UTX/KDM6A with IC50s of 8.6 and 6.6 μM, respectively. GSK-J4 hydrochloride inhibits LPS-induced TNF-α production in human primary macrophages with an IC50 of 9 μM. GSK-J4 hydrochloride is a cell permeable prodrug of GSK-J1.

Product information

CAS Number: 1797983-09-5

Molecular Weight: 453.96

Formula: C24H28ClN5O2

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

Smiles: Cl.CCOC(=O)CCNC1C=C(N=C(N=1)C1=CC=CC=N1)N1CCC2=CC=CC=C2CC1

InChiKey: TYXWLTBYINKVNT-UHFFFAOYSA-N

InChi: InChI=1S/C24H27N5O2.ClH/c1-2-31-23(30)10-14-26-21-17-22(28-24(27-21)20-9-5-6-13-25-20)29-15-11-18-7-3-4-8-19(18)12-16-29;/h3-9,13,17H,2,10-12,14-16H2,1H3,(H,26,27,28);1H

Technical Data

Appearance: Solid Power

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

Solubility: DMSO : 62.5 mg/mL (137.68 mM; Need ultrasonic).

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-J4 Hydrochloride has cellular activity in Flag-JMJD3-transfected HeLa cells, in which GSK-J4 prevents the JMJD3-induced loss of nuclear H3K27me3 immunostaining. Administration of GSK-J4 increases total nuclear H3K27me3 levels in untransfected cells. GSK-J4 significantly reduces the expression of 16 of 34 LPS-driven cytokines, including tumour-necrosis factor-α (TNF-α). GSK-J4 Hydrochloride (5 μM; 48 hours) causes a more than 3-fold increase in mouse podocyte H3K27me3 content. H3K27me3 levels in cultured podocytes, GSK-J4 reduces Jagged-1 mRNA and Jagged-1 protein levels. Correspondingly, when exposed podocytes to the inducer of dedifferentiation TGF-β1, pretreatment with GSK-J4 preventes both the increase in intracellular N1-ICD levels and the increase in α-SMA and the decrease in podocin mRNA levels. GSK-J4 Hydrochloride (10, 25 nM) acts upon DCs promoting the differentiation of Treg cells, improving Treg stability and suppressive capacities, without affecting the differentiation of Th1 and Th17 cells. GSK-J4 Hydrochloride inhibits JMJD3 expression that is induced by TGF-β1. GSK-J4 Hydrochloride inhibits H3K4 demethylation at Xist, Nodal, and HoxC13 in female embryonic stem cells.

In Vivo:

GSK-J4 Hydrochloride (10 mg/kg; i.p.; thrice-weekly for 10 weeks) attenuates the development of kidney disease in diabetic mice. GSK-J4 Hydrochloride (0.5 mg/kg, i.p.) significantly reduces the severity and delays the onset of the disease of the mouse model of experimental autoimmune encephalomyelitis.

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