GSK-J4 free base

• CAS: 1373423-53-0
• Catalog Number: ACM1373423530
• Category: Others
• Molecular Weight: 417.51
• Molecular Formula: C24H27N5O2
• Description: GSK-J4 is a cell permeable, potent and selective histone demethylase. GSK-J4 is a prodrug of GSK J1, which is the first selective inhibitor of the H3K27 histone demethylase JMJD3 and UTX with IC50 of 60 nM in a cell-free assay and inactive against a panel of demethylases of the JMJ family. GSK-J4 is used to probe the consequences of demethylation of H3K27me3. GSK-J4 inhibits the lipopolysaccharide-induced production of cytokines, including pro-inflammatory tumour necrosis factor (TNF).
• Synonyms: GSK-J4 free base; GSK-J-4; GSK-J 4; GSK-J4
• IUPAC Name: ethyl 3-((2-(pyridin-2-yl)-6-(1,2,4,5-tetrahydro-3H-benzo[d]azepin-3-yl)pyrimidin-4-yl)amino)propanoate
• Canonical SMILES: O=C(OCC)CCNC1=NC(C2=NC=CC=C2)=NC(N3CCC4=CC=CC=C4CC3)=C1
• InChI: InChI=1S/C24H27N5O2/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)
• InChI Key: WBKCKEHGXNWYMO-UHFFFAOYSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >3 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Alternative CAS: 1797983-09-5 (HCl); 1373423-53-0 (free base)
• Biological Target: GSK-J4 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 inhibits LPS-induced TNF-α production in human primary macrophages with an IC50 of 9 μM.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 69.04; H, 6.52; N, 16.77; O, 7.66
• Exact Mass: 417.2165
• HS Tariff Code: 2934.99.03.00
• In Vitro Activity: Hence, this study analyzed the LDH level in the culture medium of AC16 cell (Figure 1F) and neonatal rat cardiomyocyte (NRCM) (Figure 1G) and found that PA (palmitic acid) could stimulate LDH release, while GSK-J4 significantly reduced its releasement.; Reference: Front Cardiovasc Med. 2022 Jun 2;9:907747. https://pubmed.ncbi.nlm.nih.gov/35722096/
• In Vivo Activity: There was a significant increase in the amount of α-SMA, fibronectin, and fibronectin as well as collagen IV protein accumulations (Figure 4), whereas in STZ (streptozotocin)-induced diabetic mice that were treated with GSK-J4, the staining areas of fibronectin and collagen IV fibrosis-related proteins were reduced relative to those that were not treated with GSK-J4 (Figure 3). In addition, the accumulation of α-SMA, fibronectin, and collagen IV proteins in the kidneys of the diabetic mice that were given GSK-J4 was also significantly lower than in those that were not given GSK-J4 (Figure 4).; Reference: Int J Mol Sci. 2022 Aug 20;23(16):9407. https://pubmed.ncbi.nlm.nih.gov/36012674/
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).