GSK J4 HCl

Catalog No.S7070

GSK J4 HCl is a cell permeable 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.

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GSK J4 HCl Chemical Structure

GSK J4 HCl Chemical Structure
Molecular Weight: 453.96

Validation & Quality Control

Quality Control & MSDS

Product Information

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Product Description

Biological Activity

Description GSK J4 HCl is a cell permeable 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.
Targets JMJD3 [1]
(Cell-free assay)
IC50 60 nM
In vitro GSK J4 HCl is an ethyl ester derivative of the JMJD3 selective histone demethylase inhibitor GSK-J1 with an IC50 value greater than 50 μM in vitro. GSK J4 HCl is used to probe the consequences of demethylation of H3K27me3. In human primary macrophages, GSK-J4 inhibits the lipopolysaccharide-induced production of cytokines, including pro-inflammatory tumour necrosis factor (TNF). In addition, GSK-J4 prevents the lipopolysaccharide-induced loss of H3K27me3 associated with the TNF transcription start sites and blocked the recruitment of RNA polymerase II. [1]
Cell Data
Cell LinesAssay TypeConcentrationIncubation TimeFormulationActivity DescriptionPMID
CUTLL1MlrES5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?MUeyJO69VQ>?NYjxWmhPTE2VTx?=NV3GU2pr[W[oZXP0d{Bk\WyuIHfyc5d1cA>?MoP1NlUyOzJ3NEm=
CUTLL1M4jzdWFxd3C2b4Ppd{Bie3OjeR?=NGrSblIzKM7:TR?=MV\EUXNQMWrpcoR2[2W|IHHwc5B1d3Orcx?=NVT0dm5bOjVzM{K1OFk>
CUTLL1MUjGeY5kfGmxbjDhd5NigQ>?MUOyJO69VQ>?MWHEUXNQMo\3bY5lfWOnczDj[YxtKGO7Y3zlJIFzemW|dB?=MVeyOVE{OjV2OR?=
CUTLL1MWfLbY5ie2ViYYPzZZk>NX3TT5l{PiEQvF2=MmrUSG1UVw>?M{T0cYxm[WS|IITvJIlv[3KnYYPl[EBJO0t{N33lNy=>MUWyOVE{OjV2OR?=
SF7761MV3LbY5ie2ViYYPzZZk>MljmOkDPxE1?MniwSG1UVw>?M1nueolv[3KnYYPld{BMOjdibXX0bJlt[XSrb36=NVrQN|R6OjV2MEG2PVM>
SF8628NV3HNIl1U2mwYYPlJIF{e2G7NIDKXWo3KM7:TR?=MWTEUXNQNVTEN|RocW6lcnXhd4V{KEt{ODDt[ZRpgWyjdHnvci=>MkK5NlU1ODF4OUO=
H3.3M4fwcGtqdmG|ZTDhd5NigQ>?MXS2JO69VQ>?NF7RbZNFVVORMWDpcoNz\WG|ZYOgT|I6KG2ndHj5cIF1cW:wNYHvN4piOjV2MEG2PVM>
SF9012MVvLbY5ie2ViYYPzZZk>Mn7wOkDPxE1?MUfEUXNQMn3MbY5kemWjc3XzJGs{OCCvZYTofYxifGmxbh?=NITRXYUzPTRyMU[5Ny=>
SF9402NUHDO|FuU2mwYYPlJIF{e2G7M3PHflYh|ryPNUTlZ4tCTE2VTx?=MVLpcoNz\WG|ZYOgT|MyKG2ndHj5cIF1cW:wNWP6S5ZHOjV2MEG2PVM>
SF9427MYPLbY5ie2ViYYPzZZk>NH7D[2M3KM7:TR?=MXLEUXNQNI\5UHVqdmO{ZXHz[ZMhUzN{IH3leIh6dGG2aX;uNIn1ZlYzPTRyMU[5Ny=>
human astrocytesM2jjZ2tqdmG|ZTDhd5NigQ>?MVO2JO69VQ>?NFv4ZmVFVVORNHPWV|dqdmO{ZXHz[ZMhUzN|IH3leIh6dGG2aX;uMUSyOVQxOTZ7Mx?=
SF7761M3myNmdzd3e2aDDpcohq[mm2b4L5JIF{e2G7NGfSPJQ3KM7:TR?=MYHEUXNQMXzpcohq[mm2czDLNldOKGeuaX;tZUBk\WyuIHfyc5d1cA>?NI\uc2YzPTRyMU[5Ny=>
SF8628MVjHdo94fGhiaX7obYJqfG:{eTDhd5NigQ>?MVm2JO69VQ>?M{fJfGROW09?NELqeIRqdmirYnn0d{BMOjiPIHfsbY9u[SClZXzsJIdzd3e2aB?=M{[wXlI2PDBzNkmz
H3.3MlnDS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?Mk\HOkDPxE1?MVHEUXNQM3n3bIlvcGmkaYTzJGszQU1iZ3zpc41iKGOnbHyg[5Jwf3SqNFPBN5YzPTRyMU[5Ny=>
SF9012MkTwS5Jwf3SqIHnubIljcXSxcomgZZN{[Xl?MkfJOkDPxE1?MlzmSG1UVw>?MUXpcohq[mm2czDLN|BOKGeuaX;tZUBk\WyuIHfyc5d1cA>?M{HwXVI2PDBzNkmz
SF9402M2Lq[Wdzd3e2aDDpcohq[mm2b4L5JIF{e2G7NH3IWno3KM7:TR?=M3\iRWROW09?M2POZYlvcGmkaYTzJGs{OU1iZ3zpc41iKGOnbHyg[5Jwf3SqNXrj[oZbOjV2MEG2PVM>
SF9427M3zrNWdzd3e2aDDpcohq[mm2b4L5JIF{e2G7MlHwOkDPxE1?M3uxemROW09?MWjpcohq[mm2czDLN|JOKGeuaX;tZUBk\WyuIHfyc5d1cA>?NHzCVnMzPTRyMU[5Ny=>
human astrocytesM{myR2dzd3e2aDDpcohq[mm2b4L5JIF{e2G7NF\rU5o3KM7:TR?=NVn1Wmd3TE2VTx?=NXPiTmNKcW6qaXLpeJMhUzN|TTDncIlwdWFiY3XscEBoem:5dHi=NY\h[4FsOjV2MEG2PVM>
TG neuronsNGjUcJlHfW6ldHnvckBie3OjeR?=Mmq5OVAh|ryPMly1SG1UVw>?M4HNVIlvcGmkaYTzJGhUXi1zIILlZYN1cX[jdHnvckBnem:vIIPlcpNwenlibnX1do9vew>?NXPqcIZ5OjV3NUK3NlA>
Th17M{K4T2Z2dmO2aX;uJIF{e2G7NVXZPG1wQDBibl2=NFPYeGpFVVORM2THd4lvcGmkaYTzJINmdGxiZHnm[oVz\W62aXH0bY9vMorENlU5PDB7OUO=
β-cellsMlqxSpVv[3Srb36gZZN{[Xl?NXrrNGl{OjBizszNMV;EUXNQNFv0NnNjdHWwdIOgTWZP|rNuIFnsMVHPuixiYX7kJHRPTs7zLXnu[JVk\WRiY3jlcY9scW6nIHflcoUh\XiycnXzd4lwdg>?NXHPXFhpOjZ3MEWxPVM>
β-cellsMWnGeY5kfGmxbjDhd5NigQ>?MmXINlAh|ryPMom4SG1UVw>?NVTyd5NFcW6mdXPld{DPui2lZXzsJIR6e2[3bnP0bY9vMoPtNlY2ODVzOUO=
ESCsNVnVc3BDTnWwY4Tpc44h[XO|YYm=NWC5SHhnOS564pEFxtVONYDEXHZqTE2VTx?=MoHzbY5lfWOnczDEUmEh\GGvYXflJIFtd26pIIfpeIgh[WO2aY\heIlwdiCxZjD0bIUhTE6DIHThcYFo\SC{ZYPwc45{\Q>?MlvGNlY4PTlzN{W=
Raw 264.7NIPVd4pHfW6ldHnvckBie3OjeR?=Mkn0NE45OTl{4pEFxtVONX\nUIJJTE2VTx?=MUjpcohq[mm2czDUUmYu|rFicILv[JVkfGmxbh?=MknRNlY4PzZ|NkC=

... Click to View More Cell Line Experimental Data

In vivo
Features

Protocol(Only for Reference)

Kinase Assay: [1]

Histone Demethylase AlphaScreen Inhibition of histone demethylases is assessed using the histone demethylase AlphaScreen assay (Amplified Luminescence Proximity Homogenous Assay). This assay uses a biotinylated peptide substrate and relies on detection of the product methyl mark using a specific antibody coupled to protein-A acceptor beads and a Steptavidin donor bead to capture the peptide. In brief, recombinant demethylase enzymes are incubated in the presence of Fe2+ in the form of Ferrous Ammonium Sulphate (FAS), -ketoglutarate (KG) and biotinylated peptide substrate. L-Ascorbic Acid is included to provide a reducing environment and prevent oxidation of Fe2+. After incubation with peptide substrate the presence of the product is detected using AlphaScreen technology. The demethylase AlphaScreen assays are performed in 384-well plate format using white proxiplates. All steps are carried out in assay buffer (50 mM HEPES pH 7.5, 0.1% (w/v) BSA and 0.01 % (v/v) Tween-20). FAS is dissolved fresh each day in 20 mM HCl to a concentration of 400 mM and diluted to 1.0 mM in deionized water. All other components are dissolved fresh each day in deionized water. For IC50 determinations 5 μL of assay buffer containing demethylase enzyme is transferred to wells of a 384-well proxiplate. Titrations of compound (0.1 μL) are transferred to each well and the enzymes allowed to pre-incubate for 15 minutes with compound (final concentration of DMSO is 1%). The enzyme reaction is initiated by addition of 5 μL of a substrate mix consisting of α-KG, FAS, L-Ascorbic Acid and biotinylated peptide substrate and the reaction incubated for the indicated time at room temperature. The enzyme reaction is stopped after the indicated time by addinton of 5 μL of EDTA (7.5 mM final concentration in assay buffer). Streptavidin Donor beads (0.08 mg/ml) and Protein-A conjugated acceptor beads (0.08 mg/ml) are pre-incubated for 1 hour with an antibody to the product methyl mark and the presence of biotin-H3-product is detected by addition of 5 μL of the preincubated AlphaScreen beads (final concentrations of 0.02 mg/ml with respect to acceptor and donor beads). Detection is allowed to proceed for 1 hour at room temperature and the assay plates read in a BMG Labtech Pherastar FS plate reader. Data are normalized to the no enzyme control and the IC50 determined from the nonlinear regression curve fit using GraphPad Prism 5.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Kruidenier L, et al. Nature, 2012, 488(7411), 404-408.

Chemical Information

Download GSK J4 HCl SDF
Molecular Weight (MW) 453.96
Formula

C24H27N5O2.HCl

CAS No. 1373423-53-0(free base)
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 90 mg/mL warming (198.25 mM)
Ethanol 90 mg/mL warming (198.25 mM)
Water <1 mg/mL (<1 mM)
In vivo 2% DMSO+dd H2O 10 mg/mL
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name β-Alanine, N-[2-(2-pyridinyl)-6-(1,2,4,5-tetrahydro-3H-3-benzazepin-3-yl)-4-pyrimidinyl]-, ethyl ester, hydrochloride (1:1)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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