GSK484

Synonym(s):((3S,4R)-3-Amino-4-hydroxypiperidin-1-yl)(2-(1-(cyclopropylmethyl)-1H-indol-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone hydrochloride;AOB6992;GSK 484;GSK-484 hydrochloride;GTPL8577

CAS NO.：1652591-81-5
Empirical Formula: C27H32ClN5O3
Molecular Weight: 510.04
Update Date: 2024-11-07 21:39:59

What is GSK484?

Description

GSK484 is a reversible inhibitor of PAD4 (IC₅₀ = 50 nM) that binds to the low-calcium form of the enzyme. It is selective for PAD4 over PAD1-3. GSK484 blocks the citrullination of PAD4 target proteins in human neutrophils and inhibits the formation of neutrophil extracellular traps in both mouse and human neutrophils. It exhibits favorable pharmacokinetic profiles in mouse and rat. See the Structural Genomics Consortium (SGC) website for more information.

The Uses of GSK484

GSK484 is a novel selective PAD4 inhibitor.

Biochem/physiol Actions

GSK484 is a potent selective reversible inhibitor of protein arginine deiminase PAD4, an enzyme believed to play a role in granulocyte and macrophage development leading to inflammation and immune response, and overexpressed in many tumors. GSK484 has IC50 values of 50 nM without calcium and 250 nM in the presence of 2 mM calcium. GSK484 showed minimal off-target activity tested against 50 other proteins with no activation across HDACs 1–11 even at 100 μM. GSK484 binds at a different site from the amidines, a conformation of the PAD4 active site where part of the site is reordered to form a β-hairpin. For full characterization details, please visit the GSK484 probe summary on the Structural Genomics Consortium (SGC) website.To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc

Properties of GSK484

storage temp.	2-8°C
solubility	DMSO:25.0(Max Conc. mg/mL);49.01(Max Conc. mM) Ethanol:25.0(Max Conc. mg/mL);49.01(Max Conc. mM) PBS buffer (pH 7.2):5.0(Max Conc. mg/mL);9.8(Max Conc. mM) DMF:30.0(Max Conc. mg/mL);58.82(Max Conc. mM)
form	powder
color	white to beige

Safety information for GSK484

Signal word	Warning
Pictogram(s)	Exclamation Mark Irritant GHS07
GHS Hazard Statements	H302:Acute toxicity,oral H315:Skin corrosion/irritation H319:Serious eye damage/eye irritation H335:Specific target organ toxicity, single exposure;Respiratory tract irritation
Precautionary Statement Codes	P261:Avoid breathing dust/fume/gas/mist/vapours/spray. P305+P351+P338:IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.