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GSK484 hydrochloride

Catalog No. TQ0067 CAS 1652591-81-5

Synonyms: GTPL8577, AOB6992

GSK484 hydrochloride (GTPL8577) (GTPL8577) is a specifc and reversible peptidyl arginine deiminase 4 (PAD4) inhibitor. It demonstrates high-affinity binding to PAD4 with IC50s of 50 nM in the absence of Calcium.

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GSK484 hydrochloride, CAS 1652591-81-5

Pack Size	Availability	Price/USD
1 mg	In stock	$ 68.00
5 mg	In stock	$ 158.00
10 mg	In stock	$ 239.00
25 mg	In stock	$ 482.00
50 mg	In stock	$ 689.00
100 mg	In stock	$ 982.00
1 mL * 10 mM (in DMSO)	In stock	$ 176.00

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Purity: 99.62%

Purity: 99.51%

Purity: 99.42%

Purity: 99.36%

Biological Description

Chemical Properties

Storage & Solubility Information

Description	GSK484 hydrochloride (GTPL8577) (GTPL8577) is a specifc and reversible peptidyl arginine deiminase 4 (PAD4) inhibitor. It demonstrates high-affinity binding to PAD4 with IC50s of 50 nM in the absence of Calcium.
Targets&IC50	PAD4:50 nM (in 0 mM Calcium), PAD4:50 nM (in 2 mM Calcium)
In vitro	GSK484 demonstrates high-affinity binding to the low-calcium form of PAD4 with IC50s of 50 nM and 250 nM in the absence of Calcium (0 mM) and Calcium (2 mM), respectively. GSK484 also inhibits PAD4 citrullination (at 0.2 mM Calcium) of benzoyl-arginine ethyl ester (BAEE) substrate in a concentration-dependent manner [1].
In vivo	To determine if PAD4 inhibition can mitigate cancer-associated kidney damage, MMTV-PyMT mice received the PAD4 inhibitor GSK484 at a dosage of 4 mg/kg daily for one week. This treatment effectively lowered the elevated neutrophil NETosis in the peripheral blood of cancerous mice. Concurrently, there was a significant reduction in the urine protein level of treated MMTV-PyMT mice compared to those untreated, indicating kidney function improvement akin to that achieved with DNase I treatment, without any observed toxicity [2].
Kinase Assay	PAD4 is serially diluted in the presence of 10 nM GSK215 in assay buffer (100 mM HEPES, pH 8, 50 mM NaCl, 5% glycerol, 1 mM CHAPS, 1 mM DTT) at varying concentrations of calcium (0, 0.2, 2 and 10 mM). Following incubation for 50 min, apparent Kds for each calcium concentration are determined using a single site saturation curve. For IC50 determination, GSK484 is serially diluted in DMSO (1% final assay concentration) and tested at the same range of calcium concentrations in the presence of PAD4 (at the calculated Kd for each calcium condition) and 10 nM GSK215 in the same assay buffer and volume. Reactions are incubated for 50 min after which IC50 values are calculated using a four-parameter logistic equation [1].
Cell Research	HEK293 cells stably expressing N-terminal FLAG-tagged PAD1, PAD2, PAD3 or PAD4 are engineered by retroviral transduction. Cells are grown in 15 cm diameter plates to subconfluency in DMEM supplemented with 10% Foetal Bovine Serum, harvested by centrifugation and washed once in PBS/2 mM EGTA. Cells are lysed in 50 mM Tris-Cl, pH 7.4, 1.5 mM MgCl2, 5% glycerol, 150 mM NaCl, 25 mM NaF, 1 mM Na3VO4, 0.4% NP40, 1 mM DTT with protease inhibitors. Lysates are pre-incubated for 20 min at 4°C with DMSO alone (2%), 100 μM of GSK199, GSK484, GSK106 or 200 μM Cl-amidine. Citrullination reactions are performed for 30 min at 37°C in the presence of 2 mM calcium. Extracts are loaded on to gels, proteins separated by SDS-PAGE and transferred to PVDF membranes. Citrullinated proteins are then chemically modified and detected using an anti-modified citrulline antibody. FLAG-PAD constructs are detected using the anti-FLAG antibody [1].
Animal Research	The study includes the MMTV-PyMT mouse model for mammary carcinoma (FVB/n background) and the RIP1-Tag2 mouse model for pancreatic neuroendocrine carcinoma (C57BL/6 background). Mice are treated daily by intra-peritoneal injections of the PAD4 inhibitor GSK484 (4 mg/kg). GSK484 is dissolved in 99.9% ethanol at a concentration of 25 mg/mL to generate a stock solution and further diluted 1:50 in 0.9% NaCl shortly before injection of 200 μL/mouse [2].

Synonyms	GTPL8577, AOB6992
Molecular Weight	510.03
Formula	C27H32ClN5O3
CAS No.	1652591-81-5

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

DMSO: 60 mg/mL (117.64 mM), Sonication is recommended.

References and Literature

1. Lewis HD, et al. Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation. Nat Chem Biol. 2015 Mar;11(3):189-91. 2. Cedervall J, et al. Pharmacological targeting of peptidylarginine deiminase 4 prevents cancer-associated kidney injury in mice. Oncoimmunology. 2017 Apr 20;6(8):e1320009.

Citations

1. Chen J, Zhao L, Ding X, et al. Aβ1–40 Oligomers Trigger Neutrophil Extracellular Trap Formation through TLR4- and NADPH Oxidase-Dependent Pathways in Age-Related Macular Degeneration. Oxidative Medicine and Cellular Longevity. 2022

Related compound libraries

This product is contained In the following compound libraries：

Inhibitor Library Epigenetics Compound Library Bioactive Compounds Library Max Bioactive Compound Library Immunology/Inflammation Compound Library NO PAINS Compound Library

Related Products

Related compounds with same targets

N-[1-(Aminocarbonyl)-4-[(2-chloro-1-iminoethyl)amino]butyl]benzamide BMS-P5 free base Cl-amidine hydrochloride Acefylline BMS-P5 GSK121 GSK199

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Keywords

GSK484 hydrochloride 1652591-81-5 Chromatin/Epigenetic PAD GTPL8577 AOB6992 GSK 484 Protein Arginine Deiminase GTPL-8577 GSK484 Hydrochloride GTPL 8577 GSK-484 AOB-6992 GSK-484 hydrochloride GSK484 inhibit Peptidylarginine Deiminase GSK 484 Hydrochloride AOB 6992 Inhibitor GSK-484 Hydrochloride inhibitor

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