GSK484 hydrochloride |
| Catalog No.GC19184 |
GSK484 is a selective PAD4 inhibitor, has been used as an anti-ischemic compound and exerts inhibitory activity against PAD4.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1652591-81-5
Sample solution is provided at 25 µL, 10mM.
GSK484 is a selective PAD4 inhibitor, has been used as an anti-ischemic compound and exerts inhibitory activity against PAD4. In the absence of calcium the IC50 value is 50 nM[1-2].
GSK484(25 nM; 1 h before irradiation) facilitated Triple-negative breast cancer (TNBC) cell apoptosis[3]. GSK484(100 nM; 15min) treatment promoted the radiosensitivity of CRC cells and induced cell death by promoting DNA double-strand breaks[4].
GSK484(4 mg/kg; i.p;40days) significantly inhibited tumor size, tumor weight and tumor volume in mice following irradiation in Nasopharyngeal carcinoma (NPC) mice model[5]. GSK484(4 mg/kg; i.p;3days) inhibits PAD4 to reduce distal lung injury by reducing neutrophil infiltration, neutrophil extracellular trap formation, apoptosis, and inflammatory cytokine secretion in mice ischemia reperfusion (IR) model[6].
References:
[1]. Perdomo J, Leung HHL, et,al. Neutrophil activation and NETosis are the major drivers of thrombosis in heparin-induced thrombocytopenia. Nat Commun. 2019 Mar 21;10(1):1322.
[2]. Du M, Yang W, et,al. Inhibition of peptidyl arginine deiminase-4 protects against myocardial infarction induced cardiac dysfunction. Int Immunopharmacol. 2020 Jan;78:106055.
[3]. Wei L, Wang X, et,al. The PAD4 inhibitor GSK484 enhances the radiosensitivity of triple-negative breast cancer. Hum Exp Toxicol. 2021 Jul;40(7):1074-1083. Erratum in: Hum Exp Toxicol. 2021 Nov;40(11):2022.
[4]. Wang B, Su X, et,al. GSK484, an inhibitor of peptidyl arginine deiminase 4, increases the radiosensitivity of colorectal cancer and inhibits neutrophil extracellular traps. J Gene Med. 2023 Sep;25(9):e3530.
[5]. Chen H, Luo M, et,al. Inhibition of PAD4 enhances radiosensitivity and inhibits aggressive phenotypes of nasopharyngeal carcinoma cells. Cell Mol Biol Lett. 2021 Mar 16;26(1):9.
[6]. Du M, Yang L, et,al. Inhibition of Peptidyl Arginine Deiminase-4 Prevents Renal Ischemia-Reperfusion-Induced Remote Lung Injury. Mediators Inflamm. 2020 Dec 29;2020:1724206.
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Fluorescence Polarization (FP) binding affinity studies [1]: |
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Preparation method |
PAD4 was serially diluted in the presence of 10 nM GSK484 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 mM, 0.2 mM, 2 mM and 10 mM). Following incubation for 50 min, apparent Kd values for each calcium concentration were determined using a single site saturation curve. For IC50 determination, test compounds were 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 GSK484 in the same assay buffer and volume. Reactions were incubated for 50 min, after which IC50 values were calculated. |
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Applications |
GSK484 demonstrated high affinity binding to the low-calcium form of PAD4 with IC50 50 nM(no Ca+). |
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Cell experiment [2]: |
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Cell lines |
MDA-MB-231 cells (Triple-negative breast cancer (TNBC)) |
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Preparation method |
GSK484 was dissolved in DMSO. The DMSO concentration of the solution used was consistently lower than 0.1%. Cells were grown to 70% -80% confluence on plates and cultivated with a low dose of GSK484 for 1 h before irradiation. |
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Reaction Conditions |
25 nM; 1 h before irradiation |
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Applications |
GSK484 facilitates cell apoptosis and promotes the radiosensitivity of MDA-MB-231 cells. |
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Animal experiment [2]: |
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Animal models |
Female BALB/c mice (6-week-old) |
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Preparation method |
MDA-MB-231 cells were injected subcutaneously into the 4th mammary fat pads of lactiferous ducts the in mice. Mice were randomly divided into four groups (Vehicle, 15 Gy alone, GSK484 4 mg/kg, and 15 Gy + GSK484 4 mg/kg). GSK484 was administered at a dose of 4 mg/kg ip in 2-hydroxypropyl-β-cyclodextrin at 1 hour before irradiation. The tumor areas were irradiated with 6 MV X-rays (15 Gy in one fraction) in 15 Gy alone and 15 Gy + GSK484 4 mg/kg groups. |
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Dosage form |
4 mg/kg; i.p.; 1 hour before irradiation |
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Applications |
Treatment with GSK484 and ischemia reperfusion (IR), the tumor volume and body weight of mice decreased significantly. |
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References: [1]. Lewis HD, Liddle J, et,al. Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation. Nat Chem Biol. 2015 Mar;11(3):189-91. doi: 10.1038/nchembio.1735. Epub 2015 Jan 26. PMID: 25622091; PMCID: PMC4397581. |
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| Cas No. | 1652591-81-5 | SDF | |
| Canonical SMILES | O=C(N1C[C@H](N)[C@H](O)CC1)C2=CC(OC)=C3C(N=C(C(N4CC5CC5)=CC6=C4C=CC=C6)N3C)=C2.[H]Cl | ||
| Formula | C27H32ClN5O3 | M.Wt | 510.03 |
| Solubility | DMSO : 125 mg/mL (245.08 mM; Need ultrasonic); H20 : 50 mg/mL (98.03 mM; Need ultrasonic) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9607 mL | 9.8033 mL | 19.6067 mL |
| 5 mM | 0.3921 mL | 1.9607 mL | 3.9213 mL |
| 10 mM | 0.1961 mL | 0.9803 mL | 1.9607 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 18 reference(s) in Google Scholar.)
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