GSK484 hydrochloride

Name: GSK484 hydrochloride
Brand: MedChemExpress
SKU: HY-100514
Rating: 5.0 (22 reviews)

Cat. No.: HY-100514 Purity: 99.72%: FAQs
Data Sheet SDS COA Handling Instructions

Molarity Calculator

GSK484 hydrochloride is a selective and reversible peptidylarginine deiminase 4 (PAD4) inhibitor. GSK484 hydrochloride demonstrates high affinity binding to PAD4 with IC₅₀s of 50 nM in the absence of Calcium. In the presence of 2 mM Calcium, notably lower potency (250 nM) is observed.

For research use only. We do not sell to patients.

GSK484 hydrochloride Chemical Structure

CAS No. : 1652591-81-5

Size	Price	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	USD 213	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	USD 213	In-stock	Estimated Time of Arrival: December 31
Solid
1 mg	USD 76	In-stock	Estimated Time of Arrival: December 31
5 mg	USD 190	In-stock	Estimated Time of Arrival: December 31
10 mg	USD 290	In-stock	Estimated Time of Arrival: December 31
25 mg	USD 590	In-stock	Estimated Time of Arrival: December 31
50 mg		Get quote
100 mg		Get quote

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Customer Review

Based on 22 publication(s) in Google Scholar

22 Publications Citing Use of MCE GSK484 hydrochloride

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Biological Activity
Protocol
Purity & Documentation
References
Customer Review

Description

IC₅₀ & Target

IC50: 50 nM (PAD4, in the absence of Calcium), 250 nM (PAD4, in the presence of 2 mM Calcium)^[1]

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, as detected using an NH₃ release assay^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

To address whether PAD4 inhibition can suppress cancer-associated kidney injury, MMTV-PyMT mice are treated with the PAD4 inhibitor GSK484 at 4 mg/kg daily for one week. This dose suppress the elevated number of neutrophils undergoing NETosis in peripheral blood in mice with cancer. In parallel, the total protein level in urine from MMTV-PyMT mice is significantly reduced compared with untreated tumor-bearing mice, further supporting an improved functional status of the kidneys after GSK484 treatment. Administration of GSK484 at a dose of 4 mg/kg daily during one week reverts signs of kidney dysfunction in tumor-bearing mice to the same extent as DNase I treatment, without any detectable signs of toxicity^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Molecular Weight

510.03

Formula

C₂₇H₃₂ClN₅O₃

CAS No.

1652591-81-5

Appearance

Solid

Color

White to light yellow

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

4°C, stored under nitrogen, away from moisture

*In solvent : -80°C, 1 year; -20°C, 6 months (stored under nitrogen, away from moisture)

Solvent & Solubility

In Vitro:

DMSO : 125 mg/mL (245.08 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

H₂O : 100 mg/mL (196.07 mM; Need ultrasonic)

Preparing
Stock Solutions

Concentration Solvent Mass	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

View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months (stored under nitrogen, away from moisture). When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

Molarity Calculator
Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (4.08 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (4.08 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.08 mg/mL (4.08 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.

For the following dissolution methods, please prepare the working solution directly. It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: PBS
Solubility: 50 mg/mL (98.03 mM); Clear solution; Need ultrasonic
Protocol 2

Add each solvent one by one: Saline
Solubility: 100 mg/mL (196.07 mM); Clear solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Calculation results:

Working solution concentration: mg/mL

This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only.If necessary, please contact MedChemExpress (MCE).

Purity & Documentation

Purity: 99.72%

Select Batch:

Data Sheet (280 KB) SDS (393 KB)

COA (250 KB) HNMR (276 KB) LCMS (267 KB)

Handling Instructions (2659 KB)

References

[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. [Content Brief]

[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. [Content Brief]

Kinase Assay ^[1]	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 K_ds for each calcium concentration are determined using a single site saturation curve. For IC₅₀ determination, test compounds (e.g., GSK484) are 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 K_d 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]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay ^[1]	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 anti-modified citrulline antibody. FLAG-PAD constructs are detected using anti-FLAG antibody^[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration ^[2]	Mice^[2] The study includes two transgenic mouse models, 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]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.
References	[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. [Content Brief] [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. [Content Brief]

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg

H₂O / DMSO	1 mM	1.9607 mL	9.8033 mL	19.6067 mL	49.0167 mL
	5 mM	0.3921 mL	1.9607 mL	3.9213 mL	9.8033 mL
	10 mM	0.1961 mL	0.9803 mL	1.9607 mL	4.9017 mL
	15 mM	0.1307 mL	0.6536 mL	1.3071 mL	3.2678 mL
	20 mM	0.0980 mL	0.4902 mL	0.9803 mL	2.4508 mL
	25 mM	0.0784 mL	0.3921 mL	0.7843 mL	1.9607 mL
	30 mM	0.0654 mL	0.3268 mL	0.6536 mL	1.6339 mL
	40 mM	0.0490 mL	0.2451 mL	0.4902 mL	1.2254 mL
	50 mM	0.0392 mL	0.1961 mL	0.3921 mL	0.9803 mL
	60 mM	0.0327 mL	0.1634 mL	0.3268 mL	0.8169 mL
	80 mM	0.0245 mL	0.1225 mL	0.2451 mL	0.6127 mL
	100 mM	0.0196 mL	0.0980 mL	0.1961 mL	0.4902 mL

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.