GSK484 HCl exhibits strong affinity for PAD4 in its low-calcium state, with IC50s of 50 nM without calcium and 250 nM with 2 mM calcium. It also concentration-dependently inhibits PAD4's citrullination of the BAEE substrate in the presence of 0.2 mM calcium, as shown by an ammonia release assay[1].
Injections at MCAO onset, 24 h, and 48 h after occlusion, lasting for 72 hours
Evaluate the neuroprotective effects of T-GSK in TBI and MCAO models, results showed that T-GSK significantly reduced brain infarction area, brain edema, and neurological deficits, and inhibited the formation of NETs
Adv Sci (Weinh). 2024 Jun;11(21):e2308719.
Mice
Myocardial ischemia/reperfusion injury model
Intraperitoneal injection
10 mg/kg
Once daily for 3 days after surgery
To evaluate the therapeutic effect of GSK484 on myocardial ischemia/reperfusion injury, results showed that GSK484 significantly reduced myocardial damage and NETosis.
Eur Heart J. 2024 May 13;45(18):1662-1680
C57BL/6 mice
CLP-induced SAE model
Tail vein injection
4 mg/kg
Three days before and two days after CLP surgery, total 5 days
To evaluate the effect of GSK484 on neuroinflammation, BBB integrity, and cognitive function in SAE mice, results showed that GSK484 significantly reduced neuroinflammatory responses, improved BBB integrity, and enhanced cognitive function.
J Neuroinflammation. 2025 Mar 18;22(1):87
ApoE-/- mice
Experimental superficial erosion model
Systemic administration
4 mg/kg
Once daily for 7 days or three times in 7 days
To evaluate the effect of GSK484 on NET accumulation and endothelial continuity
Cardiovasc Res. 2021 Nov 22;117(13):2652-2663
ApoE−/− mice
Hyperlipidemia-associated myocardial ischemia-reperfusion injury model induced by high-cholesterol diet
Intraperitoneal injection
4 mg/kg
5 days
GSK484 significantly alleviated myocardial ischemia-reperfusion injury in hyperlipidemic mice by inhibiting neutrophil extracellular traps (NETs) release.
Adv Sci (Weinh). 2025 Mar;12(11):e2406359
BALB/c nude mice
Oesophageal squamous cell carcinoma xenograft model
4 mg/kg/2 days
14 days
Evaluate the effect of GSK484 on tumour growth and cisplatin resistance in oesophageal squamous cell carcinoma xenograft models
Clin Transl Med. 2025 Mar;15(3):e70272
Mice
4NQO-induced esophageal squamous cell carcinoma model
Intraperitoneal injection
4 mg/kg body weight
Twice weekly for 4 weeks
Evaluate the effect of GSK484 on tumor growth, results showed significant reduction in tumor numbers and sizes
J Immunother Cancer. 2024 May 9;12(5):e008662
Mice
Type 2 diabetes model
Intraperitoneal injection
4 mg/kg
Daily for 4 weeks
Inhibition of NETosis, reduction of intestinal neutrophil infiltration, and slowing of diabetic retinopathy progression
Diabetologia. 2025 Apr;68(4):866-889
Mice
D-GalN/LPS-induced acute liver failure model
Intraperitoneal injection
20 mg/kg body weight
Single dose, 24 hours before ALF induction
Significantly attenuated liver necrosis and neutrophil infiltration, reduced ALT and AST levels, and improved survival rate
In a study to determine if PAD4 inhibition could mitigate cancer-related kidney damage, MMTV-PyMT mice received daily treatments of GSK484 HCl at 4 mg/kg for a week. This treatment reduced the number of neutrophils undergoing NETosis in the blood of cancerous mice and significantly lowered the total protein in their urine, indicating improved kidney health. The same dosage of GSK484 HCl reversed kidney dysfunction indicators in tumor-bearing mice as effectively as DNase I treatment, with no observed toxicity[2].
搜索
