GSK484 hydrochloride

SKU: orb1220061

Description

GSK484 hydrochloride (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.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.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 suppresses 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. 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.

Key Properties

• CAS Number: 1652591-81-5
• MW: 510.03
• Purity: >98% (HPLC)
• Formula: C₂₇H₃₀ClN₅O₃
• SMILES: Cl.COC1=CC(=CC2=C1N(C)C(=N2)C1=CC2=CC=CC=C2N1CC1CC1)C(=O)N1CC[C@@H](O)[C@@H](N)C1
• Target: PAD4
• Solubility: DMSO:60 mg/mL (117.64 mM; Need ultrasonic)

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

GTPL8577,AOB6992

Quick Database Links

Gene Symbol

PAD4