GSK484 Hydrochloride 98% Pharmaceutical Intermediate CAS 1652591-81-5 high purity PAD4 inhibitor

Product Overview

GSK484 Hydrochloride is a selective and cell‑permeable inhibitor of protein arginine deiminase 4 (PAD4) with a Ki of approximately 0.5 µM. It blocks the conversion of arginine to citrulline, thereby reducing the formation of citrullinated proteins and NETosis, processes that are implicated in the pathogenesis of rheumatoid arthritis, ulcerative colitis, and other autoimmune disorders. In cellular assays, GSK484 suppresses PAD4‑mediated citrullination of histones and myeloperoxidase release from neutrophils. The compound is supplied as a white to off‑white crystalline powder, soluble in aqueous buffers, DMSO, and methanol, and is stable under recommended storage conditions. It is intended for laboratory research and in‑vitro studies only, not for human use. The molecule can be used to explore the role of PAD4 in cancer, inflammation, and epigenetic regulation. GSK484 demonstrates high selectivity over other PAD isoforms (PAD1, PAD2, PAD3) and does not show significant activity against a panel of 200 kinases at 10 µM. Pharmacokinetic studies in mice indicate a half‑life of ~2 h after intraperitoneal injection, with a clearance primarily hepatic. The inhibitor is also employed in disease models of lupus, multiple sclerosis, and type 1 diabetes to modulate immune responses. Its hydrochloride salt ensures improved solubility and stability under physiological pH. Research institutions worldwide utilize GSK484 to validate PAD4 as a therapeutic target and to screen for downstream biomarkers. The product is manufactured under strict quality control to meet research‑grade specifications.

Synthesis Process

GSK484 Hydrochloride is synthesized by a straightforward three‑step route. First, 4‑cyanophenyl isocyanate is reacted with N,N‑dimethyl‑1,3‑propanediamine in anhydrous acetonitrile at 0 °C to give the corresponding urea. Second, the resulting intermediate is purified by silica‑gel column chromatography. Finally, the free base is treated with a stoichiometric amount of HCl in isopropanol, and the resulting hydrochloride salt is isolated by filtration and dried under vacuum. The final product is obtained as a white powder with a purity >98 % (HPLC).

Quality Specifications

Appearance: grey to off‑white powder; Purity: ≥98 % by HPLC; Melting point: 195–200 °C; Water content: ≤0.5 % (Karl‑Fischer); Loss on drying: ≤1.0 %; Residual solvents: ≤0.5 % (ethanol); Heavy metals: ≤10 ppm; pH (1 % solution): 5.5–7.0; Solubility: soluble in water, methanol, DMSO; Identity: confirmed by 1H‑NMR and LC‑MS; Related substances: ≤0.5 %; Shelf life: 2 years when stored at –20 °C in sealed container.

Packaging & Storage

Store GSK484 Hydrochloride at –20 °C in a tightly sealed amber glass bottle or sealed aluminum foil pouch to protect from moisture and light. Keep the container in a dry, well‑ventilated area. Avoid repeated freeze‑thaw cycles. For long‑term storage, the product can be kept under nitrogen atmosphere. When handling, use personal protective equipment (gloves, goggles) to prevent contact with skin or eyes. The product is stable for at least 24 months under the recommended conditions.