Vipoglanstat

Vipoglanstat (BI 1029539, GS-248), a carboxamide, is a potent and selective, non-peptide and orally active small molecular inhibitor of human prostaglandin E synthase 1 (mPGES-1). Vipoglanstat (BI 1029539, GS-248) also has anti-inflammatory activity[1][2].

Research Areas >> Infection

Signaling Pathways >> Immunology/Inflammation >> PGE synthase

Vipoglanstat (BI 1029539, GS-248) significantly inhibits mPGES-1 level (IC50: about 1 nM) in isolated brain capillaries from transgenic human-mPGES-1 mice. Vipoglanstat (BI 1029539, GS-248) blocks the up-regulation of P-gp and mPGES-1 levels on glutamate-mediatedin isolated brain capillaries. Vipoglanstat (BI 1029539, GS-248) reduces human peripheral blood inflammatory cell migration and inflammatory mediator release[3].

Vipoglanstat (BI 1029539, GS-248) (30 mg/kg; i.p.) can reduce LPS-induced lung injury, with reduction in neutrophil influx, protein content, TNF-ɑ, IL-1β and PGE2 levels in bronchoalveolar lavage (BAL), myeloperoxidase activity, expression of mPGES-1, cyclooxygenase (COX)-2 and intracellular adhesion molecule in lung tissue. Vipoglanstat (BI 1029539, GS-248) (30 mg/kg; p.o.; 2 hrs, 8 hrs and 22 hrs) significantly reduces sepsis-induced BAL inflammatory cell recruitment, lung injury score and lung expression of mPGES-1 and inducible nitric oxide synthase. Vipoglanstat (BI 1029539, GS-248) (30 mg/kg; p.o.; QD) also significantly prolongs survival of mice with severe sepsis[2]. Animal Model: LPS-induced acute lung injury models[2] Dosage: 30 mg/kg Administration: 30 mg/kg, i.p. Result: Preserved lung architecture and reduced immune cell influx into the lungs of LPS‑challenged mice. Animal Model: CLP-induced sepsis models[2] Dosage: 30 mg/kg Administration: 30 mg/kg, p.o., 2 hrs, 8 hrs and 22 hrs; 30 mg/kg, p.o., QD Result: Attenuated CLP‑induced lung injury and prolongs survival.

[1]. International Nonproprietary Names for Pharmaceutical Substances (INN). WHO Drug Information, Vol. 36, No. 2, 2022.

[2]. Malarvizhi Gurusamy, et al. Inhibition of microsomal prostaglandin E synthase-1 ameliorates acute lung injury in mice.

[3]. Yan-Yu Zhang, et al. Microsomal prostaglandin E 2 synthase-1 and its inhibitors: Molecular mechanisms and therapeutic significance. Pharmacol Res. 2022 Jan;175:105977.