Vipoglanstat (BI 1029539), a carboxamide, is a potent and selective, non-peptide and orally active small molecular inhibitor of human prostaglandin E synthase 1 (mPGES-1). Vipoglanstat also has anti-inflammatory activity[1][2].
Vipoglanstat significantly inhibits mPGES-1 level (IC50: about 1 nM)[3].
Vipoglanstat blocks the up-regulation of P-gp and mPGES-1 levels on glutamate-mediatedin isolated brain capillaries[3].
Vipoglanstat reduces human peripheral blood inflammatory cell migration and inflammatory mediator release[3].
Vipoglanstat (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[2].
Vipoglanstat (30 mg/kg; p.o.; 2 h, 8 h and 22 h) significantly reduces sepsis-induced BAL inflammatory cell recruitment, lung injury score and lung expression of mPGES-1 and inducible nitric oxide synthase[2].
Vipoglanstat (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.