Vipoglanstat (BI 1029539), formamide, is a potent, selective, non-peptide small molecule inhibitor of human prostaglandin E synthetase 1 (mPGES-1) with oral activity. Vipoglanstat also has anti~inflammatory activity.

Physicochemical Properties

Molecular Formula	C30H34CL2F5N5O3
Molecular Weight	678.520682811737
Exact Mass	677.195
CAS #	1360622-01-0
PubChem CID	56649447
Appearance	White to off-white solid powder
LogP	7.8
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	10
Heavy Atom Count	45
Complexity	1010
Defined Atom Stereocenter Count	0
SMILES	C1(NC2=C(Cl)C=CC(CNC(=O)C(C)(C)C)=C2Cl)N(C)C2=CC(OCC(F)F)=C(C(N[C@@H]3CC[C@@H](C(F)(F)F)CC3)=O)C=C2N=1
InChi Key	PFORUFFGGNOLPJ-FITNRVMRSA-N
InChi Code	InChI=1S/C30H34Cl2F5N5O3/c1-29(2,3)27(44)38-13-15-5-10-19(31)25(24(15)32)41-28-40-20-11-18(22(45-14-23(33)34)12-21(20)42(28)4)26(43)39-17-8-6-16(7-9-17)30(35,36)37/h5,10-12,16-17,23H,6-9,13-14H2,1-4H3,(H,38,44)(H,39,43)(H,40,41)/t16?,17-
Chemical Name	2-{2,6-dichloro-3-[(2,2- dimethylpropanamido)methyl]anilino}-6-(2,2- difluoroethoxy)-1-methyl-N-[trans-4- (trifluoromethyl)cyclohexyl]-1H-benzimidazole-5- carboxamide
Synonyms	Vipoglanstat BI-1029539 GS-248 BI 1029539 GS248 BI1029539 GS 248
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	mPGES-1 level is considerably inhibited by dipoglanstat (IC50: approximately 1 nM)[3]. The up-regulation of P-gp and mPGES-1 levels on glutamate-mediated in isolated brain capillaries is inhibited by vipoglanstat [3]. Vipoglanstat inhibits the migration of inflammatory cells in human peripheral blood as well as the release of inflammatory mediators[3].
ln Vivo	With reductions 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, dipoglanstat (30 mg/kg; ip) can lessen LPS-induced lung injury[2]. Lung injury score, mPGES-1 and inducible nitric oxide synthase lung expression, and sepsis-induced BAL inflammatory cell recruitment are all markedly reduced by dipoglanstat (30 mg/kg; po; 2 h, 8 h, and 22 h)[2]. Mice with acute sepsis who receive dipoglanstat (30 mg/kg; po; QD) also have significantly longer survival times[2].
Animal Protocol	Animal/Disease Models: LPS-induced acute lung injury models [2] Doses: 30 mg/kg Route of Administration: 30 mg/kg, ip Experimental Results: Preserved lung architecture and decreased immune cell influx into the lungs of LPS‑challenged mice. Animal/Disease Models: CLP-induced sepsis models[2] Doses: 30 mg/kg Route of Administration: 30 mg/kg, po, 2 hrs, 8 hrs and 22 hrs; 30 mg/kg, po, QD Experimental Results: Attenuated CLP‑induced lung injury and prolonging survival.
References	[1]. International Nonproprietary Names for Pharmaceutical Substances (INN). WHO Drug Information, Vol. 36, No. 2, 2022. [2]. Inhibition of microsomal prostaglandin E synthase-1 ameliorates acute lung injury in mice. [3]. Microsomal prostaglandin E 2 synthase-1 and its inhibitors: Molecular mechanisms and therapeutic significance. Pharmacol Res. 2022 Jan;175:105977.

Solubility Data

Solubility (In Vitro)

DMSO : ~150 mg/mL (~221.07 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 3.75 mg/mL (5.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 37.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.4738 mL	7.3690 mL	14.7380 mL
	5 mM	0.2948 mL	1.4738 mL	2.9476 mL
	10 mM	0.1474 mL	0.7369 mL	1.4738 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.