DC Chemicals · Product datasheet

Ensifentrine — Datasheet

CAT. NO. DC82103

Product page and current package options

ParameterValue
Chemical NameEnsifentrine
CAS No.1884461-72-6
SynonymsEnsifentrine;RPL 554;3E3D8T1GIX;RPL554;Ensifentrine [INN];Ensifentrine [USAN];Ensifentrine (USAN/INN);BCP31840;WHO 10726;SB19810;D11743;Q7277486;9,10-Dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carba
FormulaC26H31N5O4
M.Wt477.5554
SMILESO=C1N(C([H])([H])C([H])([H])N([H])C(N([H])[H])=O)/C(/C([H])=C2C3=C([H])C(=C(C([H])=C3C([H])([H])C([H])([H])N21)OC([H])([H])[H])OC([H])([H])[H])=N/C1C(C([H])([H])[H])=C([H])C(C([H])([H])[H])=C([H])C=1C([H])([H])[H]
Purity>98%
Storage2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Biological Activity

Ensifentrine (RPL-554) is an inhaled first-in-class dual inhibitor of phosphodiesterase 3 (PDE3) and PDE4 with IC50s of 0.4 nM and 1479 nM, respectively. Ensifentrine has bronchoprotective and anti-inflammatory activities. Ensifentrine can be used for chronic obstructive pulmonary disease (COPD) research[1][2].

In Vitro

Ensifentrine (RPL-554) inhibits, in a concentration-dependent manner, lipopolysaccharide-induced TNF-α release from human monocytes (IC50 of 0.52 μM) and proliferation of human mononuclear cells to phytohemagglutinin (IC50 of 0.46 μM)[1]. Electrical field stimulation-induced contraction of guinea pig superfused isolated tracheal preparations is significantly inhibited by Ensifentrine (10 μM). Contractile responses are suppressed for up to 12 h after termination of superfusion with RPL-554 demonstrating a long duration of action[1].

In Vivo

Ensifentrine (RPL-554; 10 mg/kg; Oral administration; once) significantly inhibits eosinophil recruitment following antigen challenge in ovalbumin-sensitized guinea pigs[1]. The inhalation of dry powder containing Ensifentrine by conscious guinea pigs (25% in micronized lactose) 1.5 h before antigen exposure significantly inhibits the recruitment of eosinophils to the airways[1]. Exposure of conscious guinea pigs to inhalation of dry powder containing Ensifentrine (2.5%) in micronized lactose significantly inhibits histamine-induced plasma protein extravasation in the trachea and histamine-induced bronchoconstriction over a 5.5-h period[1]. Animal Model: Male Dunkin Hartley guinea pigs (200-300 g) injected with ovalbumin[1]. Dosage: 10 mg/kg Administration: Oral administration; once Result: Significantly inhibits eosinophil recruitment following antigen challenge in ovalbumin-sensitized guinea pigs.

Target

PDE3:0.4 nM (IC50)

PDE4:1479 nM (IC50)

References & source

[1]. Victoria Boswell-Smith, et al. The pharmacology of two novel long-acting phosphodiesterase 3/4 inhibitors, RPL554 [9,10-dimethoxy-2(2,4,6-trimethylphenylimino)-3-(n-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one] and RPL565 [6,7-dihydro-2-(2,6-diisopropylphenoxy)-9,10-dimethoxy-4H-pyrimido[6,1-a]isoquinolin-4-one]. J Pharmacol Exp Ther. 2006 Aug;318(2):840-8.

[2]. Henrik Watz, et al. Symptom Improvement Following Treatment with the Inhaled Dual Phosphodiesterase 3 and 4 Inhibitor Ensifentrine in Patients with Moderate to Severe COPD - A Detailed Analysis. Int J Chron Obstruct Pulmon Dis. 2020 Sep 16;15:2199-2206.

DC Chemicals original product information

Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.

Cart

Request quotation