PL-3994 

PL-3994 is a natriuretic peptide receptor-A (NPR-A) agonist that is resistant to neutral endopeptidase and acts as a bronchodilator. PL-3994 produces concentration-dependent relaxation of pre-contracted guinea-pig trachea with an IC₅₀ value of 42.7 nM^[1].

PL-3994 has high affinity for recombinant human, dog, or rat NPR-As with K_i values of 1 nM, 41 nM, 10 nM, respectively. And PL-3994 binds to hNPR-C with K_i of 7 nM, while there is no effect on cGMP generation in hNPR-B^[1].
PL-3994 induces dose-dependent cGMP generation in human, dog, and rat NPR-As with EC₅₀s of 2 nM, 3 nM, and 14 nM, respectively^[1].
PL-3994 (0.1 nM-100 mM; 5-20 min) elicits a potent, concentration-dependent but small relaxation of pre-contracted human precision-cut lung slices (hPCLS)^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Intratracheal PL-3994 (1-1000 mg/kg; i.t.; single dose) produces a dose-dependent inhibition of the bronchoconstrictor response evoked by aerosolized methacholine, without significant effect on cardiovascular parameters^[1].
PL-3994 is resistant to degradation by human neutral endopeptidase (hNEP) (92% remaining after 2 h), whereas the natural ligands, ANP and CNP, are rapidly metabolized (≤1% remaining after 2 h)^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

1875.18

C₈₂H₁₂₇N₂₇O₂₀S₂

952295-80-6

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Edelson JD, et al. In vitro and in vivo pharmacological profile of PL-3994, a novel cyclic peptide (Hept-cyclo(Cys-His-Phe-d-Ala-Gly-Arg-d-Nle-Asp-Arg-Ile-Ser-Cys)-Tyr-[Arg mimetic]-NH(2)) natriuretic peptide receptor-A agonist that is resistant to neutral endopeptidase and acts as a bronchodilator. Pulm Pharmacol Ther. 2013 Apr;26(2):229-38.  [Content Brief]