Navafenterol

Navafenterol, also known as AZD-8871, is a new chemical entity possessing long-acting effect in a single molecule which presents a novel treatment approach to chronic obstructive pulmonary disease [COPD] and potentially also asthma (in combination with an inhaled corticosteroid [ICS]). Mònica Aparici, et al. Pharmacological Profile of AZD8871 (LAS191351), a Novel Inhaled Dual M3 Receptor Antagonist/ β 2-Adrenoceptor Agonist Molecule with Long-Lasting Effects and Favorable Safety Profile. J Pharmacol Exp Ther. 2019 Jul;370(1):127-136.

Product information

CAS Number: 1435519-06-4

Molecular Weight: 742.91

Formula: C38H42N6O6S2

Chemical Name: Navafenterol

Smiles: CN(CCCN1N=NC2=CC(CNC[C@H](O)C3=CC=C(O)C4NC(=O)C=CC3=4)=CC=C12)[C@@H]1CC[C@H](CC1)OC(=O)C(O)(C1=CC=CS1)C1=CC=CS1

InChiKey: ZNKWRAKPQQZLNX-ZDQHWEPJSA-N

InChi: InChI=1S/C38H42N6O6S2/c1-43(25-8-10-26(11-9-25)50-37(48)38(49,33-5-2-19-51-33)34-6-3-20-52-34)17-4-18-44-30-14-7-24(21-29(30)41-42-44)22-39-23-32(46)27-12-15-31(45)36-28(27)13-16-35(47)40-36/h2-3,5-7,12-16,19-21,25-26,32,39,45-46,49H,4,8-11,17-18,22-23H2,1H3,(H,40,47)/t25-,26-,32-/m0/s1

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: To be determined

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

The pIC50 values of Navafenterol (AZD-8871) at the human M1, M2, M3, M4, and M5 receptor are 9.9, 9.9, 9.5, 10.4, and 8.8, respectively. pEC50 values of Navafenterol at theβ1, β2, and β3 adrenoceptor are 9.0, 9.5, and 8.7, respectively. It is selective for the β2-adrenoceptor over the β1 and β3 subtypes (3- and 6-fold, respectively). Navafenterol shows kinetic selectivity for the M3 (half-life: 4.97 hours) over the M2 receptor (half-life: 0.46 hour). Navafenterol shows dual antimuscarinic and β2-adrenoceptor functional activity in isolated guinea pig tissue (pIC50 in electrically stimulated trachea: 8.6; pEC50 in spontaneous tone isolated trachea: 8.8, respectively), which are sustained over time.

In Vivo:

Navafenterol (AZD-8871) prevents acetylcholine-induced bronchoconstriction in both guinea pig and dog with minimal effects on salivation and heart rate at doses with bronchoprotective activity. Moreover, AZD8871 shows long-lasting effects in dog, with a bronchoprotective half-life longer than 24 hours. Navafenterol shows dose-proportional bronchoprotective effect, with a nonsignificantly different potency (ID40 of 0.40 µg/kg).

References:

1. Singh D, Fuhr R, Jimenez L, Wählby Hamrén U, Jauhiainen A, Malice MP, Balaguer V, Lei A, Aggarwal A, Astbury C, Psallidas I. A Randomized Trial of Dual-Acting Bronchodilator AZD8871 for Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2019 May 15;199(10):1282-1284. doi: 10.1164/rccm.201812-2345LE. PubMed PMID: 30768909
2. Aparici M, Carcasona C, Ramos I, Montero JL, Otal R, Ortiz JL, Cortijo J, Puig C, Vilella D, De Alba J, Doe C, Gavaldà A, Miralpeix M. Pharmacological Profile of AZD8871 (LAS191351), a Novel Inhaled Dual M(3) Receptor Antagonist/β (2)-Adrenoceptor Agonist Molecule with Long-Lasting Effects and Favorable Safety Profile. J Pharmacol Exp Ther. 2019 Jul;370(1):127-136. doi: 10.1124/jpet.118.255620. Epub 2019 May 13. PubMed PMID: 31085697.

Products are for research use only. Not for human use.