Revefenacin

SKU: orb1223819

Description

A novel potent, long-acting, lung-selective inhaled muscarinic antagonist that has high affinity at M3 receptor, demonstrates in vitro kinetic selectivity for M3 over M2 and no meaningful off-target activity; produces sustained inhibition of acetylcholine-induced bronchoconstriction for up to 24 hours along with tiotropium and glycopyrronium, has the potential to be a long-acting bronchodilator for once-daily treatment of respiratory diseases.COPD Phase 3 Clinical(In Vitro):The Kis of revefenacin are 0.42, 0.32, 0.18, 0.56, and 6.7 nM at human M1, M2, M3, M4 and M5 receptors, respectively. In a functional assay, revefenacin is shown to be a functional antagonist with inhibition constants similar to binding Ki's. Revefenacin also inhibits agonist-induced contraction of guinea pig isolated tracheal ring preparation with an affinity of 0.1 nM, similar to the measured M3 biding Ki.(In Vivo):In anesthetized dogs, revefenacin, along with tiotropium and glycopyrronium, produce sustained inhibition of acetylcholine-induced bronchoconstriction for up to 24 hours. In anesthetized rats, inhaled revefenacin exhibits dose-dependent 24-hour bronchoprotection against methacholine-induced bronchoconstriction. The estimated 24-hour potency is 45.0 μg/mL and the bronchoprotective potencies are maintained after 7 days of once-daily dosing.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 864750-70-9
• MW: 597.76
• Purity: >98% (HPLC)
• Formula: C₃₅H₄₃N₅O₄
• SMILES: O=C(OC1CCN(CCN(C)C(C2=CC=C(CN3CCC(C(N)=O)CC3)C=C2)=O)CC1)NC4=CC=CC=C4C5=CC=CC=C5
• Target: mAChR
• Solubility: DMSO : ≥ 125 mg/mL209.12 mM

Bioactivity

• In Vivo:
  In anesthetized dogs, revefenacin, along with tiotropium and glycopyrronium, produce sustained inhibition of acetylcholine-induced bronchoconstriction for up to 24 hours. In anesthetized rats, inhaled revefenacin exhibits dose-dependent 24-hour bronchoprotection against methacholine-induced bronchoconstriction. The estimated 24-hour potency is 45.0 μg/mL and the bronchoprotective potencies are maintained after 7 days of once daily dosing.
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• In Vitro:
  The Kis of revefenacin are 0.42, 0.32, 0.18, 0.56, and 6.7 nM at human M1, M2, M3, M4 and M5 receptors, respectively. In a functional assay, revefenacin is shown to be a functional antagonist with inhibition constants similar to binding Ki's. Revefenacin also inhibits agonist-induced contraction of guinea pig isolated tracheal ring preparation with an affinity of 0.1 nM, similar to the measured M3 biding Ki.
  Read more...

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

TD 4208 | TD4208 | GSK 1160724

Quick Database Links

Gene Symbol

mAChR