Revefenacin

Research use only, not for human use.

A novel potent, long-acting, lung-selective inhaled muscarinic antagonist that has high affinity at M3 receptor.

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.

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 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.

TD 4208 | TD4208 | GSK 1160724

GPCR/G Protein

mAChR

mAChR

Inflammation/Immunology

COPD

864750-70-9

597.76

C35H43N5O4

>98% (HPLC)

DMSO : ≥ 125 mg/mL209.12 mM

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

Biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester

(-20℃)

With Ice Pack

≥ 2 years