| Description |
CHF-6366 is a potent M3 muscarinic antagonist and β2-adrenergic receptors agonist with pKi values of 10.4 and 11.4, respectively. CHF-6366 is also a weak calcium channel inhibitor (IC50~50 μM). CHF-6366 inhibits bronchoconstriction in guinea pigs. CHF-6366 can be used to research chronic obstructive pulmonary disease (COPD)[1].
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| Related Catalog |
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| Target |
pKi: 10.4 (M3 muscarinic receptor), 11.4 (β2-adrenergic receptors)[1] IC50: ~50 μM (calcium channel)[1]
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| In Vivo |
CHF-6366 (0.3 and 1 nM/kg; intratracheal administration; single dosage) inhibits bronchoconstriction in a dose-dependent manner[1]. CHF-6366 (500 nM/kg; intratracheal administration; single dosage) exhibits low systemic exposure and no accumulation risk[1]. Pharmacokinetic Parameters of CHF-6366 in lung and plasma of guinea pig (intratracheal administration, 500 nM/kg)[1]. Lung Plasma Cmax 28400 ng/g 126 ng/mL Tmax 0.083 h 0.083 h AUClast 460361 ng/g·h 460 ng/mL·h AUCinf 725199 ng/g·h 661 ng/mL·h half-life 49.2 h 15.4 h Animal Model: Guinea pigs[1] Dosage: 0.3 and 1 nM/kg Administration: Intratracheal administration; single dosage Result: Inhibited bronchoconstriction in a dose-dependent manner. Animal Model: Guinea pigs[1] Dosage: 500 nM/kg (Pharmacokinetic Analysis) Administration: Intratracheal administration; single dosage Result: Sustained exposure up to 72 h and the appropriate gradual decline which is suggestive of no accumulation risk. Showed very low systemic exposure.
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| References |
[1]. Carzaniga L, et al. Discovery of Clinical Candidate CHF-6366: A Novel Super-soft Dual Pharmacology Muscarinic Antagonist and β2 Agonist (MABA) for the Inhaled Treatment of Respiratory Diseases. J Med Chem. 2022 Aug 11;65(15):10233-10250.
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