TABLE 3

Properties of representative inhaled, lung targeted compounds

Lung retention mechanism(s) for each compound are denoted by checkmarks.

Compound	Target	cLogP	cpKa	Lung Retention Mechanism(s)
				Dissolution-Limited	Tissue Affinity		Low Permeability	Slow Off-Rate
				Dissolution-Limited	Basic	Lipophilic	Low Permeability	Slow Off-Rate
Fluticasone propionate^{^a}	Glucocorticoid receptor	3.3	<3	✓		✓
Fluticasone furoate^{^b}	Glucocorticoid receptor	3.7	<3	✓		✓
Salmeterol Xinafoate^{^c}	β2-adrenergic receptor	4.1	9.4	✓	✓	✓		✓^{^d}
Salbutamol^{^e}	β2-adrenergic receptor	0.6	9.4		✓
Tiotropium bromide^{^f}	Muscarinic receptors (M3, M1)	−2.3	<3				✓	✓
Compound 3.05^{^g}	Epithelial sodium channel	−2.0	8.5		✓		✓
GSK2269557/Nemiralisib^{^h}	PI3Kδ	4.8	8.7, 4.1		✓	✓

↵^a Crim et al. (2001).
↵^b Daley-Yates (2015).
↵^c Anderson et al. (1994).
↵^d Apparent slow off-rate likely due to partitioning into lipid membrane bilayers.
↵^e Anderson et al. (1994), Dickson et al. (2016), and references therein.
↵^f Mundy and Kirkpatrick (2004), Eriksson et al. (2018).
↵^g Kley et al. (2016).
↵^h Down et al. (2015).