Compound | Target | cLogP | cpKa | Lung Retention Mechanism(s) | ||||
---|---|---|---|---|---|---|---|---|
Dissolution-Limited | Tissue Affinity | Low Permeability | Slow Off-Rate | |||||
Basic | Lipophilic | |||||||
Fluticasone propionatea | Glucocorticoid receptor | 3.3 | <3 | ✓ | ✓ | |||
Fluticasone furoateb | Glucocorticoid receptor | 3.7 | <3 | ✓ | ✓ | |||
Salmeterol Xinafoatec | β2-adrenergic receptor | 4.1 | 9.4 | ✓ | ✓ | ✓ | ✓d | |
Salbutamole | β2-adrenergic receptor | 0.6 | 9.4 | ✓ | ||||
Tiotropium bromidef | Muscarinic receptors (M3, M1) | −2.3 | <3 | ✓ | ✓ | |||
Compound 3.05g | Epithelial sodium channel | −2.0 | 8.5 | ✓ | ✓ | |||
GSK2269557/Nemiralisibh | 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).