Method of preventing or treating a pulmonary disease or condition
A pharmaceutical composition for aerosol administration and method of preventing or treating a pulmonary disease or condition in a subject with a SphK1 inhibitor are provided.
1. A method of treating a pulmonary disease or condition in a subject comprising administering to a subject in need of treatment an effective amount of a SphK1 inhibitor to treat the subject's pulmonary disease or condition, wherein the SphK1 inhibitor
(a) exhibits at least a 20-fold greater selectivity for SphK1than SphK2; and
(b) is cell permeable, has an IC 50 value of less than 10 μM, or has a K i of less than 10 μM, or a combination thereof.
2. The method of claim 1 , wherein the pulmonary disease or condition comprises pulmonary hypertension, adult respiratory distress syndrome, restrictive lung disease, chronic obstructive pulmonary disease, bronchiectasis, bronchiolectasis, bronchiolitis, bronchitis, emphysema, a diffuse interstitial or infiltrative lung disease, serofibrinous pleuritis, suppurative pleuritis, hemorrhagic pleuritis, a pleural effusion, idiopathic pulmonary fibrosis, bronchopulmonary dysplasia, hyperoxia or oxygen-induced lung injury, injury due to drug or chemotherapeutic toxicity, radiation-induced injury, or chemical injury.
3. The method of claim 1 , wherein the SphK1 inhibitor comprises [(2R)-1-[[4-[[3-(benzenesulfonyl methyl)-5-methylphenoxy]methyl]phenyl] methyl] pyrrolidin-2-yl] methanol (PF-543) or a pharmaceutically acceptable salt thereof.
4. The method of claim 3 , wherein the pharmaceutically acceptable salt is a citric acid salt.
5. The method of claim 1 , wherein said SphK1 inhibitor is administered to the lungs of the subject.
6. A method of treating a pulmonary disease or condition in a subject comprising administering to a subject in need of treatment an effective amount of [(2R)-1-[[4-[[3-(benzenesulfonyl methyl)-5-methylphenoxy]methyl]phenyl]methyl] pyrrolidin-2-yl] methanol (PF-543), or a pharmaceutically acceptable salt thereof, to treat the subject's pulmonary disease or condition, wherein the pulmonary disease or condition comprises restrictive lung disease, bronchiectasis, bronchiolectasis, bronchitis, emphysema, a diffuse interstitial lung disease, a diffuse infiltrative lung disease, serofibrinous pleuritis, suppurative pleuritis, hemorrhagic pleuritis, idiopathic pulmonary fibrosis, bronchopulmonary dysplasia, hyperoxia or oxygen-induced lung injury, injury due to drug or chemotherapeutic toxicity, radiation-induced injury, or chemical injury.
7. The method of claim 6 , wherein the pharmaceutically acceptable salt is a citric acid salt.
8. The method of claim 6 , wherein said SphK1 inhibitor is administered to the lungs of the subject.