Uses
Piclamilast is a potent and selective phosphodiesterase-4 (PDE4) inhibitor. Piclamilast may offer therapeutic strategies in respiratory diseases, including asthma and chronic obstructive pulmonary disease. Piclamilast may also provide a treatment option for pre-term infants with bronchopulmonary dysplasia (BPD).
Definition
ChEBI: A monocarboxylic acid amide resulting from the formal condensation of the carboxy group of 3-(cyclopentyloxy)-4-methoxybenzoic acid with the primary amino group of 3,5-dichloropyridin-4-amine.
Biological Activity
Piclamilast is a potent and selective cyclic AMP phosphodiesterase-4 inhibitor th at exhibits equal, high affinity for both the PDE4 high- and low-affinity rolipram binding states (HARBS and LARBS). Recent studies shown th at piclamilast inhibits Trypanosoma brucei PDEB1 (TbrPDEB1) and TbrPDEB2.', 'Piclamilast is also known as N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-methoxybenzamide. Piclamilast regulates the cAMP (cyclic adenosine monophosphate) signaling pathway. It increases the retinoid-dependent transactivation and the degradation of retinoic acid receptor α (RARα).
in vivo
Piclamilast (RP 73401, 10 mg/kg, 30 min) alone does not affect the MST of leukemia-bearing animals. Piclamilast combined with ATRA (HY-14649) significantly more effective than ATRA alone in increasing the MST (40 days; interval 34–45 days) of leukemia-bearing animals[3].
| Animal Model: | SCID mice[3]. |
| Dosage: | 10 mg/kg (combined with ATRA (HY-14649)). |
| Administration: | Injection daily. |
| Result: | Significantly more effective than ATRA alone in increasing the MST (40 days; interval 34–45 days) of leukemia-bearing animals. |
IC 50
PDE4: 16 nM (IC
50, in pig aorta); PDE4: 2 nM (IC
50, in eosinophil soluble); PDE1: >100 μM (IC
50); PDE2: 40 μM (IC
50); PDE3: >100 μM (IC
50); PDE5: 14 μM (IC
50)
