Posted by Professor Wu Dianquing at Yale university has discovered that a widely used anticancer drug, pazopanib might be suitable for treating and preventing lung injuries due to or associated with viral infections, such as those due to coronaviruses that cause Severe Acute Respiratory Syndrome, including COVID-19. A recently published PCT patent application (WO2021236935) provides methods for treating or preventing the lung injuries often associated with these infections, such as acute lung injury (ALI), lung fibrosis, and acute respiratory distress syndrome (ARDS). The methods comprise administering a therapeutically effective amount of a pharmaceutical composition comprising a protein kinase inhibitor compound having MAP3K2/MAP3K3 inhibition activity, such as pazopanib.
A HPBCD-based formulation prepared in the following was tested through the experimental examples:
1 . Put 3.294 ml purified water in a small beaker with a small magnetic stir bar.
2. Weigh 1.663g 2-Hydroxypropyl-beta-cyclodextrin (HP-beta-CD).
3. Add HP-beta-CD slowly into the water while stirring.
4. Keep stirring until HP-beta-CD completely dissolved.
5. Transfer the HP-beta-CD solution into a 15ml tube.
6. Weigh 43mg pazopanib hydrochloride and add it into HP-beta-CD solution.
7. Vibrate the tube for 5min followed by 30min water bath sonication.
8. Then keep the tube in 50°C for 30 min and pazopanib hydrochloride should be completely dissolved.
3mg/kgbw pazopanib was delivered to mice via retro-orbital injection. Treatment with a pharmaceutical composition of pazopanib was shown to significantly reduce pulmonary permeability in mouse coronavirus induced acute lung injury model when 3 doses were given at 3mg/kgbw.
Professor Wu’s spinout company (Qx Therapeutics Inc.) has filed the above referenced patent and has received U.S. Food and Drug Administration authorization of “safe to proceed” with investigating their composition in a phase 2 clinical trial for patients with severe symptomatic COVID-19 Infection.
Further details may be read at the patent applicant’ homepage [1] and Professor Wu’s site [2].