PF-03715455 / Pfizer - LARVOL DELTA

Inhaled product dissolution as a predictive tool of drug bioavailability: a p38 MAPK inhibitor case study using Respicell® dissolution apparatus. (PubMed, Eur J Pharm Sci) - "The inhaled p38 α/β mitogen-activated protein kinase inhibitor PF-03715455 is an example of "inhalation by design" pharmacologically active substance which maximize pulmonary residence and local efficacy, demonstrating a slow absorption rate and a prolonged pulmonary retention...The results demonstrated a clear correlation between dissolution rate and pulmonary absorption kinetics. Overall, the study highlights the critical role of dissolution testing in predicting the in vivo behavior of poorly soluble inhaled drugs and supports the use of biologically relevant in vitro dissolution methods during early-stage formulation development."

Journal

Targeting SARS-CoV-2 nsp13 Helicase and Assessment of Druggability Pockets: Identification of Two Potent Inhibitors by a Multi-Site In Silico Drug Repurposing Approach. (PubMed, Molecules) - "Finally, by means of visual inspection analysis and based on their commercial availability, five promising compounds were submitted to in vitro assays. Among them, PF-03715455 was able to block both the unwinding and NTPase activities of nsp13 in a micromolar range."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Screening of drug databank against WT and mutant main protease of SARS-CoV-2: Towards finding potential compound for repurposing against COVID-19. (PubMed, Saudi J Biol Sci) - "While PF-03715455 (Y54C), Salvianolic acid A (N142S and T190I), and Montelukast (A191V) were found to be most active against the other selected mutants. It was also found that some other compounds such as Acteoside, 4-Amino-N- {4-[2-(2,6-Dimethyl-Phenoxy)-Acetylamino]-3-Hydroxy-1-Isobutyl-5-Phenyl-Pentyl}-Benzamide, PF-00610355, 4-Amino-N-4-[2-(2,6-Dimethyl-Phenoxy)-Acetylamino]-3-Hydroxy-1-Isobutyl-5-Phenyl-Pentyl}-Benzamide and Atorvastatin were showing high efficacy against the WT as well as other selected mutants. We believe that these molecules will provide a better and effective option for the treatment of COVID-19 clinical manifestations."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

An Evaluation Of PF-03715455 In Moderate To Severe Chronic Obstructive Pulmonary Disease (clinicaltrials.gov) - P2; N=17; Terminated; Sponsor: Pfizer; N=100 -> 17 ; Recruiting -> Terminated ; Trial primary completion date: Mar 2017 ->May 2015

Enrollment change • Trial primary completion date • Trial termination • Biosimilar • Chronic Obstructive Pulmonary Disease

Pulmonary delivery of a p38 α/β MAP kinase inhibitor: bioanalytical method validation and biodistribution in rat plasma and respiratory tissues. (PubMed, Eur J Pharm Sci) - "In conclusion, a linear, accurate, precise and reproducible method has been developed and validated according to FDA and EMA guidelines to quantify plasmatic and tissue-associated concentrations of PF-03715455 in order to investigate this compound in pharmacokinetics pre-clinical studies in rats. The administration of drug solution evidenced a prolonged permanence of the drug in the lungs that could be related to a slow absorption/poor permeability of the drug across airways epithelia."

Journal • Preclinical • Asthma • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Respiratory Diseases