Applied Sciences, Vol. 14, Pages 11757: Statistical and Clustering Analysis of Safety Profiles of FDA-Approved Protein Kinase Inhibitors

Applied Sciences, Vol. 14, Pages 11757: Statistical and Clustering Analysis of Safety Profiles of FDA-Approved Protein Kinase Inhibitors

Applied Sciences doi: 10.3390/app142411757

Authors: Ioana Lavinia Radulian Georgiana Nitulescu Anca Zanfirescu George Mihai Nitulescu

Protein kinases are vital regulators in cell biology, modifying protein functions through phosphorylation. Protein kinase inhibitors (PKIs), which impede these kinases’ activities, have broadened their therapeutic scope from cancer treatment to autoimmune and viral diseases. Despite their clinical success, challenges such as drug resistance and tolerability of adverse events persist. This article used the Protein Kinase Inhibitor Database (PKIDB) and major pharmacovigilance databases to assess the adverse events (AEs) linked to FDA-approved protein kinase inhibitors. Methods were adopted to statistically identify outliers and construct a prototypical profile to generalize AE occurrences. A total of 66 inhibitors were analyzed, revealing substantial variability in the safety profiles. Cluster analysis identified distinct patterns of AEs based on kinase target classes, highlighting the importance of tailored therapeutic approaches. Statistical methods such as Tukey’s fences were used to identify drugs with unusual safety profiles, offering insights into both frequent and rare severe reactions. Real-world evidence complements clinical trial data, capturing AEs that might not be fully identified pre-approval.