In Search of Outliers. Mining for Protein Kinase Inhibitors Based on Their Anti-Proliferative NCI-60 Cell Lines Profile
2020
George Nicolae Daniel Ion | George Mihai Nitulescu
Protein kinases play a pivotal role in signal transduction, protein synthesis, cell growth and proliferation. Their deregulation represents the basis of pathogenesis for numerous diseases such as cancer and pathologies with cardiovascular, nervous and inflammatory components. Protein kinases are an important target in the pharmaceutical industry, with 48 protein kinase inhibitors (PKI) already approved on the market as treatments for different afflictions including several types of cancer. The present work focuses on facilitating the identification of new PKIs with antitumoral potential through the use of data-mining and basic statistics. The National Cancer Institute (NCI) granted access to the results of numerous previously tested compounds on 60 tumoral cell lines (NCI-60 panel). Our approach involved analyzing the NCI database to identify compounds that presented similar growth inhibition (GI) profiles to that of existing PKIs, but different from approved oncologic drugs with other mechanisms of action, using descriptive statistics and statistical outliers. Starting from 34,000 compounds present in the database, we filtered 400 which displayed selective inhibition on certain cancer cell lines similar to that of several already-approved PKIs.
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