Comparison of FDA Approved Kinase Targets to Clinical Trial Ones: Insights from Their System Profiles and Drug-Target Interaction Networks

Abstract

Kinase is one of the most productive classes of established targets, but the majority of approved drugs against kinase were developed only for cancer. Intensive efforts were therefore exerted for releasing its therapeutic potential by discovering new therapeutic area. Kinases in clinical trial could provide great opportunities for treating various diseases. However, no systematic comparison between system profiles of established targets and those of clinical trial ones was conducted. The reveal of probable difference or shift of trend would help to identify key factors defining druggability of established targets. In this study, a comparative analysis of system profiles of both types of targets was conducted. Consequently, the systems profiles of the majority of clinical trial kinases were identified to be very similar to those of established ones, but percentages of established targets obeying the system profiles appeared to be slightly but consistently higher than those of clinical trial targets. Moreover, a shift of trend in the system profiles from the clinical trial to the established targets was identified, and popular kinase targets were discovered. In sum, this comparative study may help to facilitate the identification of the druggability of established drug targets by their system profiles and drug-target interaction networks.

Performance Evaluation and Online Realization of Data-driven Normalization Methods Used in LC/MS based Untargeted Metabolomics Analysis

“…At present, the metabolomics based on liquid chromatography mass spectrometry (LC/MS) is capable of simultaneously monitoring thousands of metabolites in bio-fluid, cell and tissue, and is widely applied to various aspects of biomedical research. In particular, metabolomics analysis on LC/MS data can aid the choice of therapy2, provide powerful tools for drug discovery by revealing drug mechanism of actions and potential side effects3, and help to identify biomarkers456 of various diseases such as hepatocellular carcinoma (HCC)7, colorectal cancer8, insulin resistance9, and so on.…”

Cas-CLIP: a method for customizing pooled CRISPR libraries

“…Scalability of Cas-CLIP is essential for applications in various biological research studies. To confirm that a set of gRNAs targeting each gene could be simultaneously depleted by Cas-CLIP, we designed rc-gRNAs for 81 gRNAs targeting 27 human kinase genes, which were known to be the targets of FDA-approved drugs(Xu et al, 2016). Kinases are known to be potential therapeutic targets and their inhibitors are used as cancer-targeting agents(Wu et al, 2015).…”

Breakthroughs in modern cancer therapy and elusive cardiotoxicity: Critical research‐practice gaps, challenges, and insights

“…According to the latest reports, approximately 76 targeted anticancer drugs received approval from the US FDA from 2001 to May 2017; these drugs include small molecule kinase inhibitors, other types of agents (e.g., proteasome and histone deacetylases targeting inhibitors) (Table ), and therapeutic monoclonal antibodies (Tables and ). The clinical patterns of toxicity associated with some of these agents have been addressed or discussed in detail in other reviews .…”

“…102,111,112 Kinases comprise one of the largest classes of proteins encoded by the human genome, and their signaling molecules play an important role in regulating almost every aspect of cell function in many different tissue types and organs, 102,105,108,109 including the cell fate decisions of cardiac myocytes that lead to cardiac pathologies. 7,113 Thus, dysfunctional kinase activity disrupts the normal control of cellular phosphorylation signaling pathways and leads to numerous pathologies beyond cancer through pathway affiliation, 99 including immunological, neurological, metabolic, infectious diseases, diabetes, osteoporosis, and otology. 7,98,101,102,105,[113][114][115] Consequently, the pharmacological utility of kinase-targeting has been expanded for kinase-targeted therapies in a broad array of indications beyond cancers.…”