Comparative Assessment of Protein Kinase Inhibitors in Public Databases and in PKIDB.

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Colin BournezPascal Bonnet

Abstract

Since the first approval of a protein kinase inhibitor (PKI) by the Food and Drug Administration (FDA) in 2001, 55 new PKIs have reached the market, and many inhibitors are currently being evaluated in clinical trials. This is a clear indication that protein kinases still represent major drug targets for the pharmaceutical industry. In a previous work, we have introduced PKIDB, a publicly available database, gathering PKIs that have already been approved (Phase 4), as well as those currently in clinical trials (Phases 0 to 3). This database is updated frequently, and an analysis of the new data is presented here. In addition, we compared the set of PKIs present in PKIDB with the PKIs in early preclinical studies found in ChEMBL, the largest publicly available chemical database. For each dataset, the distribution of physicochemical descriptors related to drug-likeness is presented. From these results, updated guidelines to prioritize compounds for targeting protein kinases are proposed. The results of a principal component analysis (PCA) show that the PKIDB dataset is fully encompassed within all PKIs found in the public database. This observation is reinforced by a principal moments of inertia (PMI) analysis of all molecules. I...Continue Reading

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Citations

Oct 22, 2020·Nucleic Acids Research·Georgi K KanevAlbert J Kooistra
Dec 2, 2020·International Journal of Molecular Sciences·Linda HeintzeChristian Peifer
Jan 30, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Robert Roskoski
Jan 31, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Koji Umezawa, Isao Kii
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yan ZhuXiche Hu
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Eleanor L AtkinsonDavid R Spring
Jul 25, 2021·International Journal of Molecular Sciences·Julie A Tucker, Mathew P Martin
Aug 8, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Augustine A AhmaduStéphane Bach

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Methods Mentioned

BETA
PCA

Software Mentioned

matplotlib
RDKit
Rational Discovery Kit
ChEMBL
PKIDB
PKI
Prince
PCA
Scikit
learn

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