Background: During lead identification and optimization, the advancement criteria may be driven based on scientific principles, prior experiences, and/or by examining the path paved by approved drugs. However, accessing the discovery data on physicochemical and ADME properties of the approved kinase inhibitors is a monumental task as these are either scattered in the literature or have not been published. Objective: Our goals were: 1) To compile the relevant data on all kinase inhibitors approved prior to 2016 for easy access by the biopharmaceutical community, 2) To provide a retrospective analysis to highlight trends and attributes which may have contributed to the “developability” of these drugs, and 3) To ignite focused debates on what constitutes “actionable”, “nice-to-have”, and unnecessary data. Such debates bring about more clarity on stage appropriateness of different types of information and prevent confusion due to abundance of unnecessary data, leading to more efficient and less costly drug discovery programs. Methods: A careful and thorough analysis of different bodies of data such as published manuscripts, and available regulatory documents were employed. Results: We were able to assemble a large body of data on the first thirty kinase inhibitors approved by US FDA since 2001. Conclusion: In conclusion, we have compiled physicochemical and ADME data on the first 30 approved kinase inhibitors and provided our retrospective analysis, which we hope is helpful in constructing advancement criteria in discovery programs. The examination of this data provides an opportunity to develop an opinion on data prioritization and stage appropriateness of assays.
A Systematic Analysis of Physicochemical and ADME Properties of All Small Molecule Kinase Inhibitors Approved by US FDA from January 2001 to October 2015
Published 2017 in Current Medicinal Chemistry
ABSTRACT
PUBLICATION RECORD
- Publication year
2017
- Venue
Current Medicinal Chemistry
- Publication date
2017-08-31
- Fields of study
Medicine, Chemistry, Computer Science
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- adme properties
Absorption, distribution, metabolism, and excretion characteristics collected to describe pharmacokinetic behavior.
Aliases: absorption distribution metabolism excretion properties, ADME data
- advancement criteria
The rules or thresholds used to decide whether a compound should progress in a discovery program.
Aliases: progression criteria
- data prioritization
The process of deciding which data types are most useful or actionable at a given stage of discovery.
Aliases: information prioritization
- developability
The extent to which a compound is suitable for progression in drug discovery and development.
Aliases: drug developability
- physicochemical properties
Chemical descriptors such as size, polarity, and lipophilicity used to characterize the inhibitors.
Aliases: physicochemical data, chemical properties
- retrospective analysis
A backward-looking examination of previously approved drugs to identify patterns in their properties and development.
Aliases: backward-looking analysis
- stage appropriateness
The match between a type of assay or information and the discovery stage at which it is used.
Aliases: stage-appropriate data, assay stage appropriateness
- us fda-approved kinase inhibitors
Small-molecule kinase inhibitors approved by the US FDA within the January 2001 to October 2015 window considered in the analysis.
Aliases: approved kinase inhibitors, FDA-approved kinase inhibitors
REFERENCES
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