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
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.