Properties of FDA-approved small molecule protein kinase inhibitors: a 2025 update.

in Pharmacological research by Robert Roskoski

TLDR

  • The study provides an overview of the 85 FDA-approved small molecule protein kinase inhibitors, highlighting their molecular properties, therapeutic applications, and potential future directions.

Abstract

Because of the deregulation of protein kinase action in many inflammatory diseases and cancer, the protein kinase family has become one of the most significant drug targets in the 21century. There are 85 FDA-approved protein kinase antagonists that target about two dozen different enzymes and four of these drugs were approved in 2024 and a fifth was approved in 2025. Of these drugs, five target dual specificity protein kinases (MEK1/2), fourteen inhibit protein-serine/threonine protein kinases, twenty-one block nonreceptor protein-tyrosine kinases, and 45 target receptor protein-tyrosine kinases. The data indicate that 75 of these drugs are prescribed for the treatment of neoplasms. Seven drugs (abrocitinib, baricitinib, deucravacitinib, deuruxolitinib, ritlecitinib, tofacitinib, upadacitinib) are prescribed for the management of inflammatory diseases (atopic dermatitis, rheumatoid arthritis, psoriasis, alopecia areata, and ulcerative colitis). Of the 85 FDA-approved agents, about two dozen are used in the treatment of multiple diseases. The following four drugs received FDA approval in 2024 - deuruxolitinib (alopecia areata), ensartinib and lazertinib (non-small cell lung cancer), and tovorafenib (pediatric glioma) while mirdametinib was approved in 2025 for the treatment of type I neurofibromatosis (von Recklinghausen disease). Apart from netarsudil, temsirolimus, and trilaciclib, the approved protein kinase blockers are orally bioavailable. This article summarizes the physicochemical properties of all 85 FDA-approved small molecule protein kinase inhibitors including the molecular weight, number of hydrogen bond donors/acceptors, ligand efficiency, lipophilic efficiency, polar surface area, and solubility. A total of 39 of the 85 FDA-approved drugs have a least one Lipinski rule of 5 violation.

Overview

  • This study summarizes the 85 FDA-approved small molecule protein kinase inhibitors, focusing on their physicochemical properties,
  • The study examines the protein kinase family as a significant drug target in the 21st century, with four novel approvals in 2024 and one in 2025.
  • The main objective of the study is to provide a comprehensive overview of the FDA-approved protein kinase inhibitors, their molecular properties, and potential therapeutic applications.

Comparative Analysis & Findings

  • Of the 85 FDA-approved protein kinase antagonists, five target dual specificity protein kinases, 14 inhibit protein-serine/threonine protein kinases, 21 block nonreceptor protein-tyrosine kinases, and 45 target receptor protein-tyrosine kinases.
  • The majority of these drugs (75) are prescribed for the treatment of neoplasms, while seven are used for inflammatory diseases such as atopic dermatitis, rheumatoid arthritis, and psoriasis.
  • The study notes that about two dozen FDA-approved agents are used in the treatment of multiple diseases, highlighting the versatility of these inhibitors in modern medicine.

Implications and Future Directions

  • The findings of this study can facilitate the development of novel protein kinase inhibitors with improved efficacy and reduced side effects.
  • Future research can focus on exploring the mechanisms of action of these inhibitors, as well as their potential interactions with other therapeutic agents.
  • Additionally, this study suggests that there is a high demand for new protein kinase inhibitors, particularly those that can target multiple diseases or disease pathways, making it an attractive area for investment and innovation.
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