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Updated: Sep 10, 2025

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ALK5 kinase inhibitors in drug discovery: Structural insights and therapeutic applications

Fang-Yan Guo1, Siqi Li1, Changhao Zhang1

  • 1Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, 133002, China.

European Journal of Medicinal Chemistry
|August 27, 2025
PubMed

Insights

Activin receptor-like kinase-5 (ALK5) inhibitors show promise for treating cancer and fibrosis by targeting the TGF-β pathway. Research highlights clinical candidates, compounds, and challenges like cardiotoxicity for optimized therapies.

Area of Science:

  • Biochemistry and Molecular Biology
  • Pharmacology and Drug Discovery
  • Oncology

Background:

  • Transforming growth factor-β (TGF-β) signaling is crucial in cancer, inflammation, and fibrosis.
  • Activin receptor-like kinase-5 (ALK5) is a key mediator in the TGF-β pathway.
  • Targeting ALK5 with inhibitors offers a therapeutic strategy for various diseases.

Purpose of the Study:

  • To review recent advancements in ALK5 inhibitor research.
  • To focus on clinical candidates, synthetic, and natural compounds.
  • To discuss structure-activity relationships (SARs) and pharmacological profiles.

Main Methods:

  • Systematic review of current literature on ALK5 inhibitors.
  • Analysis of clinical trial data and preclinical studies.
  • Evaluation of pharmacokinetic (PK) and pharmacodynamic (PD) properties.

Main Results:

  • Identified promising ALK5 inhibitors with antitumor and antifibrotic potential.
  • Summarized SARs for various ALK5 inhibitor classes.
  • Discussed PK/PD profiles influencing drug efficacy and safety.

Conclusions:

  • ALK5 inhibitors represent a viable therapeutic avenue for cancer and fibrotic diseases.
  • Understanding SARs and PK/PD is essential for rational drug design.
  • Addressing challenges like cardiotoxicity is critical for successful clinical translation.
Keywords:
ALK5CancerKinaseSynthesisTGF-β

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