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Kinases and their derived inhibitors from natural products

Takudzwa Chipeperengo Chiwoneso1, Yajing Luo1, Yifan Xu1

  • 1State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198 China.

Bioorganic Chemistry
|February 5, 2025
PubMed

Insights

Protein kinase inhibitors (PKIs) are crucial in cancer treatment but face challenges like toxicity and drug resistance. This review analyzes natural product-derived PKIs to guide the development of safer, more effective cancer therapies.

Area of Science:

  • Oncology
  • Biochemistry
  • Medicinal Chemistry

Background:

  • Protein kinase dysregulation is a key feature in many cancers, with mechanisms still under investigation.
  • Early protein kinase inhibitors (PKIs) from natural products had high cytotoxicity, while synthetic ones face drug resistance.
  • Understanding kinase function is vital for developing targeted cancer therapies.

Purpose of the Study:

  • To review the progress in understanding protein kinases' role in cancer.
  • To analyze FDA-approved and failed natural product-derived kinase inhibitors (NPDKIs).
  • To advance medicinal chemistry strategies for developing safer and more effective PKIs.

Main Methods:

  • Literature review of protein kinase function and dysregulation in cancer.
  • Analysis of synthesis and modification of FDA-approved NPDKIs.
  • Examination of NPDKIs that failed clinical trials.

Main Results:

  • Identified challenges in current PKI development, including toxicity and drug resistance.
  • Highlighted successful and unsuccessful strategies in NPDKI development.
  • Provided insights into the chemical modifications influencing PKI efficacy and safety.

Conclusions:

  • Further research into NPDKIs can lead to improved cancer treatment outcomes.
  • Medicinal chemistry approaches should focus on enhancing efficacy while minimizing toxicity.
  • Understanding historical NPDKI successes and failures is key to future drug design.
Keywords:
Natural product derived kinase inhibitors (NPDKI)Protein kinase (PK)Protein kinase inhibitor (PKI)

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