IMR Press / FBL / Volume 26 / Issue 11 / DOI: 10.52586/5028
Open Access Review
Protein kinases as therapeutic targets to develop anticancer drugs with natural alkaloids
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1 Department of Pharmacology, School of Pharmacy, Southwest Medical University, 646000 Luzhou, Sichuan, China
2 Rizhao Hospital of Traditional Chinese Medicine, 276826 Rizhao, Shandong, China
3 Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
*Correspondence: (Xiukun Lin); (Shousong Cao)
Front. Biosci. (Landmark Ed) 2021, 26(11), 1349–1361;
Submitted: 30 May 2021 | Revised: 25 July 2021 | Accepted: 29 September 2021 | Published: 30 November 2021
Copyright: © 2021 The Author(s). Published by BRI.
This is an open access article under the CC BY 4.0 license (

Backgroud: Protein kinases play an important role in cell proliferation, differentiation, mobility and cell cycle arrest etc. These enzymes act as important targets in developing anticancer agents. Over the years, a large number of protein kinase inhibitors have been discovered and developed as anticancer agents for the treatment of cancers clinically. However, the drug-resiatance and off-targeting limit their effeciancy for the treatment of human cancer. Materials and methods: Alkaloids are an important class of natural products with broad spectrum biological activities. In the past decades, numerus alkaloids with significant anticancer activity by inhibiting protein kinases were identified. In the present mini-review, we will present the key enzymes including mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and janus-activated kinases/signal transducer and activator of transcription (JAK/STAT) targeted by alkaloids and highlight the special sites targeted by alkaloids on protein kinases and/or reversing drug resistance. Additionally, the challenge and prospect of developing alkaloids as new anticancer agents are also discussed. Conclusion: Alkaloids suppressed tumor growth through targeting different signaling pathways mediated by protein kinases of cancer cells. It is conceivable that novel alkaloids anticancer agents with promising clinical value will be developed in the future.

Protein kinase inhibitors
Anticancer activity
Fig. 1.
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