期刊
ONCOTARGET
卷 7, 期 28, 页码 44790-44802出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.8316
关键词
nimbolide; anticancer property; pharmacodynamics; pharmacokinetics; toxicology
资金
- National Research Foundation Singapore
- Singapore Ministry of Education under Its Research Centres of Excellence Initiative, and Clinician Scientist Award of NMRC
- Clinician Scientist Award of NMRC for Translational Pipeline: Developing novel therapeutics
Nimbolide is one of the main components in the leaf extract of Azadirachta indica (A. indica). Accumulating evidence from various in vitro and in vivo studies indicates that nimbolide possesses potent anticancer activity against several types of cancer and also shows potential chemopreventive activity in animal models. The main mechanisms of action of nimbolide include anti-proliferation, induction of apoptosis, inhibition of metastasis and angiogenesis, and modulation of carcinogen-metabolizing enzymes. Although multiple pharmacodynamic (PD) studies have been carried out, nimbolide is still at the infant stage in the drug development pipeline due to the lack of systematic pharmacokinetic (PK) studies and long-term toxicological studies. Preclinical PK and toxicological studies are vital in determining the dosage range to support the safety of nimbolide for first-in-human clinical trials. In this review, we will provide a comprehensive summary for the current status of nimbolide as an anticancer and chemopreventive lead compound, and highlight the importance of systematic preclinical PK and toxicological studies in accelerating the process of application of nimbolide as a therapeutic agent against various malignancies.
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