Latest @ CSI

Anticancer Properties of Nimbolide and Pharmacokinetic Considerations to Accelerate its Development. (Oncotarget, Mar 2016)

Wang L1,2, Phan DD1,3, Zhang J2, Ong PS3, Thuya WL1,3, Soo RA1,4, Wong AL1,4, Yong WP1,4, Lee SC1,4, Ho PC3, Sethi G2, Goh BC1,2,4

1Cancer Science Institute of Singapore, National University of Singapore, Singapore.
2Department of Pharmacology, National University Health System, Singapore.
3Department of Pharmacy, National University of Singapore, Singapore.
4Department of Haematology-Oncology, National University Health System, Singapore.

Abstract:

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.