title: Anticancer properties of nimbolide and pharmacokinetic considerations to accelerate its development.
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.
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.|Department of Pharmacology, National University Health System, Singapore.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Wang
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.|Department of Pharmacy, National University of Singapore, Singapore.
authors.forename: Do Dang Khoa
authors.initials: DD
authors.lastname: Phan
authors.affiliation: Department of Pharmacology, National University Health System, Singapore.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore.
authors.forename: Pei-Shi
authors.initials: PS
authors.lastname: Ong
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.|Department of Pharmacy, National University of Singapore, Singapore.
authors.forename: Win Lwin
authors.initials: WL
authors.lastname: Thuya
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.|Department of Haematology-Oncology, National University Health System, Singapore.
authors.forename: Ross
authors.initials: R
authors.lastname: Soo
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.|Department of Haematology-Oncology, National University Health System, Singapore.
authors.forename: Andrea Li-Ann
authors.initials: AL
authors.lastname: Wong
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.|Department of Haematology-Oncology, National University Health System, Singapore.
authors.forename: Wei Peng
authors.initials: WP
authors.lastname: Yong
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.|Department of Haematology-Oncology, National University Health System, Singapore.
authors.forename: Soo Chin
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore.
authors.forename: Paul Chi-Lui
authors.initials: PC
authors.lastname: Ho
authors.affiliation: Department of Pharmacology, National University Health System, Singapore.
authors.forename: Gautam
authors.initials: G
authors.lastname: Sethi
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.|Department of Pharmacology, National University Health System, Singapore.|Department of Haematology-Oncology, National University Health System, Singapore.
authors.forename: Boon Cher
authors.initials: BC
authors.lastname: Goh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D031601:Azadirachta / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D036701:Limonins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D036701:Limonins; D010936:Plant Extracts; C042198:nimbolide
keywords: anticancer property; nimbolide; pharmacodynamics; pharmacokinetics; toxicology