Abstract
Metabolism-mediated drug adverse effects (e.g., drug-drug interaction, bioactivation, etc.) strongly limit the utilization of clinical drugs. The present study aims to predict the metabolic capability of cytochrome P450 (CYP) 3A4 toward pazopanib which is an excellent drug exhibiting therapeutic role toward various cancers especially for ovarian cancer. Pazopanib can be well docked into the activity cavity of CYP3A4, and the interaction structure in pazopanib was methyl group located besides nitrogen in the five-membered ring. The distance between the hydrogen atom in methyl group and active center is 3.64 Å. The interaction amino acid is Glu374. Furthermore, both pazopanib and ketoconazole were docked into the activity cavity of CYP3A4 to compare their binding potential. The distance between ketoconazole and activity center (2.10 Å) is closer than the distance between pazopanib and activity center of CYP3A4, indicating the easy influence of CYP3A4 inhibitor toward the metabolism of pazopanib. All these data were helpful for the clinical application of pazopanib, and R&D of other tinib drug candidates as new anti-tumor drugs.
References
Oct 7, 2009·Chemical Research in Toxicology·Xiaohai LiMichael D Cameron
Nov 26, 2009·Chemistry & Biodiversity·Amit S Kalgutkar, Mary T Didiuk
Mar 18, 2010·British Journal of Clinical Pharmacology·Zhong-Ze FangLing Yang
Apr 8, 2010·Molecular Cancer Therapeutics·Kae HashimotoRobert S Kerbel
Apr 13, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Xiaohai LiMichael D Cameron
Jun 30, 2010·Gynecologic Oncology·Michael FriedlanderJoanne J Lager
May 26, 2011·Expert Opinion on Drug Metabolism & Toxicology·Zhong-Ze FangLing Yang
May 3, 2013·Cancer Chemotherapy and Pharmacology·Antoinette R TanJoseph J Stephenson
Jul 23, 2013·Journal of Gynecologic Oncology·Emma L BarberNikki L Neubauer
Nov 1, 2013·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Stacey M SteinFranco Muggia
Jan 28, 2014·Biochemical Pharmacology·Rui GuMichael Murray
Feb 19, 2014·Pharmacogenomics·Andrey V KhruninSvetlana A Limborska
Feb 27, 2014·Clinical Pharmacology and Therapeutics·J E SagerN Isoherranen
Mar 19, 2014·Toxicology and Applied Pharmacology·Hai-Ying MaZhong-Ze Fang
Apr 11, 2014·Integrative Biology : Quantitative Biosciences From Nano to Macro·Shivani SharmaOliver Dorigo
Apr 22, 2014·Molecular and Cellular Endocrinology·Marta LlauradóMarina Rigau
Apr 24, 2014·European Journal of Drug Metabolism and Pharmacokinetics·Tao LiuYanguo Zhang
Apr 25, 2014·Journal of Gynecologic Oncology·Ho-Suap HahnTae-Jin Kim
Citations
Feb 15, 2018·The Journal of Pharmacology and Experimental Therapeutics·Jamie E MoscovitzYan Weng
Jan 22, 2020·Biomolecular Concepts·Kelath Murali Manoj
Dec 8, 2016·Oncotarget·Lingling ZhangYingjie Zhang
Apr 18, 2019·Medical Oncology·Anne-Laure ClairetSamuel Limat
Aug 14, 2018·Journal of Medicinal Chemistry·Marie-Noëlle PaludettoAnne Robert