title: Design, synthesis and biological evaluation of deuterated nintedanib for improving pharmacokinetic properties.
abstract: Nintedanib is a novel triple angiokinase inhibitor that inhibits three growth factors simultaneously. Deuterated derivatives of nintedanib at certain metabolically active sites were prepared and evaluated in vitro and in vivo. In particular, deuterated compound SKLB-C2202 had significantly improved pharmacokinetic properties compared with nintedanib. These efforts lay the foundation for further investigating the druggability of SKLB-C2202.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
authors.forename: Ruixue
authors.initials: R
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhan
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Peng
authors.affiliation: Hinova Pharmaceuticals Inc, Suite 801, Building C1, #88 South KeYuan Road, Chengdu Tianfu Life Science Park, Chengdu, 610041, China.
authors.forename: Xuehai
authors.initials: X
authors.lastname: Pang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.|Hinova Pharmaceuticals Inc, Suite 801, Building C1, #88 South KeYuan Road, Chengdu Tianfu Life Science Park, Chengdu, 610041, China.
authors.forename: Yuanwei
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D003903:Deuterium / Q000737:chemistry*; D007211:Indoles / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D007553:Isotope Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D003903:Deuterium; C530716:nintedanib
keywords: Nintedanib; antitumor activity; deuterium isotope effect; triple angiokinase inhibitor