title: Discovery of a small molecular compound simultaneously targeting RXR and HADC: design, synthesis, molecular docking and bioassay.
abstract: Retinoid X receptor (RXR) and Histone deacetylase (HDAC) are considered important targets for anti-cancer therapy due to their crucial roles in genetic or epigenetic regulations of cancer development and progression. Here, we have designed and synthesized a novel compound which targets both RXR and HADC. This dual-targeting agent is derived from bexarotene and suberoylanilide hydroxamic acid (SAHA), prototypical RXR agonist and HDAC inhibitor, respectively. Molecular docking studies demonstrate that this agent has a relatively strong affinity to RXR and HADC. Importantly, it presents the potentials of activation of RXR and inhibition of HDAC in both cell-free and whole-cell assays, and displays anti-proliferative effect on representative cancer cell lines and drug-resistant cancer cell lines.
authors.affiliation: Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, PR China.
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Chen
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.forename: Man
authors.initials: M
authors.lastname: Zhao
authors.forename: Zhao-Zhu
authors.initials: ZZ
authors.lastname: Sun
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Zheng
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Yang
authors.forename: Chun-Fu
authors.initials: CF
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D047488:Retinoid X Receptors / Q000819:agonists*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047488:Retinoid X Receptors; D054852:Small Molecule Libraries; D006655:Histone Deacetylases