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Basic Information

ID: ALA2396643

Journal: Bioorg Med Chem Lett

Title: Discovery of a small molecular compound simultaneously targeting RXR and HADC: design, synthesis, molecular docking and bioassay.

Authors: Chen GL, Wang LH, Wang J, Chen K, Zhao M, Sun ZZ, Wang S, Zheng HL, Yang JY, Wu CF.

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.

CiteXplore: 23707260

DOI: 10.1016/j.bmcl.2013.04.067