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.

journal_name

Bioorg Med Chem Lett

authors

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

doi

10.1016/j.bmcl.2013.04.067

subject

Has Abstract

pub_date

2013-07-01 00:00:00

pages

3891-5

issue

13

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(13)00548-9

journal_volume

23

pub_type

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