2. Academic Validation
  3. Identification of 2-Benzylidene-tetralone Derivatives as Highly Potent and Reversible Firefly Luciferase Inhibitors

Identification of 2-Benzylidene-tetralone Derivatives as Highly Potent and Reversible Firefly Luciferase Inhibitors

  • ACS Med Chem Lett. 2022 Jan 20;13(2):304-311. doi: 10.1021/acsmedchemlett.1c00671.
Yunzhi Li 1,  Chaoying Jin 1,  Huiying Xu 1,  Weijian Wu 1,  Youqiao Wang 1,  Jiaxin Wu 1,  Tingyu Liu 2,  Guohui Wan 1,  Xin Yue 3 4,  Xianzhang Bu 1
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
  • 2 State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
  • 3 Department of Radiation Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
  • 4 Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
PMID: 35178187 DOI: 10.1021/acsmedchemlett.1c00671
Abstract

The extensive applications of Firefly luciferase (Fluc) in numerous biological, biomedical, and clinical investigations rendered an urgent need for efficient and biocompatible Fluc inhibitors for the construction of novel assay platforms. Herein we describe the identification of 2-benzylidene-tetralone derivatives as highly potent and reversible Firefly luciferase inhibitors by competing with d-luciferin. The most active compound 48 was found to have >7000 fold higher potency (IC50 = 0.25 nM) than that of the well-known luciferase inhibitor resveratrol (IC50 = 1.9 μM) biochemically with sub- to low nanomolar IC50 values, and it can efficiently block the Fluc generated bioluminescence in vivo.

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