Related Experiment Video
Updated: Nov 2, 2025
Multi-photon Imaging of Tumor Cell Invasion in an Orthotopic Mouse Model of Oral Squamous Cell Carcinoma
Published on: July 25, 2011
Development of photocontrolled BRD4 PROTACs for tongue squamous cell carcinoma (TSCC)
Zhenzhen Li1, Siyue Ma1, Xingye Yang1
1Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (MOE), School of Pharmacy, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China.
Abstract:
The catalytic properties of small-molecule proteolysis targeting chimeras (PROTACs) may lead to uncontrolled degradation. Therefore, the main disadvantages of PROTACs are non-cancer specificity and relatively high toxicity, which limit the clinical application of PROTACs. The photocontrolled PROTACs (photoPROTACs) were proposed to overcome this issue, in which they can be triggered by ultraviolet A (UVA) or visible light to induce the degradation of the target protein. Herein, we designed several photoPROTACs to cause the degradation of bromodomain-containing protein 4 (BRD4) on-demand using 365 nm light. The representative compound N2 is proved to induce the degradation of BRD4 upon irradiation. Moreover, compound N2 was successfully applied in vivo to inhibit tumor growth in a zebrafish xenograft model of skin cancer tongue squamous cell carcinoma (TSCC) in a photocontrol manner.
Insights
Photocontrolled proteolysis targeting chimeras (photoPROTACs) offer precise control over protein degradation. This study developed photoPROTACs targeting BRD4, demonstrating effective on-demand degradation and tumor inhibition in vivo.
Area of Science:
- Medicinal Chemistry
- Molecular Biology
- Oncology
Background:
- Small-molecule proteolysis targeting chimeras (PROTACs) can cause uncontrolled protein degradation, limiting their clinical use due to toxicity and lack of specificity.
- Photocontrolled PROTACs (photoPROTACs) offer a solution by enabling light-inducible target protein degradation.
Purpose of the Study:
- To design and synthesize novel photoPROTACs for the on-demand degradation of bromodomain-containing protein 4 (BRD4).
- To evaluate the efficacy of these photoPROTACs in vitro and in vivo cancer models.
Main Methods:
- Design and synthesis of photoPROTAC compounds.
- In vitro assessment of BRD4 degradation upon light irradiation.
- In vivo evaluation of tumor growth inhibition in a zebrafish xenograft model of tongue squamous cell carcinoma (TSCC).
Main Results:
- Several photoPROTACs were synthesized, with compound N2 showing efficient BRD4 degradation upon 365 nm light irradiation.
- Compound N2 demonstrated successful photocontrolled inhibition of tumor growth in a zebrafish TSCC xenograft model.
- The developed photoPROTACs offer a precise and controllable method for targeting BRD4.
Conclusions:
- Photocontrolled PROTACs represent a promising strategy to overcome the limitations of traditional PROTACs.
- The developed BRD4-targeting photoPROTACs show potential for targeted cancer therapy with enhanced safety and specificity.
More Related Videos
07:17Development of an Innovative LED-based Illumination Device for In Vitro Application of Photodynamic Therapy with Rose Bengal
Published on: September 12, 2025
08:15Fabrication of Tongue Extracellular Matrix and Reconstitution of Tongue Squamous Cell Carcinoma In Vitro
Published on: June 20, 2018