Near-infrared light controlled protein degradation by photo-caged lenalidomide and pomalidomide

Yaoji Zhu; Xiaosa Yan; Yinan Shi; Baohua Liu; Weiren Huang; Ling Chu

doi:10.1016/j.bioorg.2023.107050

Near-infrared light controlled protein degradation by photo-caged lenalidomide and pomalidomide

Bioorg Chem. 2024 Feb:143:107050. doi: 10.1016/j.bioorg.2023.107050. Epub 2023 Dec 21.

Authors

Yaoji Zhu¹, Xiaosa Yan², Yinan Shi¹, Baohua Liu³, Weiren Huang⁴, Ling Chu⁵

Affiliations

¹ School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.
² Department of Critical Care Medicine, Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen 518060, China.
³ Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen, China.
⁴ State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, China. Electronic address: pony8980@163.com.
⁵ School of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China. Electronic address: lingchu@mail.tsinghua.edu.cn.

PMID: 38163423
DOI: 10.1016/j.bioorg.2023.107050

Abstract

Immunomodulatory drugs (e.g. thalidomide, lenalidomide and pomalidomide) have been proven highly successful in clinical treatment of multiple myeloma. However, systematic degradation of zinc finger transcriptional factors induced by these drugs could lead to severe systematic toxicity in patients. Previous reports of NVOC caged pomalidomide attempted to regulate its activity using UVA irradiation, but their application was limited by high cytotoxicity and low tissue penetration. Here, we reported red-shifted BODIPY caged lenalidomide and pomalidomide that enabled red-light controlled protein degradation with spatiotemporal precision.

Keywords: Lenalidomide; NIR photodecaging; Pomalidomide; Protein degradation.

MeSH terms

Humans
Lenalidomide / pharmacology
Multiple Myeloma* / drug therapy
Proteolysis
Thalidomide* / pharmacology
Thalidomide* / therapeutic use

Substances

pomalidomide
Thalidomide
Lenalidomide