2. Academic Validation
  3. A novel 2-iminobenzimidazole compound, XYA1353, displays in vitro and in vivo anti-myeloma activity via targeting NF-κB signaling

A novel 2-iminobenzimidazole compound, XYA1353, displays in vitro and in vivo anti-myeloma activity via targeting NF-κB signaling

  • Mol Cell Biochem. 2023 May 19. doi: 10.1007/s11010-023-04764-6.
Jian Gao # 1,  Jian Zhou # 2,  Menghui Zhang 2,  Yan Zhang 2,  Yindi Zeng 2,  Shihao Li 3,  Kailin Xu 4 5,  Ruosi Yao 6 7 8
Affiliations

Affiliations

  • 1 School of Medicine, Anhui University of Science and Technology, Huainan, China.
  • 2 Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 3 Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu, China.
  • 4 Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. lihmd@163.com.
  • 5 Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. lihmd@163.com.
  • 6 Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. yaors908@163.com.
  • 7 Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China. yaors908@163.com.
  • 8 Xuzhou Ruihu Health Management and Consulting Co., Ltd, Xuzhou, Jiangsu, China. yaors908@163.com.
  • # Contributed equally.
PMID: 37204666 DOI: 10.1007/s11010-023-04764-6
Abstract

Multiple myeloma (MM) is an accumulated disease of malignant plasma cells, which is still incurably owing to therapeutic resistance and disease relapse. Herein, we synthesized a novel 2-iminobenzimidazole compound, XYA1353, showing a potent anti-myeloma activity both in vitro and in vivo. Compound XYA1353 dose-dependently promoted MM cell Apoptosis via activating caspase-dependent endogenous pathways. Moreover, compound XYA1353 could enhance bortezomib (BTZ)-mediated DNA damage via elevating γH2AX expression levels. Notably, compound XYA1353 interacted synergistically with BTZ and overcame drug resistance. RNA Sequencing analysis and experiments confirmed that compound XYA1353 inhibited primary tumor growth and myeloma distal infiltration by disturbing canonical NF-κB signaling pathway via decreasing expression of P65/P50 and p-IκBα phosphorylation level. Due to its importance in regulating MM progression, compound XYA1353 alone or combined with BTZ may potentially exert therapeutic effects on multiple myeloma by suppressing canonical NF-κB signaling.

Keywords

Apoptosis; Drug resistance; Multiple myeloma; NF-κB pathway; XYA1353.

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