https://doi.org/10.1016/j.apsb.2025.10.031
This new article publication from Acta Pharmaceutica Sinica B , discusses DHL-11, a novel prieurianin-type limonoid isolated from Munronia henryi , targeting IMPDH2 to inhibit triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by the poorest prognosis, and poses a significant threat to women's health. In this study two novel prieurianin-type limonoids extracted from Munronia henryi were identified, one of which, named DHL-11, exhibited antitumor activity against TNBC cells. DHL-11 suppressed cell proliferation and migration, induced G2/M cell cycle arrest and apoptosis, and effectively increased the accumulation of reactive oxygen species (ROS) and cellular DNA damage in TNBC cells. Mechanistically, it was found that DHL-11 binds to the non-catalytic pocket of IMPDH2 and disrupts the interaction between IMPDH2 and FANCI, leading to the degradation of the IMPDH2 protein. The decrease of IMPDH2 protein reduced guanine synthesis, increased ROS levels, and induced DNA damage. DHL-11 significantly inhibited the growth of breast cancer patient-derived organoids with high IMPDH2 expression. Furthermore, DHL-11 inhibited the growth and metastasis of TNBC xenografts in vivo with favorable biosafety profiles. These findings highlight the potential of DHL-11 as a novel IMPDH2 degrader for the treatment of IMPDH2-positive TNBC.
Keywords: Limonoids, DHL-11, TNBC, ROS, DNA damage, IMPDH2, Guanine, FANCI
Graphical Abstract: available at https://ars.els-cdn.com/content/image/1-s2.0-S2211383525007099-ga1_lrg.jpg
DHL-11 competes with FANCI to bind IMPDH2, destabilizing it, reducing GMP synthesis, causing DNA damage and replication stress, and inducing TNBC cell apoptosis.
# # # # # #
The Journal of the Institute of Materia Medica, the Chinese Academy of Medical Sciences and the Chinese Pharmaceutical Association .
For more information please visit https://www.journals.elsevier.com/acta-pharmaceutica-sinica-b/
Editorial Board: https://www.journals.elsevier.com/acta-pharmaceutica-sinica-b/editorial-board
APSB is available on ScienceDirect ( https://www.sciencedirect.com/journal/acta-pharmaceutica-sinica-b ).
Submissions to APSB may be made using Editorial Manager ® ( https://www.editorialmanager.com/apsb/default.aspx ).
CiteScore: 24.3
Impact Factor: 14.6 (Top 6 journal in the category of Pharmacology and pharmacy)
JIF without self-citation: 13.8
ISSN 2211-3835
# # # # #
Yu Zhu, Zhibi Zhang, Xueqin Dai, Wenjing Liu, Jian Sun, Jialing Liu, Yuxin Zhao, Wenlong Ren, Chenglong Pan, Zhongmei Zhou, Ying Yan, Longlong Zhang, Ceshi Chen, DHL-11, a novel prieurianin-type limonoid isolated from Munronia henryi, targeting IMPDH2 to inhibit triple-negative breast cancer, Acta Pharmaceutica Sinica B, Volume 16, Issue 1, 2026, Pages 287-304, ISSN 2211-3835, https://doi.org/10.1016/j.apsb.2025.10.031