2. Academic Validation
  3. Design, synthesis and biological evaluation of novel HIF-1α PROTACs degrader as potent anti-cervical cancer agents

Design, synthesis and biological evaluation of novel HIF-1α PROTACs degrader as potent anti-cervical cancer agents

  • Bioorg Med Chem Lett. 2026 Feb 1:131:130443. doi: 10.1016/j.bmcl.2025.130443.
En-Jie Zhu 1,  Xing-Sheng Bu 2,  Ying Yue 3,  Yong-Sheng Hou 4,  Jia-Rong Liu 5,  Tharcisse Gatera 1,  Shu-Yang Ni 1,  Tian Chai 4,  Xing-Rong Wang 6,  Jun-Li Yang 7
Affiliations

Affiliations

  • 1 CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Lanzhou 730000, People's Republic of China; University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
  • 2 College of Pharmacy, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, People's Republic of China.
  • 3 College of Life Science, Northwest Normal University, Lanzhou 730070, People's Republic of China.
  • 4 CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Lanzhou 730000, People's Republic of China.
  • 5 Department of General Surgery, Affiliated Hospital of Northwest Minzu University, Lanzhou 730030, People's Republic of China.
  • 6 CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Lanzhou 730000, People's Republic of China. Electronic address: wangxr@licp.cas.cn.
  • 7 CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Lanzhou 730000, People's Republic of China. Electronic address: yangjl@licp.cas.cn.
PMID: 41130325 DOI: 10.1016/j.bmcl.2025.130443
Abstract

Cervical Cancer is the fourth most common and deadly Cancer globally. Hypoxia-inducible factor-1α (HIF-1α) plays a key promoter of tumor progression and treatment resistance, making it an important Anticancer target. Here, we designed and synthesized a series of novel HIF-1α-targeting PROTAC degraders based on LW-6 and its derivative W-1. Among them, Z12 showed the strongest anti-proliferative and HIF1α degradation activities in HeLa cells. Z12 promoted HIF-1α degradation via the ubiquitin-proteasome pathway by facilitating the formation of a HIF-1α/VHL ternary complex. Furthermore, Z12 inhibited HeLa cell proliferation, migration, and colony formation, induced Apoptosis, and reduced p-MEK and p-AKT expression in the MAPK and PI3K/Akt pathways. This work offers a promising strategy for developing HIF1α-PROTAC degraders and treating cervical Cancer.

Keywords

Anti-cervical cancer; HIF-1α; HIF-1α degradation mechanism; LW-6; PROTAC degrader.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z