2. Academic Validation
  3. Identification of novel HIF2α inhibitors: a structure-based virtual screening approach

Identification of novel HIF2α inhibitors: a structure-based virtual screening approach

  • J Enzyme Inhib Med Chem. 2026 Dec;41(1):2606435. doi: 10.1080/14756366.2025.2606435.
Shasha Zhou 1,  Shengnan Yin 2,  Shudan Yang 3,  Yuting Wang 3,  Panfeng Feng 1
Affiliations

Affiliations

  • 1 Department of Pharmacy, Affiliated Hospital 2 of Nantong University, Nantong First People's Hospital, Nantong, China.
  • 2 Department of Pharmacy, Taizhou Affiliated Hospital of Nanjing University of Chinese Medicine, Taizhou, China.
  • 3 Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, China.
PMID: 41493169 DOI: 10.1080/14756366.2025.2606435
Abstract

HIF2α is aberrantly upregulated in some renal cell carcinomas due to VHL mutations, supporting HIF2α inhibition as a compelling therapeutic approach for such cases. Therefore, the six compounds (designated as Compounds 1-6) were screened from the Maybridge database based on the constructed pharmacophore model and molecular docking. Subsequently, the docking models of Compounds 1-6 with HIF2α were analysed. Affinity assays revealed that both Compound-4 and Compound-5 exhibited robust affinity towards human recombinant HIF2α. MD simulations displayed that Compound-4 and Compound-5 stably bound to the active pocket of HIF2α. Cell experiments demonstrated that Compound-4 effectively inhibited the growth of the 786-O human renal cell carcinomas line (IC50 = 1.35 ± 0.06 μM). This study demonstrates that Compound-4 may serve as a potential candidate compound for renal cell carcinomas therapy.

Keywords

HIF2α; inhibitor; pharmacophore screening; renal cell carcinomas.

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