2. Academic Validation
  3. Integrating virtual screening and molecular dynamics simulations to identify emodin as a PYCR1 inhibitor modulating docetaxel sensitivity in prostate cancer

Integrating virtual screening and molecular dynamics simulations to identify emodin as a PYCR1 inhibitor modulating docetaxel sensitivity in prostate cancer

  • J Enzyme Inhib Med Chem. 2026 Dec;41(1):2622725. doi: 10.1080/14756366.2026.2622725.
Shuai Liu 1,  Yongfeng Lao 1,  Long Cheng 1,  Xi Xiao 1,  Longtu Ma 1,  Wenyun Wang 2,  Kun Zhao 1,  Wenxuan Li 1,  Zhongze Zhou 1,  Qingchao Li 2,  Yan Tao 3,  Shanhui Liu 3,  Zhilong Dong 2
Affiliations

Affiliations

  • 1 Department of Urology, The Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China.
  • 2 Department of Urology, Gansu Province Clinical Research Center for Urinary System Disease, The Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China.
  • 3 Institute of Urology, Gansu Province Clinical Research Center for Urinary System Disease, The Second Hospital and Clinical Medical School, Lanzhou University, Lanzhou, Gansu, China.
PMID: 41665114 DOI: 10.1080/14756366.2026.2622725
Abstract

Docetaxel (DTX) resistance is the main cause of treatment failure in castration-resistant prostate Cancer (CRPC). Pyrroline-5-carboxylic acid reductase 1 (PYCR1) is an enzyme involved in proline metabolism. It is highly expressed in various cancers and promotes malignant progression, yet its role in DTX resistance in prostate Cancer remains unclear. In this study, bioinformatics analyses and in vitro/vivo experiments demonstrated that interfering with PYCR1 expression modulates the sensitivity of prostate Cancer cells to DTX. Subsequently, via structure-based virtual screening, molecular dynamics simulations, and cellular thermal shift assay (CETSA), emodin-an anthraquinone compound-was identified as a PYCR1-targeting agent. Collectively, these findings suggest that PYCR1 may serve as a key target mediating DTX resistance in prostate Cancer, and the emodin-DTX combination provides a promising potential clinical strategy to overcome such resistance. Finally, its functions and safety were also verified through in vitro experiments.

Keywords

Docetaxel; PYCR1; emodin; prostate cancer; virtual screening.

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