Related Experiment Video
Updated: Apr 24, 2026
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
[Application of temperature sensitive yeast models with definite target in the screening of potential human Pin1
Abstract:
This study is to explore new lead compounds by inhibition of Pin1 for anticancer therapy using temperature sensitive mutants. As Pin1 is conserved from yeast to human, we established a high-throughput screening method for Pin1 inhibitors, which employed yeast assay. This method led to the identification of one potent hits, 8-11. In vitro, 8-11 inhibited purified Pin1 enzyme activity with IC50 of (10.40 +/- 1.68) micromol x L(-1), induced G1 phase arrest and apoptosis, showed inhibitory effects on a series of cancer cell proliferation, reduced Cyclin D1 expression, was defined as reciprocally matched for protein-ligand complex in virtual docking analysis and reduced cell migration ability. In vivo, we could observe reduction of tumor volume after treatment with 8-11 in xenograft mice compared with vehicle DMSO treatment. Altogether, these results provide for the first time the involvement of 8-11 in the anticancer activity against Pin1.
Insights
Researchers identified a novel compound, 8-11, that inhibits Pin1 (Peptidyl-prolyl cis-trans isomerase) enzyme activity. This compound shows significant anticancer effects in vitro and in vivo, offering a new therapeutic strategy.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Pin1 (Peptidyl-prolyl cis-trans isomerase) is a crucial enzyme implicated in various cellular processes and cancer development.
- Targeting Pin1 presents a promising strategy for anticancer therapy.
- Developing effective Pin1 inhibitors is essential for advancing cancer treatment.
Purpose of the Study:
- To explore novel lead compounds that inhibit Pin1 activity for anticancer applications.
- To establish a high-throughput screening method for identifying Pin1 inhibitors.
- To evaluate the anticancer potential of a newly identified compound, 8-11.
Main Methods:
- Utilized a yeast-based high-throughput screening assay to identify Pin1 inhibitors.
- Conducted in vitro enzyme inhibition assays to determine the IC50 of compound 8-11.
- Performed cell-based assays to assess effects on cell cycle, apoptosis, proliferation, and migration.
- Employed virtual docking analysis to evaluate protein-ligand interactions.
- Evaluated in vivo efficacy using a xenograft mouse model.
Main Results:
- Identified compound 8-11 as a potent inhibitor of purified Pin1 enzyme activity (IC50 = 10.40 ± 1.68 µmol/L).
- Compound 8-11 induced G1 phase arrest and apoptosis in cancer cells.
- Demonstrated inhibitory effects on cancer cell proliferation and migration, and reduced Cyclin D1 expression.
- Virtual docking confirmed a reciprocal match for the protein-ligand complex.
- Observed significant tumor volume reduction in xenograft mice treated with 8-11.
Conclusions:
- Compound 8-11 exhibits significant anticancer activity through Pin1 inhibition.
- 8-11 demonstrates potential as a novel therapeutic agent for cancer treatment.
- This study provides the first evidence of 8-11's anticancer effects mediated by Pin1 inhibition.
