ArticleCell cycle (Georgetown, Tex.)2020
A novel EZH2 inhibitor induces synthetic lethality and apoptosis in PBRM1-deficient cancer cells.
Article in Cell cycle (Georgetown, Tex.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Pbrm1 Loss Induces a Permissive Chromatin State for Cholangiocytic Differentiation and Cholangiocarcinoma Formation.Cellular and molecular gastroenterology and hepatology · 2026Article
- Prolonged survival in a patient with pbrm1 mutated metastatic cholangiocarcinoma receiving tazemetostat.NPJ precision oncology · 2025Article
- PRMT1 inhibition perturbs RNA metabolism and induces DNA damage in clear cell renal cell carcinoma.Nature communications · 2024Article
- PBRM1 presents a potential ctDNA marker to monitor response to neoadjuvant chemotherapy in cervical cancer.iScience · 2024Article
- The effects of ARID1A mutation in gastric cancer and its significance for treatment.Cancer cell international · 2023Review
- Mutual Regulation of ncRNAs and Chromatin Remodeling Complexes in Normal and Pathological Conditions.International journal of molecular sciences · 2023Review
- Advances in the role of SWI/SNF complexes in tumours.Journal of cellular and molecular medicine · 2023Review
- SWI/SNF complex gene variations are associated with a higher tumor mutational burden and a better response to immune checkpoint inhibitor treatment: a pan-cancer analysis of next-generation sequencing data corresponding to 4591 cases.Cancer cell international · 2022Article
- Article
- PBRM1 Deficiency Sensitizes Renal Cancer Cells to DNMT Inhibitor 5-Fluoro-2'-Deoxycytidine.Frontiers in oncology · 2022Article
- Exploring EZH2-Proteasome Dual-Targeting Drug Discovery through a Computational Strategy to Fight Multiple Myeloma.Molecules (Basel, Switzerland) · 2021Article
- Potential role for EZH2 in promotion of asthma through suppression of miR-34b transcription by inhibition of FOXO3.Laboratory investigation; a journal of technical methods and pathology · 2021Article
- Sophisticated Conversations between Chromatin and Chromatin Remodelers, and Dissonances in Cancer.International journal of molecular sciences · 2021Review
- Exploiting vulnerabilities of SWI/SNF chromatin remodelling complexes for cancer therapy.Oncogene · 2021Review
- Targeting EZH2-mediated methylation of histone 3 inhibits proliferation of pediatric acute monocytic leukemia cellsCancer biology & therapy · 2021Article
- A recent development of new therapeutic agents and novel drug targets for cancer treatment.SAGE open medicine · 2021Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inhibition of enhancer of zeste homolog 2 (EZH2) has been suggested to be synthetic lethal with polybromo-1 (PBRM1) deficiency, rendering EZH2 to be an attractive target for the treatment of PBRM1 frequently mutated cancers. In the current study, we combined computational and biochemical approaches to establish an efficient system for the screening and validation of synthetic lethal inhibitors from a large pool of chemical compounds. Five putative EZH2 inhibitors were identified through structure-based virtual screening from 47,737 chemical compounds and analyzed with molecular dynamics. The efficacy of these compounds against EZH2 was tested using PBRM1 deficient and wide-type cell lines. The compound L501-1669 selectively inhibited the proliferation of PBRM1-deficient cells and down-regulated the tri-methylation of histone H3 at Lysine 27 (H3K27me3). Importantly, we also observed an increase in apoptotic activities in L501-1669 treated PBRM1-deficient cells. Taken together, our results demonstrate that L501-1669 is a selective EZH2 inhibitor with promising application in the targeted therapy of PBRM1-deficient cancers.
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