Ask about this productRelated genes to: EZH2 Blocking Peptide
- Gene:
- EZH2 NIH gene
- Name:
- enhancer of zeste 2 polycomb repressive complex 2 subunit
- Previous symbol:
- -
- Synonyms:
- EZH1, ENX-1, KMT6, KMT6A
- Chromosome:
- 7q36.1
- Locus Type:
- gene with protein product
- Date approved:
- 1995-12-21
- Date modifiied:
- 2019-04-23
Related products to: EZH2 Blocking Peptide
Related articles to: EZH2 Blocking Peptide
- Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is a multifunctional RNA-binding protein of the hnRNP family, yet its role in long non-coding RNA (lncRNA)-mediated epigenetic regulation during myogenesis remains unclear. The lncRNA Ppp1r1b-lncRNA is an established regulator of myogenesis that functions through interaction with Polycomb repressive complex 2 (PRC2) at myogenic gene promoters. Here, we investigated the role of hnRNPA1 in Ppp1r1b-lncRNA-mediated regulation of myogenesis. Fluorescence in situ hybridization (FISH) revealed the subcellular localization of Ppp1r1b-lncRNA, and RNA pulldown coupled with mass spectrometry identified associated proteins. Both hnRNPA1 and EZH2 were found to bind Ppp1r1b-lncRNA, but at distinct regions. Knockdown of hnRNPA1 in mouse C2C12 myoblasts reduced the interaction between Ppp1r1b-lncRNA and EZH2, as determined by RNA immunoprecipitation (RIP), decreased promoter occupancy of Ppp1r1b-lncRNA, as assessed by chromatin isolation by RNA purification (CHIRP), and reduced H3K27me3 levels at the MyoD1 and Myogenin promoters, as shown by chromatin immunoprecipitation (ChIP). These changes led to increased expression of muscle-specific transcription factors and sarcomeric genes, thereby disrupting the undifferentiated state. Furthermore, hnRNPA1 knockdown disrupted the interaction between the human ortholog PPP1R1B-lncRNA and PRC2 in human skeletal muscle precursor cells (hSMPCs). Together, these findings demonstrate that hnRNPA1 maintains the integrity of the Ppp1r1b-lncRNA-PRC2 complex and ensures proper epigenetic regulation of myogenic gene expression. This conserved hnRNPA1-Ppp1r1b-lncRNA-PRC2 regulatory axis represents a potential therapeutic target for muscle regeneration. - Source: PubMed
Kang XuedongZhao YanNelson Stanley FPyle AprilLusis Aldons JTouma Marlin - This study aims to investigate the role of FTO-mediated m6A modification in the promotion of angiogenesis by electroacupuncture (EA) after ischemic stroke via the miR-214/EZH2/eNOS signaling axis. - Source: PubMed
Publication date: 2026/05/12
Song ShizhenJu XinyaoZhang TingtingPeng WeiXie XueyunZhang WenqiZhou Shuang - Growing evidence has revealed that DEAD-box RNA helicase 5 (DDX5, also known as p68) and ubiquitin-conjugating enzyme E2T (UbE2T) are two emerging and highly promising cancer therapeutic targets. This article provides the first comprehensive review of the physical and functional relationship between these two cancer targets, further refining their therapeutic potentials in solid cancers. In addition, the consequences of simultaneously degrading DDX5 and UbE2T proteins by the small-molecule dual molecular glue degrader FL118 in difficult-to-treat advanced cancers are presented.Specifically, this article reviews: (1) the roles of DDX5 and UbE2T in diverse cancer DNA repair pathways; (2) the physical binding relationship and potential functional roles of DDX5 in topoisomerase regulation; (3) the involvement of DDX5 in EZH2- and NANOG-associated prostate cancer stem cell (PCSC)-driven neuroendocrine prostate cancer (NEPC), castration-resistant prostate cancer (CRPC), and metastatic CRPC (mCRPC); (4) the contributions of DDX5 and UbE2T to inflammatory and immune regulation within the tumor microenvironment (TME); (5) FL118 as a small-molecule dual molecular glue degrader selectively targeting both DDX5 and UbE2T; (6) the high efficacy of FL118 against multiple difficult-to-treat advanced and metastatic cancers, including advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), osteosarcoma, Ewing sarcoma, ovarian cancer, and glioma/glioblastoma; (7) the resistance of ABCG2-expressing cancer cells to common anticancer agents but not to FL118; (8) the favorable pharmacokinetic and toxicology profiles of FL118 in mice, rats, and dogs; (9) the distinct functions of DDX5 in normal tissues, cells, and organs versus cancer; and (10) FL118 as a drug platform enabling the development of novel analogs and derivatives.Based on this review, we conclude that DDX5 and UbE2T represent superior anticancer therapeutic targets, and that the high efficacy of FL118 against multiple difficult-to-treat cancers is attributable to its function as a bona fide small-molecule dual molecular glue degrader that physically targets and degrades both DDX5 and UbE2T. Strikingly, this activity is observed regardless of the expression status of ABC transporter proteins, ABCG2/BCRP, ABCB1/Pgp/MDR1, and/or ABCC1/MRP1 in cancer cells. - Source: PubMed
Publication date: 2026/05/18
Li FengzhiLing XiangChakraborty SayanTang Dean GMcLean KarenWu WenjieSule NorbertVadehra DeepakFountzilas ChristosGupta AjayTwist ClareOhm JoyceChatta GurkamalAbrams Scott I - Small cell lung cancer (SCLC) remains one of the most aggressive malignancies, characterized by rapid proliferation, early metastatic dissemination, and poor long-term survival despite initial sensitivity to therapy. SCLC shares several biologic and therapeutic principles with hematologic malignancies, including lineage state dependence, adaptive resistance through non-genetic plasticity, and emerging susceptibility to antigen-directed immune therapies. Reframing SCLC through this lens provides a conceptual framework for understanding treatment failure and identifying new therapeutic strategies. A defining feature of SCLC is its dynamic transition between neuroendocrine (NE) and non-neuroendocrine (non-NE) states, driven by epigenetic and transcriptional reprogramming rather than new genetic alterations. These state transitions regulate antigen expression, immune visibility, and therapeutic vulnerability, enabling tumors to evade both cytotoxic and immune-based treatments. This plasticity parallels lineage switching and antigen escape observed in hematologic malignancies treated with targeted and immune therapies. Recent advances in antigen-directed therapy, particularly bispecific T cell engagers and antibody-drug conjugates targeting lineage-associated proteins such as DLL3, SEZ6, and TROP2, have demonstrated promising clinical activity. However, therapeutic efficacy is limited by antigen heterogeneity, evolving tumor states, and microenvironmental barriers including immune exclusion and T cell dysfunction. Epigenetic therapies targeting regulators such as EZH2 and LSD1 offer a strategy to reprogram tumor state, enhance antigen presentation, and sensitize tumors to immunotherapy. Beyond lineage biology, SCLC exhibits dependence on replication stress and DNA damage response pathways, though targeting these vulnerabilities alone has yielded modest clinical benefit. Emerging evidence highlights the role of metabolic and stress-response adaptations, including lactate-mediated immune suppression and integrated stress signaling, in sustaining tumor fitness and resistance. Circulating tumor DNA and epigenomic profiling provide noninvasive approaches to monitor tumor evolution, lineage state, and treatment response over time, offering potential for biomarker-guided therapeutic adaptation. Overall, durable clinical benefit in SCLC will likely require temporally sequenced, biomarker driven combination strategies that anticipate and constrain tumor plasticity. Integrating lineage-directed targeting, epigenetic modulation, immune engagement, and metabolic intervention may enable more effective and sustained disease control in this highly adaptive cancer. - Source: PubMed
Publication date: 2026/04/30
Parmar KanakSurolia IraThomas Anish - Targeting membrane receptors underlies the success of antibody-drug conjugates (ADCs), yet single-receptor formats can be limited by heterogeneous expression, compensatory signaling, and variable internalization. Here we developed Multivalent Interchangeable Nanobody Degradation System (MINDS), a modular nanobody-Fc chassis that co-engages multiple membrane receptors, promotes their lysosomal co-depletion, and enables delivery of diverse intracellular payloads. As a proof of concept, we generated Tritazumab, a trispecific nanobody-Fc targeting three oncogenic receptors EGFR, cMET, and TfR1. Tritazumab incorporates a high-affinity, non-transferrin-competing anti-TfR1 nanobody that drives efficient uptake and lysosomal trafficking, enabling coordinated depletion of all three receptors. Across non-small cell lung cancer models, Tritazumab achieved rapid and sustained multi-receptor surface loss with picomolar degradation potency, reaching near-maximal depletion within approximately 1.5 hours. Conjugation of Tritazumab to MMAE preserved receptor binding and produced substantially greater antiproliferative activity and improved tumor selectivity relative to clinical ADCs in matched cell models, along with potent o tumor growth inhibition and acceptable tolerability in a xenograft model. Extending the platform beyond cytotoxic payloads, a BRD4 molecular glue conjugate improved the selectivity window by > 100-fold and showed marked efficacy, while an EZH2-targeting PROTAC conjugate achieved an approximately 1,000-fold increase in intracellular degradation potency relative to the free PROTAC. These findings establish MINDS as a modular multispecific degrader-payload platform that integrates receptor co-depletion to enhance anticancer selectivity and efficacy. - Source: PubMed
Publication date: 2026/05/06
Kabir MdKim Yong Joon JeffreyDeng ZhijieXiang YufeiSargunas Paul RSong NuoziWang ZishanParam Nesteene JJin ChangzhongSang ZheYue AliciaBundo AlbaHossain RazeenZhong YueLin YindanXiong YanGuccione ErnestoHuang Kuan-LinFeng MingyeJin JianShi Yi