ArticleMedComm2024
A novel small molecule ZYZ384 targeting SMYD3 for hepatocellular carcinoma via reducing H3K4 trimethylation of the Rac1 promoter.
Article in MedComm, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Predictive bioactivity modeling and structural binding analysis for the identification of potential SMYD3 modulators.Molecular diversity · 2026Article
- Protein modification systems as cancer biomarkers and therapeutic targets.Precision clinical medicine · 2026Review
- A novel molecule ZYZ329 targeting histone methyltransferase SMYD3 suppresses pathological angiogenesis via the driven mitochondrial ROS/HIF-1α/VEGFA axis.Journal of translational medicine · 2026Article
- SMYD3-CDCP1 Axis Drives EMT and CAF Activation in Colorectal Cancer and Is Targetable for Oxaliplatin Sensitization.Biomedicines · 2025Article
- Canonical and Non-Canonical Functions of Histone H3K4 Methylation Modifiers in Cancer.Cancer science · 2025Review
- Small molecule compound ZYZ-384 targets SMYD3 to alleviate aging.Scientific reports · 2025Article
- Single-cell profiling of SLC family transporters: uncovering the role of SLC7A1 in osteosarcoma.Journal of translational medicine · 2025Article
- NRF1-Induced lncRNA DDX11-AS1 Contributes to the Progression of Hepatocellular Carcinoma via Activating CA9 Expression and the MEK/ERK Pathway.Journal of hepatocellular carcinoma · 2025Article
- Article
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SMYD3 (SET and MYND domain-containing 3) is a histone lysine methyltransferase highly expressed in different types of cancer(s) and is a promising epigenetic target for developing novel antitumor therapeutics. No selective inhibitors for this protein have been developed for cancer treatment. Therefore, the current study describes developing and characterizing a novel small molecule ZYZ384 screened and synthesized based on SMYD3 structure. Virtual screening was initially used to identify a lead compound and followed up by modification to get the novel molecules. Several technologies were used to facilitate compound screening about these novel molecules' binding affinities and inhibition activities with SMYD3 protein; the antitumor activity has been assessed in vitro using various cancer cell lines. In addition, a tumor-bearing nude mice model was established, and the activity of the selected molecule was determined in vivo. Both RNA-seq and chip-seq were performed to explore the antitumor mechanism. This work identified a novel small molecule ZYZ384 targeting SMYD3 with antitumor activity and impaired hepatocellular carcinoma tumor growth by reducing H3K4 trimethylation of the Rac1 promoter triggering the tumor cell cycle arrest through the AKT pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.