ArticleOrganic & biomolecular chemistry2015
Design, synthesis, and kinetic analysis of potent protein N-terminal methyltransferase 1 inhibitors.
Article in Organic & biomolecular chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 56 citations in OpenAlex.
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- Development of Efficient Covalent Inactivators of a Fungal Aspartate Semialdehyde Dehydrogenase.Drug development research · 2025Article
- Article
- Structure-Activity Relationship Studies of Venglustat on NTMT1 Inhibition.Journal of medicinal chemistry · 2023Article
- Design and characterization of PROTAC degraders specific to protein N-terminal methyltransferase 1.European journal of medicinal chemistry · 2022Article
- Venglustat Inhibits Protein N-Terminal Methyltransferase 1 in a Substrate-Competitive Manner.Journal of medicinal chemistry · 2022Article
- Methyltransferases: Functions and Applications.Chembiochem : a European journal of chemical biology · 2022Review
- Turning Nonselective Inhibitors of Type I Protein Arginine Methyltransferases into Potent and Selective Inhibitors of Protein Arginine Methyltransferase 4 through a Deconstruction-Reconstruction and Fragment-Growing Approach.Journal of medicinal chemistry · 2022Article
- Synthesis and Activity of Triazole-Adenosine Analogs as Protein Arginine Methyltransferase 5 Inhibitors.Molecules (Basel, Switzerland) · 2022Article
- Knockdown of NRMT enhances sensitivity of retinoblastoma cells to cisplatin through upregulation of the CENPA/Myc/Bcl2 axis.Cell death discovery · 2022Article
- Discovery of a potent and dual-selective bisubstrate inhibitor for protein arginine methyltransferase 4/5.Acta pharmaceutica Sinica. B · 2021Article
- Past, present, and perspectives of protein N-terminal methylation.Current opinion in chemical biology · 2021Review
- Multi-omics integration of methyltransferase-like protein family reveals clinical outcomes and functional signatures in human cancer.Scientific reports · 2021Article
- Chemoproteomic Study Uncovers HemK2/KMT9 As a New Target for NTMT1 Bisubstrate Inhibitors.ACS chemical biology · 2021Article
- Structure-based Discovery of Cell-Potent Peptidomimetic Inhibitors for Protein N-Terminal Methyltransferase 1.ACS medicinal chemistry letters · 2021Article
- Selective Peptidomimetic Inhibitors of NTMT1/2: Rational Design, Synthesis, Characterization, and Crystallographic Studies.Journal of medicinal chemistry · 2020Article
- Probing the Plasticity in the Active Site of Protein N-terminal Methyltransferase 1 Using Bisubstrate Analogues.Journal of medicinal chemistry · 2020Article
- Optimization of High-Throughput Methyltransferase Assays for the Discovery of Small Molecule Inhibitors.ACS combinatorial science · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The protein N-terminal methyltransferase 1 (NTMT1) methylates the α-N-terminal amines of proteins. NTMT1 is upregulated in a variety of cancers and knockdown of NTMT1 results in cell mitotic defects. Therefore, NTMT1 inhibitors could be potential anticancer therapeutics. This study describes the design and synthesis of the first inhibitor targeting NTMT1. A novel bisubstrate analogue (NAM-TZ-SPKRIA) was shown to be a potent inhibitor (Ki = 0.20 μM) for NTMT1 and was selective versus protein lysine methyltransferase G9a and arginine methyltransferase 1. NAM-TZ-SPKRIA was found to exhibit a competitive inhibition pattern for both substrates, and mass spectrometry experiments revealed that the inhibitor substantially suppressed the methylation progression. Our results demonstrate the feasibility of using a triazole group to link an S-adenosyl-L-methionine analog with a peptide substrate to construct bisubstrate analogues as NTMT1 potent and selective inhibitors. This study lays a foundation to further discover small molecule NTMT1 inhibitors to interrogate its biological functions, and suggests a general strategy for the development of selective protein methyltransferase inhibitors.
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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 OpenQuestion graph.