Related Experiment Video

Updated: Jun 19, 2026

Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells
08:11

Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells

Published on: August 7, 2021

Unique Cysteine-Directed Covalent Inhibition of PRMT1 Suppresses Breast Tumorigenesis

Min Shao1, Ruining Li1, Jinglei Hu1

  • 1Shanghai Frontiers Science Center of Targeted Drugs, State Key Laboratory of Innovative Immunotherapy, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Engineering Research Center of Cell & Therapeutic Antibody Ministry of Education, School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.

Journal of Medicinal Chemistry
|June 17, 2026
PubMed

Insights

A novel covalent inhibitor, 17zh, selectively targets PRMT1, an enzyme linked to breast cancer. This compound demonstrated significant efficacy in preclinical models, offering a promising new avenue for epigenetic cancer therapy.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Oncology

Background:

  • Protein arginine methyltransferase 1 (PRMT1) dysregulation is crucial in breast cancer development.
  • Developing selective PRMT1 inhibitors is difficult due to conserved catalytic domains among PRMT family members.

Purpose of the Study:

  • To develop and characterize a novel, selective small-molecule inhibitor for PRMT1.
  • To evaluate the therapeutic potential of this inhibitor in breast cancer models.

Main Methods:

  • Design and synthesis of a covalent inhibitor, 17zh (MS3-123), targeting PRMT1's unique Cys119 residue.
  • Enzymatic and cellular assays to determine PRMT1 inhibition and selectivity.
  • In vitro and in vivo studies using breast cancer cell lines and xenograft models to assess anti-cancer effects.

Main Results:

  • 17zh demonstrated potent and selective nanomolar inhibition of PRMT1 (IC50 = 11.4 nM), with significant selectivity over other PRMTs.
  • 17zh effectively inhibited PRMT1 activity in enzymatic and cellular contexts.
  • The compound suppressed breast cancer cell proliferation, migration, invasion, induced apoptosis and cell cycle arrest, and reduced tumor growth in vivo.

Conclusions:

  • 17zh is the first selective covalent inhibitor of PRMT1, validated as a potent chemical probe.
  • 17zh shows significant promise as a lead compound for breast cancer treatment, validating covalent targeting for epigenetic drug discovery.

More Related Videos

Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module10:39

Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module

Published on: June 18, 2015

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.