Enhanced Cell-potent Inhibitors for NTMT1/2 for Treating Cancers

Technology Readiness Level: 2Technology Validation: In vitro cytotoxicity studies were conducted in normal and NTMT1 knock-out HCT116 cells.
  • Technology Readiness Level: 2
  • Technology Validation: In vitro cytotoxicity studies were conducted in normal and NTMT1 knock-out HCT116 cells.

Abstract

Researchers at Purdue University have designed a series of new peptidomimetic inhibitors for protein alpha-N-terminal methyltransferases (NTMTs). NTMTs recognize a unique N-terminal of a protein and catalyze the addition of 1-3 methyl group(s) to it. The exact role and function of NTMTs is unknown, but NTMT1 plays an important role in mitosis, DNA damage repair, stem cell maintenance, glioblastoma, and cervical cell proliferation and migration. NTMT1 is a potential anti-cancer target as it is overexpressed in several cancers such as gastrointestinal, colorectal and melanoma. To improve the cellular inhibition activity of previously invented peptidomimetic inhibitors, the Purdue researchers designed several cell-potent peptidomimetic inhibitors of N-terminal methylation. These inhibitors displayed not only increased cellular inhibition, but they were also optimized for increased hydrophobicity which co-relates with increased cell permeability. The most potent inhibitor (IC50 = 0.9 uM) exhibited over 2-fold increased inhibition on cellular N-terminal methylation levels with a cellular IC50 value of ~50 µM compared to previously reported peptidomimetic inhibitors of NTMT1. It also exhibited over 300-fold selectivity to several other methyltransferases. These cell-potent inhibitors serve as valuable tools to study the function and role of NTMTs and the alpha-N-terminal methylation pathway in cancer and stem cell maintenance.

Website

https://prf.flintbox.com/technologies/6C58C231B0FB46098638A9086D43F516

Advantages

  • Fully characterized in biochemical and biophysical methods
  • Highly effective inhibition of N-terminal methylation
  • High selectivity to a panel of methyltransferases

Potential Applications

  • Novel cancer treatment for cervical cancer and glioblastoma
  • Stem cell therapy
  • Studying NTMTs and the alpha-N-terminal methylation pathway

Contact Information

Name: Ayantika Ghosh-Bhattacharjee

Email: aghoshbh@purdue.edu

Phone: 765-588-3825