Synthesis of NVS-BPTF-1 and evaluation of its biological activity

Bioorg Med Chem Lett. 2021 Sep 1:47:128208. doi: 10.1016/j.bmcl.2021.128208. Epub 2021 Jun 16.

Abstract

BPTF (bromodomain and PHD finger containing transcription factor) is a multidomain protein that plays essential roles in transcriptional regulation, T-cell homeostasis and stem cell pluripotency. As part of the chromatin remodeling complex hNURF (nucleosome remodeling factor), BPTF epigenetic reader subunits are particularly important for BPTF cellular function. Here we report the synthesis of NVS-BPTF-1, a previously reported highly potent and selective BPTF-bromodomain inhibitor. Evaluation of the impact of the inhibition of BPTF-bromodomain using NVS-BPTF-1 on selected proteins involved in the antigen processing pathway revealed that exclusively targeting BPTF-bromodomain is insufficient to observe an increase of PSMB8, PSMB9, TAP1 and TAP2 proteins.

Keywords: BPTF; NURF; NVS-BPTF-1; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Nuclear
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Nerve Tissue Proteins / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Transcription Factors / antagonists & inhibitors*

Substances

  • Antigens, Nuclear
  • Nerve Tissue Proteins
  • Transcription Factors
  • fetal Alzheimer antigen