GSK1379725A (AU1)

The first selective inhibitor of BPTF over Brd4

Core Function

• Selective inhibitor/ligand of BPTF (bromodomain PHD finger transcription factor)
• Binds to the bromodomain of BPTF with moderate affinity (~Kd ≈ 2.8 µM)
• Shows high selectivity vs. BRD4 (little to no binding)

Mechanism of Action

• BPTF is part of the NURF chromatin remodeling complex, which regulates gene expression.
• GSK1379725A: 
• - Occupies the acetyl-lysine binding pocket of BPTF
• - Prevents BPTF from binding to acetylated histones
• - Disrupts recruitment of the NURF complex to chromatin
• Result:
  • - Alters chromatin accessibility
  • - Changes gene transcription programs

Biological Effects (Research Findings)

1. Anti-cancer activity

• Inhibits proliferation of cancer cells (e.g., breast cancer, leukemia)
• Reduces tumor growth and metastasis in animal models

2. Chemosensitization

• Enhances the effectiveness of chemotherapy drugs
• Can:
  • - Increase apoptosis (cell death)
  • - Induce senescence
  • - Interfere with drug resistance mechanisms (e.g., P-gp efflux pump)

3. Epigenetic modulation

• Acts as a tool compound to study:
  • - Chromatin remodeling
  • - Transcriptional regulation
  • - Role of BPTF in disease

0°C (short term), -20°C (long term), desiccated