Induction of apoptosis in MDA-MB-231 breast cancer cells by a PARP1-targeting PROTAC small molecule

Chem Commun (Camb). 2019 Jan 2;55(3):369-372. doi: 10.1039/c8cc07813k.

Abstract

Poly (ADP-ribose) polymerase-1 (PARP1) is a major member of the PARP superfamily that is involved in DNA damage signalling and other important cellular processes. Here we report the development of a small molecule targeting PARP1 based on the PROTAC strategy. In the MDA-MB-231 cell line, the representative compound 3 can induce significant PARP1 cleavage and programmed cell death.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • DNA Damage
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Molecular Structure
  • Piperidines / chemical synthesis
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Poly (ADP-Ribose) Polymerase-1 / antagonists & inhibitors*
  • Poly (ADP-Ribose) Polymerase-1 / metabolism
  • Poly(ADP-ribose) Polymerase Inhibitors / chemical synthesis
  • Poly(ADP-ribose) Polymerase Inhibitors / chemistry
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology*
  • Proteolysis
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Piperidines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Small Molecule Libraries
  • piperidine
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1