Licensing status

Publication and contact information



Breast cancer 1 early onset (BRCA1)

In vitro studies have identified cell-penetrant phospho-dipeptide inhibitors of the BRCT domain of BRCA1 that could be useful for treating cancer. A microarray-based in vitro screen for compounds that could inhibit protein-protein interactions involving the phosphoserine-binding BRCT domain of BRCA1 identified a competitive phospho-dipeptide inhibitor with an IC50 value of
0.31 mM that could also penetrate cells. In a human cancer cell line, the phospho-dipeptide and nonhydrolyzable or prodrug variants increased apoptosis compared with vehicle and caused synergistic increases in cell killing when combined with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib. Ongoing work includes improving the compound's in vivo activity and solving the crystal structure of the lead dipeptide inhibitor in complex with BRCA1.
AstraZeneca plc has olaparib under FDA and EMA review to treat ovarian cancer.

SciBX 7(29); doi:10.1038/scibx.2014.857
Published online July 31, 2014

Unpatented; licensing status not applicable

Na, Z. et al. Angew. Chem. Int. Ed.; published online June 24, 2014;
Contact: Shao Q. Yao, National University of Singapore, Singapore