University of Kentucky Background
The breast cancer therapeutics market size is $17 billion (as of 2017), growing at a CAGR of 10.7%. The development of novel therapies to eliminate aggressive breast cancer is an unmet need. Over 50% of cancer patients receive platinum agents worldwide. Although platinum is effective in certain types of cancer like bladder and testicular cancer, its response rate in other types of cancer is stymied by recurrence due to acquired and innate mechanisms. The discovery of new transition metal complexes with new targets/mechanism of action have become alternate strategies to improve treatment outcomes.
Gold-based probe development and drug discovery remain a flourishing area of biological research and treatment for various diseases, including cancer, following the FDA approval of auranofin to treat rheumatoid arthritis. The excellent safety profile of gold makes it an attractive metal to develop small-molecule compounds. Metabolic programming and increased mitochondrial activity play an important role in pathologies of several diseases including cancer. Agents targeting mitochondrial respiration will yield transformative clinical benefit for several pathological conditions including cancer. Novel gold-based scaffolds that preferentially target mitochondria and possess multifaceted target mechanisms to avoid resistance will be particularly useful.
UK researchers have developed novel gold-based compounds to treat cancer. The series of gold compounds selectively target mitochondrial respiration to treat aggressive disease. These compounds irreversibly modulate respiration with high selectivity for cancer cells or highly inflamed cells. In the context of cancer, mechanism-of-action (MOA) of the new gold-based lead candidates are uniquely different from cisplatin, which induces DNA cross-links. The gold compounds exploit mitochondrial oxidative phosphorylation and cellular energy mechanisms to promote cancer cell-selective cell death, while sparing healthy cells. This innovative approach has been applied to inhibit growth and metastasis of aggressive breast cancer.
Kim JH, Reeder E, Parkin S, Awuah SG. Gold(I/III)-Phosphine Complexes as Potent Antiproliferative Agents. Sci Rep. 2019 Aug 26;9(1):12335. doi: 10.1038/s41598-019-48584-5. PMID: 31451718; PMCID: PMC6710276.
Awuah SG, Ofori S, Gukathasan S. Gold-Based Pharmacophore Inhibits Intracellular MYC Protein. Chemistry. 2020 Dec 4. doi: 10.1002/chem.202004962. Epub ahead of print. PMID: 33275307
Stage of Development
Ongoing mice studies.
High selectivity for cancer cells over normal cells (30-fold)
High cellular uptake in cancer cells; high cytotoxicity in various cancer cell lines
Safer than other currently available small molecule organic- or platinum-based options
Changing ligands allows targeting of different mitochondrial dynamics
Better safety without immunocompromise compared to auranofin
Treatment of cancer
Other potential therapeutic areas:
Treatment of Inflammatory Bowel Disease